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Sanofi’s Dupixent® approved for children aged 6 to 11 years with severe asthma

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Sanofi’s Dupixent® approved for children aged 6 to 11 years with severe asthma

April 7, 2022: “The EC has expanded the marketing authorization for Dupixent® (dupilumab) in the European Union.

Dupixent is now also approved in children aged 6 to 11 years as an add-on maintenance treatment for severe asthma with type 2 inflammation characterized by raised blood eosinophils and/or raised fractional exhaled nitric oxide (FeNO), who are inadequately controlled with medium to high dose inhaled corticosteroids (ICS) plus another medicinal product for maintenance treatment.

Naimish Patel, M.D.
Head of Global Development, Immunology and Inflammation, Sanofi
 “We are excited to bring the well-established safety and efficacy of Dupixent to even younger patients living with uncontrolled severe asthma in Europe.

In addition to greatly reducing severe asthma attacks and improving lung function, patients in our clinical trial also reduced their oral corticosteroid use.

This is particularly meaningful as these are medicines that can carry significant safety risks if used long term.

This approval underscores our continued commitment to bringing Dupixent to as many patients as possible suffering from the negative effects of severe asthma with the hope of improving their quality of life.”

Asthma is one of the most common chronic diseases in children. Up to 85% of children with asthma may have type 2 inflammation and are more likely to have higher disease burden.

Despite treatment with current standard-of-care ICS and bronchodilators, these children may continue to experience serious symptoms such as coughing, wheezing and difficulty breathing.

Severe asthma may impact children’s developing airways and cause potentially life-threatening exacerbations.

Children with severe asthma also may require the use of multiple courses of systemic corticosteroids that carry significant risks. Uncontrolled severe asthma can interfere with day-to-day activities, like sleeping, attending school and playing sports.

Dupixent is a fully human monoclonal antibody that inhibits the signaling of the interleukin-4 (IL-4) and interleukin-13 (IL-13) pathways and is not an immunosuppressant.

The Dupixent Phase 3 clinical program, which has shown significant clinical benefit and a decrease in type 2 inflammation, has established that IL-4 and IL-13 are key and central drivers of the type 2 inflammation that plays a major role in in multiple related and often co-morbid diseases.

George D. Yancopoulos, M.D., Ph.D.
President and Chief Scientific Officer, Regeneron
 “Today’s approval in Europe recognizes the benefits of Dupixent in helping children living with the profound effects of severe asthma, including unpredictable asthma attacks, routine disruption to daily activities and the use of systemic steroids that can impede children’s growth. 

Dupixent is the only treatment available that specifically blocks two key drivers of type 2 inflammation, IL-4 and IL-13, which our trials show plays a major role in childhood asthma, as well as in related conditions such as chronic rhinosinusitis with nasal polyposis and the often co-morbid condition, atopic dermatitis.

In clinical trials, Dupixent significantly reduced asthma attacks, helped children breathe better and improved their health-related quality of life. We also remain committed to investigating Dupixent in other conditions where type 2 inflammation may significantly impact patients’ lives, including eosinophilic esophagitis, prurigo nodularis and chronic spontaneous urticaria.”

The EC decision is based on pivotal data from the Phase 3 VOYAGE trial evaluating the efficacy and safety of Dupixent combined with standard-of-care asthma therapy in 408 children with uncontrolled moderate-to-severe asthma.

Two pre-specified populations with evidence of type 2 inflammation were evaluated for the primary analysis: 1) patients with baseline blood eosinophils (EOS) ≥300 cells/μl (n=259) and 2) patients with either baseline FeNO ≥20 parts per billion (ppb) or baseline blood EOS ≥150 cells/μl (n=350).

Patients who added Dupixent to standard-of-care in these two groups, respectively, experienced:

  • Substantially reduced rates of severe asthma attacks, with a 65% and 59% average reduction over one year compared to placebo (0.24 and 0.31 events per year for Dupixent vs. 0.67 and 0.75 for placebo, respectively).
  • Improved lung function observed as early as two weeks and sustained for up to 52 weeks, measured by percent predicted FEV1 (FEV1pp).
    • At 12 weeks, patients taking Dupixent improved their lung function by 5.32 and 5.21 percentage points compared to placebo, respectively.
  • Improved asthma control, with 81% and 79% of patients reporting a clinically meaningful improvement at 24 weeks, based on disease symptoms and impact compared to 64% and 69% of placebo patients, respectively.
  • Improved health-related quality of life, with 73% and 73% of patients reporting a clinically meaningful improvement at 24 weeks, compared to 63% and 65% of placebo patients, respectively.
  • Reduced systemic corticosteroid use by an average of 66% and 59% over one year compared to placebo (0.27 and 0.35 courses per year for Dupixent vs. 0.81 and 0.86 for placebo, respectively).

The safety results from the trial were generally consistent with the known safety profile of Dupixent in patients aged 12 years and older with uncontrolled moderate-to-severe asthma.

The overall rates of adverse events were 83% for Dupixent and 80% for placebo.

Adverse events that were more commonly observed with Dupixent compared to placebo included injection site reactions (18% Dupixent, 13% placebo), viral upper respiratory tract infections (12% Dupixent, 10% placebo) and eosinophilia (7% Dupixent, 1% placebo).

Helminth infections were also more commonly observed with Dupixent in patients aged 6 to 11 years and were reported in 2% of Dupixent patients and 0% of placebo patients.

About the LIBERTY ASTHMA VOYAGE Trial

The Phase 3 randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of Dupixent (100 mg or 200 mg every two weeks, based on weight tier) combined with standard-of-care asthma therapy in 408 children aged 6 to 11 years with uncontrolled moderate-to-severe asthma.

More than 90% of children in the trial had at least one concurrent atopic medical condition such as allergic rhinitis and atopic dermatitis.

The primary endpoint was the annualized rate of severe asthma exacerbations over one year, and the key secondary endpoint was the change from baseline in percentage of predicted pre-bronchodilator FEV1 (FEV1pp) at week 12.

The FEV1pp seeks to evaluate a patient’s change in lung function compared to their predicted lung function based on age, height, sex and ethnicity to account for children’s growing lung capacity at different stages of development.

Additional secondary endpoints included responder rates for asthma control as measured by a ≥0.5 improvement on the Asthma Control Questionnaire-7 Interviewer Administered (ACQ-7-IA; 7-point scale) and health-related quality of life as measured by a ≥0.5 improvement on the Pediatric Asthma Quality of Life Questionnaire with Standardized Activities-Interviewer Administered (PAQLQ(S)-IA; 7-point scale).”

https://www.sanofi.com/en/media-room/press-releases/2022/2022-04-07-07-00-00-2418107

Pfizer to Acquire ReViral and Its Respiratory Syncytial Virus Therapeutic Candidates

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Pfizer to Acquire ReViral and Its Respiratory Syncytial Virus Therapeutic Candidates

April 07, 2022: “Pfizer Inc. and ReViral Ltd. announced that the companies have entered into a definitive agreement under which Pfizer will acquire ReViral, a privately held, clinical-stage biopharmaceutical company focused on discovering, developing, and commercializing novel antiviral therapeutics that target respiratory syncytial virus (RSV).

“At Pfizer, we have a strong heritage in, and commitment to, fighting infectious diseases, most recently evidenced by our delivery of the first authorized vaccine and oral therapy to combat COVID-19,” said Albert Bourla, Chairman and Chief Executive Officer, Pfizer.

“We’re continuing to grow our pipeline – through our own research-and-development efforts, such as our investigational RSV vaccine programs, as well as strategic investments in companies like ReViral – with a focus on end-to-end capabilities to help protect patients from severe illness, hospitalization, and death.”

RSV is a respiratory pathogen, which can lead to severe and life-threatening lower respiratory tract infections (LRTIs) in high-risk populations, including young infants, immunocompromised individuals, and older adults. It is estimated to cause infections in approximately 64 million people, resulting in about 160,000 deaths, globally each year.

ReViral has a portfolio of promising therapeutic candidates, including sisunatovir, an orally administered inhibitor designed to block fusion of the RSV virus to the host cell.

Sisunatovir significantly reduced viral load in a phase 2 RSV human challenge study in healthy adults and is currently in phase 2 clinical development in infants.

The development program for sisunatovir is expected to continue in both adult and pediatric populations.

A second program is focused on the inhibition of RSV replication targeting the viral N protein.

The lead candidate in this program is currently in phase 1 clinical development.

“Currently, treatment options for RSV are extremely limited and focus primarily on supportive care,” said Annaliesa Anderson, Ph.D., Senior Vice President and Chief Scientific Officer, Bacterial Vaccines and Hospital, at Pfizer.

“The proposed acquisition of ReViral’s pipeline of therapeutic candidates is complementary to our efforts to advance the first vaccine candidate to help protect against this harmful disease.

Combining the capabilities and expertise of our organizations will enable us to further the clinical development of a potential therapy for those with RSV disease.”

Sisunatovir has been granted Fast Track designation by the U.S. Food and Drug Administration (FDA). In June 2021,

ReViral announced the successful completion of Part A of the phase 2 REVIRAL1 study of sisunatovir for the treatment of RSV infections in hospitalized infants.

REVIRAL1 is a global three-part adaptive study to evaluate the safety, tolerability, pharmacokinetic (PK) profile, antiviral effects, and clinical effect of single and multiple oral doses of sisunatovir in otherwise healthy infants between the ages of 1 and 36 months hospitalized with RSV LRTIs.

Following a thorough review by the REVIRAL1 Data Safety Monitoring Committee, sisunatovir showed a favorable safety and PK exposure profile to advance to Part B, the double-blind, placebo-controlled stage of the study where patients receive drug or placebo twice a day for five days.

“Since the foundation of the company a decade ago by Dr. Ken Powell and Dr. Stuart Cockerill, ReViral’s mission has always been to develop world-class therapies for RSV patients,” said Alex C. Sapir, CEO, ReViral.

“This acquisition represents a validation of the deep antiviral experience of the ReViral team and our unwavering commitment to deliver therapies for patients in need.

Pfizer is an optimal partner given their commitment to RSV through their ongoing RSV vaccine program, coupled with their world-class clinical, regulatory, manufacturing and commercial capabilities.

We look forward to working with our colleagues at Pfizer to bring these therapies to patients as quickly as possible.”

Under the terms of the agreement, Pfizer will acquire ReViral for a total consideration of up to $525 million, including upfront and development milestones.

If successful, Pfizer believes annual revenue for these programs has the potential to reach or exceed $1.5 billion.

The proposed transaction is subject to customary closing conditions, including receipt of regulatory approvals.

Clifford Chance LLP is acting as Pfizer’s legal advisor.

Centerview Partners LLC and BofA Securities served as ReViral’s financial advisors, with Goodwin Procter LLP acting as its legal advisor.

About ReViral

ReViral is a clinical-stage biopharmaceutical company focused on discovering, developing, and commercializing antiviral therapeutics, with an initial focus on treating respiratory syncytial virus (RSV).

The company’s lead product candidate, sisunatovir, is an orally administered fusion inhibitor currently being evaluated in a global phase 2 pediatric clinical study (REVIRAL1).

The company also has an RSV N-protein replication inhibitor program currently in phase 1 clinical development.”

Novartis announces tislelizumab for regulatory review in esophageal and lung cancers

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April 6, 2022: “Novartis announced that the EMA validated Marketing Authorization Applications (MAAs) for the immune checkpoint inhibitor tislelizumab for adults with:

  • Locally advanced or metastatic, squamous or non-squamous non-small cell lung cancer (NSCLC) as first-line treatment in combination with chemotherapy,
  • Locally advanced or metastatic NSCLC as monotherapy after prior chemotherapy, and
  • Unresectable, recurrent, locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) as monotherapy after prior chemotherapy.

Tislelizumab is a humanized IgG4 anti-PD-1 monoclonal antibody being developed both as a monotherapy and in combination with other therapies.

“This is an important step toward expanding treatment options for cancer patients in Europe, and builds on the US FDA filing acceptance for tislelizumab in esophageal cancer,” said Jeff Legos, Executive Vice President, Global Head of Oncology & Hematology Development.

“We look forward to working with the EMA to make tislelizumab available to people with these aggressive cancers, while continuing to expand our development program to investigate the potential of novel, synergistic combinations.”

The MAAs include data from the pivotal Phase III RATIONALE 302 trial, in which tislelizumab demonstrated a significant improvement in overall survival versus chemotherapy as treatment for people with ESCC who had received prior chemotherapy.

The submissions also include data from the pivotal Phase III RATIONALE 303 trial, which showed tislelizumab significantly improved overall survival versus chemotherapy in people with NSCLC after treatment with chemotherapy, and from RATIONALE 304 and 307, which showed tislelizumab plus chemotherapy significantly improved progression-free survival versus chemotherapy in people with untreated squamous and non-squamous NSCLC.

Lung cancer is one of the most common cancers worldwide, accounting for more than 2 million new cases diagnosed each year.

More people die of lung cancer every year than any other cancer.

ESCC is the most common type of esophageal cancer globally, with an estimated 604,000 new cases and 544,000 deaths from esophageal cancer internationally in 2020.

About RATIONALE Trials
RATIONALE 302 (NCT03430843) is a multi-regional, open-label, randomized Phase III study of tislelizumab versus chemotherapy in patients with advanced unresectable/metastatic esophageal squamous cell carcinoma who had received prior systemic therapy.

Approximately 513 patients were randomized 1:1 to receive tislelizumab or investigator chosen chemotherapy.

The primary endpoint is overall survival (OS); the key secondary endpoint was OS in the PD-L1 positive population. Other secondary endpoints include progression-free survival (PFS), objective response rate (ORR), duration of response (DoR), health-related quality of life measures and safety.

RATIONALE 303 (NCT03358875) is a multi-regional, open-label, multicenter, randomized Phase III study of tislelizumab versus chemotherapy in patients with locally advanced or metastatic NSCLC who have progressed on a prior platinum-containing regimen.

Approximately 805 patients were randomized 1:1 to receive tislelizumab or chemotherapy.

The co-primary endpoints are OS in all patients and OS in PD-L1 positive patients. Secondary endpoints include PFS, ORR, DoR, health-related quality of life measures and safety.

RATIONALE 304 (NCT03663205) is an open-label, multicenter, randomized Phase III study of tislelizumab plus chemotherapy versus chemotherapy alone in patients with untreated advanced non-squamous NSCLC.

Approximately 334 patients were randomized 1:1 to receive either tislelizumab plus chemotherapy or chemotherapy. The primary endpoint is PFS. Secondary endpoints include OS, ORR, DoR, health-related quality of life measures and safety.

RATIONALE 307 (NCT03594747) is an open-label, multicenter, randomized Phase III study of tislelizumab plus chemotherapy versus chemotherapy in patients with untreated advanced squamous NSCLC.

Approximately 360 patients were randomized 1:1:1 to receive tislelizumab plus paclitaxel, tislelizumab plus nab-paclitaxel, or chemotherapy alone.

The primary endpoint is PFS. Secondary endpoints include OS, ORR, DoR, health-related quality of life measures and safety.

About Tislelizumab
Novartis is evaluating tislelizumab, a uniquely designed anti-PD-1 monoclonal antibody, in a global clinical development program consisting of 14 pivotal clinical trials across a broad array of solid tumors, with more than 8,800 patients enrolled to date in 35 countries.

Novartis four distinct therapeutic platforms (immunotherapy, radioligand therapy, cell and gene therapy, targeted therapy) offer a unique opportunity to study tislelizumab in differentiated, potentially synergistic combinations across our pipeline and portfolio of market compounds.

Novartis has the rights to develop, manufacture and commercialize tislelizumab in North America, Europe and Japan through a collaboration and license agreement with BeiGene.”

https://www.novartis.com/news/media-releases/novartis-announces-anti-pd-1-tislelizumab-accepted-ema-regulatory-review-esophageal-and-lung-cancers

Gilead’s Yescarta Approved for Treatment of Relapsed or Refractory LBCL

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Gilead’s Yescarta Approved for Treatment of Relapsed or Refractory LBCL

April 01, 2022: “Kite, a Gilead Company announced the U.S. FDA has approved Yescarta® (axicabtagene ciloleucel) CAR T-cell therapy for adult patients with large B-cell lymphoma that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy.

Yescarta demonstrated a clinically meaningful and statistically significant improvement in event-free survival (EFS; hazard ratio 0.398; P< 0.0001) over the current standard of care (SOC) that has been in place for decades.

EFS was determined by blinded central review and defined as the time from randomization to the earliest date of disease progression, commencement of new lymphoma therapy, or death from any cause.

Additionally, 2.5 times more patients receiving Yescarta (40.5%) were alive at two years without disease progression or need for additional cancer treatment, after their one-time infusion of Yescarta vs. SOC (16.3%), and the median EFS was four-fold greater (8.3 months vs. 2.0 months) with Yescarta vs. SOC.

Yescarta is also being reviewed by global regulatory authorities for additional indications inclusive of the ZUMA-7 patient population.

ZUMA-7 is considered a landmark trial for being the first and largest trial of its kind, with the longest follow-up.

Earlier this month, the National Comprehensive Cancer Network (NCCN) updated its Clinical Practice Guidelines in Oncology for B-cell Lymphomas to include Yescarta for “Relapsed disease <12 mo or Primary Refractory disease” under Diffuse Large B-cell Lymphoma (DLBCL) as a Category 1 recommendation.

Yescarta is the first CAR T-cell therapy to receive a NCCN Category 1 recommendation.

NCCN defines Category 1 as recommendations based upon high-level evidence with uniform NCCN consensus that the intervention is appropriate.

Christi Shaw, Chief Executive Officer of Kite: “Kite started with a very bold goal: creating the hope of survival through cell therapy. Today’s FDA approval brings that hope to more patients by enabling the power of CAR T-cell therapy to be used earlier in the treatment journey.

This milestone has been years in the making. On behalf of the entire Kite community, we would like to thank the patients and physicians who have been on this journey with us. You are what drives us every day to explore the full potential of cell therapy.”

CAR T-cell therapies are individually made starting from a patient’s own white blood cells, called T-cells.

The cells are removed through a process similar to donating blood and sent to Kite’s specialized manufacturing facilities where they are engineered to target the patient’s cancer, expanded, and then returned to the hospital for infusion back into the patient.

Referring physicians and patients can immediately begin accessing Yescarta CAR T-cell therapy for this new FDA-approved indication through Kite’s 112 authorized treatment centers across the U.S.

Frederick L. Locke, MD, ZUMA-7 Principal Investigator and Co-Leader of the Immuno-Oncology Program at Moffitt Cancer Center, Tampa, Florida: “Today’s approval marks an exciting new standard of care. The ZUMA-7 trial enabled us to look at the broader picture of what happens to patients after a decision is made to follow a particular treatment path.

What we found was that axi-cel resulted in three times as many patients receiving treatment with curative intent (CAR T-cell therapy), and an overall better outcome for patients than the previous standard of care.

Additionally, we have now amassed significant experience with CAR T-cell therapy to better manage or prevent side-effects, making this treatment more accessible for older patients and those with medical conditions for whom the standard of care might be difficult.”

SOC therapy for this patient population has historically been a multi-step process expected to end with a stem cell transplant.

The process starts with chemoimmunotherapy, and if a patient responds to and can tolerate further treatment, they move on to high-dose chemotherapy (HDT) followed by a stem cell transplant (ASCT).

Jason Westin, MD, MS, FACP, ZUMA-7 Principal Investigator, Director, Lymphoma Clinical Research, and Associate Professor, Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center: “Definitive clinical trial results such as these do not come along often and should drive a paradigm shift in how patients with relapsed or refractory LBCL are treated moving forward.

Patients who do not respond to or relapse after initial treatment should quickly be referred to a CAR T-cell therapy authorized treatment center for evaluation.”

Kite CAR T-cell therapy products are widely covered by commercial and government insurance programs in the U.S. Kite has also invested in expansion of manufacturing capacity ahead of today’s FDA decision to support patient access.

Lee Greenberger, PhD, Chief Scientific Officer of The Leukemia & Lymphoma Society (LLS): “LLS was an early supporter of CAR T-cell therapy research, and to be able to see this innovative advance become available as an earlier line of treatment is truly remarkable.

Current standard of care is a difficult process for patients, and no one knows at the start who will make it to stem cell transplant. With today’s FDA decision, patients will have earlier access to this potentially curative treatment.” ​

Yescarta was initially approved by the FDA in 2017 based on the ZUMA-1 trial for a smaller population of LBCL patients who failed two or more lines of therapy.

The ZUMA-1 trial has recently reported durable 5-year survival results, with Yescarta showing 42.6% of study patients alive at 5 years and that 92% of those patients alive at 5 years have needed no additional cancer treatment at this important milestone.

As the only company dedicated exclusively to the research, development, commercialization, and manufacturing of cell therapy on a global scale, Kite has all functions critical to cell therapy vertically integrated.

This structure enables the continual refinement and support of the highly specialized and complex end-to-end processes needed to support and improve upon patient outcomes with CAR T-cell therapy.

About ZUMA-7 Study

The FDA approval of Yescarta CAR T-cell therapy for adult patients with large B-cell lymphoma (LBCL) that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy is based on results from the ZUMA-7 study.

Patients had not yet received treatment for relapsed or refractory lymphoma and were potential candidates for autologous stem cell transplant (ASCT).

Results were presented in a Plenary session at the American Society of Hematology’s (ASH) Annual Meeting & Exposition in December 2021 and simultaneously published in the NewEngland Journal of Medicine (NEJM).

ZUMA-7 is a randomized, open-label, global, multicenter, Phase 3 study evaluating the safety and efficacy of Yescarta versus current standard of care (SOC) for second-line therapy (platinum-based salvage combination chemoimmunotherapy regimen followed by high-dose therapy [HDT] and ASCT in those who respond to salvage chemotherapy) in adult patients with relapsed or refractory LBCL within 12 months of first-line therapy.

In the study, 359 patients in 77 centers around the world were randomized (1:1) to receive a single infusion of Yescarta or current SOC second-line therapy.

The primary endpoint is event-free survival (EFS) as determined by blinded central review and defined as the time from randomization to the earliest date of disease progression per Lugano Classification, commencement of new lymphoma therapy, or death from any cause.

Key secondary endpoints include objective response rate (ORR) and overall survival (OS). Additional secondary endpoints include patient reported outcomes (PROs) and safety.

Yescarta demonstrated a 2.5-fold increase in patients who were alive at two years and did not experience cancer progression or require the need for additional cancer treatment (40.5% vs. 16.3%) and a four-fold greater median EFS (8.3 mo. vs. 2.0 mo.) compared to SOC (hazard ratio 0.398; 95% CI: 0.308-0.514, P<0.0001).

In addition to being the largest and longest study of its kind, ZUMA-7 study participants on the Yescarta arm did not receive additional bridging chemotherapy that could have potentially confounded results.

Nearly three times as many patients randomized to Yescarta ultimately received the definitive CAR T-cell therapy treatment (94%) versus those randomized to SOC (35%) who received on-protocol HDT+ASCT. More patients responded to Yescarta (ORR: 83% vs. 50%, odds ratio: 5.31 [95% CI: 3.1-8.9; P<0.0001) and achieved a complete response (CR) with Yescarta (CR rate: 65% vs. 32%) than with SOC.

At a pre-specified interim analysis at the time of the primary EFS analysis, OS has not met the criteria for statistical significance, but favored Yescarta.

Fifty-five percent of patients in the SOC arm subsequently received CD19-directed CAR T-cell therapy off study.

In the study, Yescarta had a safety profile that was consistent with previous studies. Among the 168 Yescarta-treated patients evaluable for safety, Grade ≥3 cytokine release syndrome (CRS) and neurologic events were observed in 7% and 25% of patients, respectively.

In the SOC arm, 83% of patients had high grade events, mostly cytopenias (low blood counts).

The Yescarta U.S. Prescribing Information has a BOXED WARNING for the risks of CRS and neurologic toxicities, and Yescarta is approved with a Risk Evaluation and Mitigation Strategy (REMS) due to these risks; see below for Important Safety Information.”

https://www.gilead.com/news-and-press/press-room/press-releases/2022/4/yescarta-receives-us-fda-approval-as-first-car-tcell-therapy-for-initial-treatment-of-relapsed-or-refractory-large-bcell-lymphoma-lbcl

BMS Receives EC Approval for Opdivo for recurrent or metastatic ESCC

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BMS Receives EC Approval for Opdivo for recurrent or metastatic ESCC

April 5, 2022: “Bristol Myers Squibb announced that the European Commission has approved Opdivo (nivolumab) in combination with fluoropyrimidine- and platinum-based chemotherapy for the first-line treatment of adult patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) with tumor cell PD-L1 expression ≥ 1%.

The EC’s decision is based on results from the Phase 3 CheckMate -648 trial, in which Opdivo with chemotherapy demonstrated a statistically significant and clinically meaningful overall survival (OS) benefit compared to chemotherapy alone at the pre-specified interim analysis.

The safety profile of Opdivo with chemotherapy was consistent with previously reported studies.

Results from CheckMate -648 were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in June 2021.

“This approval is an important advancement for patients in the EU, especially given the highly aggressive nature of advanced ESCC,” said Ian M. Waxman, M.D., development lead, gastrointestinal cancers, Bristol Myers Squibb.

“Opdivo with chemotherapy is now one of two newly approved Opdivo-based combinations to show superior overall survival benefit compared to chemotherapy alone, offering higher hopes for patients with unresectable advanced, recurrent or metastatic ESCC with tumor cell PD-L1 expression ≥ 1%.

We are eager to introduce this new treatment option to patients in the European Union and potentially improve their survival outcomes.”

The EC has also approved Opdivo in combination with Yervoy (ipilimumab) for the first-line treatment of adult patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) with tumor cell PD-L1 expression ≥ 1%.

The EC approval allows for the use of Opdivo with fluoropyrimidine- and platinum-based combination chemotherapy for the first-line treatment of adults with unresectable advanced, recurrent or metastatic ESCC with tumor cell PD-L1 expression ≥ 1% in the 27 member states of the European Union, as well as Iceland, Liechtenstein and Norway.

CheckMate -648 Efficacy and Safety Results

Results from CheckMate -648 include:

  • OS in participants with tumor cell PD-L1 expression ≥ 1%. (primary endpoint): Median OS was 15.44 months (95% Confidence Interval [CI]: 11.93, 19.52) for nivolumab with chemotherapy vs. 9.07 months (95% CI: 7.69, 9.95) for chemotherapy (Hazard Ratio [HR] = 0.54; 95% CI: 0.37, 0.80; p= <0.0001).
  • PFS in participants with tumor cell PD-L1 expression ≥ 1%. (primary endpoint): Median PFS was 6.93 months (95% CI: 5.68, 8.34) for nivolumab with chemotherapy vs. 4.44 months (95% CI: 2.89, 5.82) for chemotherapy (HR = 0.65; 95% CI: 0.46, 0.92; p=0.0023)
  • ORR (secondary endpoint): The ORR was 53.2% (95% CI: 45.1, 61.1) for nivolumab with chemotherapy vs. 19.7% (95% CI: 13.8, 26.8) for chemotherapy.
  • Safety (based on pooled data across tumor types): Incidence of Grade 3-5 adverse reactions was 76% for nivolumab with chemotherapy and 62% for chemotherapy alone, with 1.4% fatal adverse reactions attributed to nivolumab in combination with chemotherapy including pneumonia, febrile neutropenia, thrombosis, pneumonitis, diarrhea, and renal failure. Median duration of therapy was 6.44 months (95% CI: 5.95, 6.80) for nivolumab with chemotherapy and 4.34 months (95% CI: 4.04, 4.70) for chemotherapy.

About CheckMate -648

CheckMate -648 is a randomized Phase 3 study evaluating Opdivo plus Yervoy (N=325) or Opdivo with fluorouracil and cisplatin (N=321) against fluorouracil plus cisplatin alone (N=324) in patients with previously untreated, unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma.

The primary endpoints of the trial are overall survival (OS) and progression-free survival (PFS) by blinded independent central review (BICR) in patients with tumor cell PD-L1 expression ≥1% for both Opdivo-based combinations versus chemotherapy. Secondary endpoints of the trial include OS and PFS by BICR in the all-randomized population.

In the Opdivo with chemotherapy arm, patients received treatment with Opdivo 240 mg on Day 1 and Day 15, fluorouracil 800 mg/m²/day on Day 1 through Day 5 (for 5 days), and cisplatin 80 mg/m² on Day 1 of four-week cycle.

Patients received Opdivo for up to 24 months or until disease progression, unacceptable toxicity or withdrawal of consent, and chemotherapy until disease progression, unacceptable toxicity or withdrawal of consent.

In the Opdivo plus Yervoy arm, patients received treatment with Opdivo 3 mg/kg every 2 weeks and Yervoy 1 mg/kg every 6 weeks up to 24 months or until disease progression, unacceptable toxicity or withdrawal of consent.

About Esophageal Cancer

Esophageal cancer is the seventh most common cancer and the sixth leading cause of death from cancer worldwide, with approximately 600,000 new cases and over 540,000 deaths in 2020.

The two most common types of esophageal cancer are squamous cell carcinoma and adenocarcinoma, which account for approximately 85% and 15% of all esophageal cancers, respectively, though esophageal tumor histology can vary by region and country.

Squamous cell carcinoma accounts for approximately 60% of esophageal cancer cases in Europe.

Bristol Myers Squibb: Creating a Better Future for People with Cancer

Bristol Myers Squibb is inspired by a single vision — transforming people’s lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility.

Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine, and through innovative digital platforms, are turning data into insights that sharpen their focus.

Deep scientific expertise, cutting-edge capabilities and discovery platforms enable the company to look at cancer from every angle.

Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. Because as a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.

About Opdivo

Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response.

By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.

Opdivo’s leading global development program is based on Bristol Myers Squibb’s scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has treated more than 35,000 patients.

The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.

In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. 

Opdivo is currently approved in more than 65 countries, including the United States, the European Union, Japan and China.

In October 2015, the Company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.

INDICATIONS

OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of adult patients with unresectable or metastatic melanoma.

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adult patients with unresectable or metastatic melanoma.

OPDIVO® (nivolumab) is indicated for the adjuvant treatment of adult patients with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection.

OPDIVO® (nivolumab), in combination with platinum-doublet chemotherapy, is indicated as neoadjuvant treatment of adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer (NSCLC).

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab) and 2 cycles of platinum-doublet chemotherapy, is indicated for the first-line treatment of adult patients with metastatic or recurrent non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

OPDIVO® (nivolumab) is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma (MPM).

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with intermediate or poor risk advanced renal cell carcinoma (RCC).

OPDIVO® (nivolumab), in combination with cabozantinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).

OPDIVO® (nivolumab) is indicated for the treatment of adult patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.

OPDIVO® (nivolumab) is indicated for the treatment of adult patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT.

This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO® (nivolumab) is indicated for the treatment of adult patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy.

OPDIVO® (nivolumab) is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

OPDIVO® (nivolumab), as a single agent, is indicated for the adjuvant treatment of adult patients with urothelial carcinoma (UC) who are at high risk of recurrence after undergoing radical resection of UC.

OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric (12 years and older) patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.

This indication is approved under accelerated approval based on overall response rate and duration of response.

Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adults and pediatric patients 12 years and older with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.

This indication is approved under accelerated approval based on overall response rate and duration of response.

Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adult patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

OPDIVO® (nivolumab) is indicated for the treatment of adult patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy.

OPDIVO® (nivolumab) is indicated for the adjuvant treatment of completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease in adult patients who have received neoadjuvant chemoradiotherapy (CRT).

OPDIVO® (nivolumab), in combination with fluoropyrimidine- and platinum- containing chemotherapy, is indicated for the treatment of adult patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma.

IMPORTANT SAFETY INFORMATION

Severe and Fatal Immune-Mediated Adverse Reactions

Immune-mediated adverse reactions listed herein may not include all possible severe and fatal immune-mediated adverse reactions.

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue.

While immune-mediated adverse reactions usually manifest during treatment, they can also occur after discontinuation of OPDIVO or YERVOY.

Early identification and management are essential to ensure safe use of OPDIVO and YERVOY. Monitor for signs and symptoms that may be clinical manifestations of underlying immune-mediated adverse reactions.

Evaluate clinical chemistries including liver enzymes, creatinine, adrenocorticotropic hormone (ACTH) level, and thyroid function at baseline and periodically during treatment with OPDIVO and before each dose of YERVOY.

In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information).

In general, if OPDIVO or YERVOY interruption or discontinuation is required, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less.

Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month.

Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy.

Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies and dermatologic reactions) are discussed below.

Immune-Mediated Pneumonitis

OPDIVO and YERVOY can cause immune-mediated pneumonitis.

The incidence of pneumonitis is higher in patients who have received prior thoracic radiation.

In patients receiving OPDIVO monotherapy, immune- mediated pneumonitis occurred in 3.1% (61/1994) of patients, including Grade 4 (<0.1%), Grade 3 (0.9%), and Grade 2 (2.1%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated pneumonitis occurred in 7% (31/456) of patients, including Grade 4 (0.2%), Grade 3 (2.0%), and Grade 2 (4.4%).

In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated pneumonitis occurred in 3.9% (26/666) of patients, including Grade 3 (1.4%) and Grade 2 (2.6%). In NSCLC patients receiving OPDIVO 3 mg/kg every 2 weeks with YERVOY 1 mg/kg every 6 weeks, immune-mediated pneumonitis occurred in 9% (50/576) of patients, including Grade 4 (0.5%), Grade 3 (3.5%), and Grade 2 (4.0%). Four patients (0.7%) died due to pneumonitis.

In Checkmate 205 and 039, pneumonitis, including interstitial lung disease, occurred in 6.0% (16/266) of patients receiving OPDIVO. Immune-mediated pneumonitis occurred in 4.9% (13/266) of patients receiving OPDIVO, including Grade 3 (n=1) and Grade 2 (n=12).

Immune-Mediated Colitis

OPDIVO and YERVOY can cause immune-mediated colitis, which may be fatal. A common symptom included in the definition of colitis was diarrhea.

Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis.

In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. In patients receiving OPDIVO monotherapy, immune-mediated colitis occurred in 2.9% (58/1994) of patients, including Grade 3 (1.7%) and Grade 2 (1%).

In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated colitis occurred in 25% (115/456) of patients, including Grade 4 (0.4%), Grade 3 (14%) and Grade 2 (8%).

In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated colitis occurred in 9% (60/666) of patients, including Grade 3 (4.4%) and Grade 2 (3.7%).

Immune-Mediated Hepatitis and Hepatotoxicity

OPDIVO and YERVOY can cause immune-mediated hepatitis. In patients receiving OPDIVO monotherapy, immune-mediated hepatitis occurred in 1.8% (35/1994) of patients, including Grade 4 (0.2%), Grade 3 (1.3%), and Grade 2 (0.4%).

In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune- mediated hepatitis occurred in 15% (70/456) of patients, including Grade 4 (2.4%), Grade 3 (11%), and Grade 2 (1.8%).

In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated hepatitis occurred in 7% (48/666) of patients, including Grade 4 (1.2%), Grade 3 (4.9%), and Grade 2 (0.4%).

OPDIVO in combination with cabozantinib can cause hepatic toxicity with higher frequencies of Grade 3 and 4 ALT and AST elevations compared to OPDIVO alone. Consider more frequent monitoring of liver enzymes as compared to when the drugs are administered as single agents.

In patients receiving OPDIVO and cabozantinib, Grades 3 and 4 increased ALT or AST were seen in 11% of patients.

Immune-Mediated Endocrinopathies

OPDIVO and YERVOY can cause primary or secondary adrenal insufficiency, immune-mediated hypophysitis, immune-mediated thyroid disorders, and Type 1 diabetes mellitus, which can present with diabetic ketoacidosis.

Withhold OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information). For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated.

Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism; initiate hormone replacement as clinically indicated. Thyroiditis can present with or without endocrinopathy.

Hypothyroidism can follow hyperthyroidism; initiate hormone replacement or medical management as clinically indicated. Monitor patients for hyperglycemia or other signs and symptoms of diabetes; initiate treatment with insulin as clinically indicated.

In patients receiving OPDIVO monotherapy, hypophysitis occurred in 0.6% (12/1994) of patients, including Grade 3 (0.2%) and Grade 2 (0.3%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, hypophysitis occurred in 9% (42/456), including Grade 3 (2.4%) and Grade 2 (6%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, hypophysitis occurred in 4.4% (29/666) of patients, including Grade 4 (0.3%), Grade 3 (2.4%), and Grade 2 (0.9%).

In patients receiving OPDIVO monotherapy, thyroiditis occurred in 0.6% (12/1994) of patients, including Grade 2 (0.2%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, thyroiditis occurred in 2.7% (22/666) of patients, including Grade 3 (4.5%) and Grade 2 (2.2%).

In patients receiving OPDIVO monotherapy, hyperthyroidism occurred in 2.7% (54/1994) of patients, including Grade 3 (<0.1%) and Grade 2 (1.2%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, hyperthyroidism occurred in 9% (42/456) of patients, including Grade 3 (0.9%) and Grade 2 (4.2%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, hyperthyroidism occurred in 12% (80/666) of patients, including Grade 3 (0.6%) and Grade 2 (4.5%).

In patients receiving OPDIVO monotherapy, hypothyroidism occurred in 8% (163/1994) of patients, including Grade 3 (0.2%) and Grade 2 (4.8%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, hypothyroidism occurred in 20% (91/456) of patients, including Grade 3 (0.4%) and Grade 2 (11%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, hypothyroidism occurred in 18% (122/666) of patients, including Grade 3 (0.6%) and Grade 2 (11%).

In patients receiving OPDIVO monotherapy, diabetes occurred in 0.9% (17/1994) of patients, including Grade 3 (0.4%) and Grade 2 (0.3%), and 2 cases of diabetic ketoacidosis. In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, diabetes occurred in 2.7% (15/666) of patients, including Grade 4 (0.6%), Grade 3 (0.3%), and Grade 2 (0.9%).

Immune-Mediated Nephritis with Renal Dysfunction

OPDIVO and YERVOY can cause immune-mediated nephritis. In patients receiving OPDIVO monotherapy, immune-mediated nephritis and renal dysfunction occurred in 1.2% (23/1994) of patients, including Grade 4 (<0.1%), Grade 3 (0.5%), and Grade 2 (0.6%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated nephritis with renal dysfunction occurred in 4.1% (27/666) of patients, including Grade 4 (0.6%), Grade 3 (1.1%), and Grade 2 (2.2%).

Immune-Mediated Dermatologic Adverse Reactions

OPDIVO can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS) has occurred with PD-1/PD-L1 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate nonexfoliative rashes.

YERVOY can cause immune-mediated rash or dermatitis, including bullous and exfoliative dermatitis, SJS, TEN, and DRESS. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non- bullous/exfoliative rashes.

Withhold or permanently discontinue OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information).

In patients receiving OPDIVO monotherapy, immune-mediated rash occurred in 9% (171/1994) of patients, including Grade 3 (1.1%) and Grade 2 (2.2%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated rash occurred in 28% (127/456) of patients, including Grade 3 (4.8%) and Grade 2 (10%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated rash occurred in 16% (108/666) of patients, including Grade 3 (3.5%) and Grade 2 (4.2%).

Other Immune-Mediated Adverse Reactions

The following clinically significant immune-mediated adverse reactions occurred at an incidence of <1% (unless otherwise noted) in patients who received OPDIVO monotherapy or OPDIVO in combination with YERVOY or were reported with the use of other PD-1/PD-L1 blocking antibodies. Severe or fatal cases have been reported for some of these adverse reactions: cardiac/vascular: myocarditis, pericarditis, vasculitis; nervous system: meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy; ocular: uveitis, iritis, and other ocular inflammatory toxicities can occur; gastrointestinal: pancreatitis to include increases in serum amylase and lipase levels, gastritis, duodenitis; musculoskeletal and connective tissue: myositis/polymyositis, rhabdomyolysis, and associated sequelae including renal failure, arthritis, polymyalgia rheumatica; endocrine: hypoparathyroidism; other (hematologic/immune): hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis (HLH), systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection.

In addition to the immune-mediated adverse reactions listed above, across clinical trials of YERVOY monotherapy or in combination with OPDIVO, the following clinically significant immune-mediated adverse reactions, some with fatal outcome, occurred in <1% of patients unless otherwise specified: nervous system: autoimmune neuropathy (2%), myasthenic syndrome/myasthenia gravis, motor dysfunction; cardiovascular: angiopathy, temporal arteritis; ocular: blepharitis, episcleritis, orbital myositis, scleritis; gastrointestinal: pancreatitis (1.3%); other (hematologic/immune): conjunctivitis, cytopenias (2.5%), eosinophilia (2.1%), erythema multiforme, hypersensitivity vasculitis, neurosensory hypoacusis, psoriasis.

Some ocular IMAR cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada–like syndrome, which has been observed in patients receiving OPDIVO and YERVOY, as this may require treatment with systemic corticosteroids to reduce the risk of permanent vision loss.

Infusion-Related Reactions

OPDIVO and YERVOY can cause severe infusion-related reactions. Discontinue OPDIVO and YERVOY in patients with severe (Grade 3) or life-threatening (Grade 4) infusion-related reactions. Interrupt or slow the rate of infusion in patients with mild (Grade 1) or moderate (Grade 2) infusion-related reactions. In patients receiving OPDIVO monotherapy as a 60-minute infusion, infusion-related reactions occurred in 6.4% (127/1994) of patients. In a separate trial in which patients received OPDIVO monotherapy as a 60-minute infusion or a 30- minute infusion, infusion-related reactions occurred in 2.2% (8/368) and 2.7% (10/369) of patients, respectively. Additionally, 0.5% (2/368) and 1.4% (5/369) of patients, respectively, experienced adverse reactions within 48 hours of infusion that led to dose delay, permanent discontinuation or withholding of OPDIVO. In melanoma patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, infusion-related reactions occurred in 2.5% (10/407) of patients. In HCC patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, infusion-related reactions occurred in 8% (4/49) of patients. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, infusion-related reactions occurred in 5.1% (28/547) of patients. In MSI- H/dMMR mCRC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, infusion-related reactions occurred in 4.2% (5/119) of patients. In MPM patients receiving OPDIVO 3 mg/kg every 2 weeks with YERVOY 1 mg/kg every 6 weeks, infusion-related reactions occurred in 12% (37/300) of patients.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation

Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with OPDIVO or YERVOY.

Transplant-related complications include hyperacute graft-versus-host-disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause).

These complications may occur despite intervening therapy between OPDIVO or YERVOY and allogeneic HSCT.

Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with OPDIVO and YERVOY prior to or after an allogeneic HSCT.

Embryo-Fetal Toxicity

Based on its mechanism of action and findings from animal studies, OPDIVO and YERVOY can cause fetal harm when administered to a pregnant woman. The effects of YERVOY are likely to be greater during the second and third trimesters of pregnancy. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with OPDIVO and YERVOY and for at least 5 months after the last dose.

Increased Mortality in Patients with Multiple Myeloma when OPDIVO is Added to a Thalidomide Analogue and Dexamethasone.

https://news.bms.com/news/corporate-financial/2022/Bristol-Myers-Squibb-Receives-European-Commission-Approval-for-Opdivo-nivolumab-with-Chemotherapy-as-First-Line-Treatment-for-Patients-with/default.aspx

XARENO study revealed Xarelto™ was associated with net clinical benefit and a reduced risk of kidney failure

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XARENO study revealed Xarelto™ was associated with net clinical benefit and a reduced risk of kidney failure

 April 4, 2022: “In the XARENO study, after a minimum follow up period of one year, Xarelto (rivaroxaban) was associated with a greater net clinical benefit (lower event rates for stroke and other thromboembolic events, major bleeding and all-cause mortality) and a reduced risk of kidney failure in patients with non-valvular atrial fibrillation (NVAF) and advanced chronic kidney disease (CKD) compared to vitamin K antagonists.

The study findings were presented at the American Congress of Cardiology’s 71st Annual Scientific Session (ACC.22).

“Chronic kidney disease is a common and potentially deadly condition that is widely underrecognized, despite the fact it can severely impact patients’ quality of life,” said Reinhold Kreutz, Professor of Clinical Pharmacology, Charité University – Medicine Berlin.

“The XARENO study findings provide important evidence that can help physicians in the management of patients with atrial fibrillation and chronic kidney disease and help reduce patients’ risk of progressing to kidney failure.”

XARENO is the first prospective observational study to evaluate the effectiveness and safety of Xarelto versus VKAs or no oral anticoagulation (at the discretion of attending physicians) in treating patients with NVAF and advanced CKD.

The prevention of worsening renal function is an important additional therapeutic target beyond stroke prevention when it comes to the selection of an oral anticoagulant in patients with atrial fibrillation (AF).

The XARENO study was undertaken to investigate the real-world effectiveness and safety of Xarelto compared with VKAs in this vulnerable patient group with AF and advanced CKD.

The study adds to the evidence obtained in the randomized controlled ROCKET-AF study and supports the use of Xarelto in this patient group including patients with CKD stage 4.

In agreement with previous data demonstrating various benefits of rivaroxaban over VKAs on kidney outcomes, XARENO also suggests a potential reduction in kidney failure of Xarelto vs VKA.

With XARENO and previous studies like ANTENNA Xarelto provides the broadest evidence on preservation of renal function compared to all other NOACs.

“Previous trials evaluating stroke prevention in atrial fibrillation have excluded patients with advanced chronic kidney disease. Consequently, the clinical impact of NOACs versus VKAs in this patient population was unknown,” said Dr. Mike Devoy, Chief Medical Officer and Head of Medical Affairs and Pharmacovigilance for the Pharmaceuticals Division at Bayer. “The XARENO study provides crucial new insights into how we can help to prevent disease progression and improve clinical outcomes in people with atrial fibrillation and chronic kidney disease.”

About atrial fibrillation (AF) and chronic kidney disease (CKD)

AF is the most common sustained cardiac rhythm disorder. In AF, the upper chambers of the heart (atria) contract irregularly.

As a result, blood does not flow properly, potentially allowing blood clots to form. These blood clots can break loose and travel to the brain, resulting in a stroke.

Patients with AF can have a up to 5 times higher risk of stroke than those without AF. AF is frequently associated with comorbidities, including CKD.

It’s estimated that 15–20% of people with AF also have CKD. CKD is a common and potentially deadly condition that is widely underrecognized.

The disease progresses silently and unpredictably, with many symptoms not appearing until CKD is well-advanced. CKD is one of the most frequent complications arising from diabetes and is also an independent risk factor of cardiovascular disease.

Previous studies have found that patients with both AF and renal impairment are at higher risk for bleeding and stroke. They are also more likely to be undertreated with oral anticoagulation such as warfarin than those with normal renal function.

About XARENO

The XA inhibition in RENal patients with non-valvular atrial fibrillation Observational registry (XARENO) was a prospective, non-interventional, international multicenter study recruiting AF patients with CKD in five European countries.

The results build on findings from a retrospective database analysis which indicated that Xarelto may be associated with lower risks of adverse renal outcomes in patients with CKD and NVAF, compared with VKA.

Between April 2016 and January 2020, 1,550 patients were enrolled in the study. Patients treated with Xarelto or VKA having estimated glomerular filtration rates (eGFR) between 15 and 49 mL/min per 1.73 m2 were eligible for inclusion.

Patients without anticoagulation at the discretion of the attending physicians were also enrolled for explorative analysis.

The study population comprised 766 patients in the Xarelto group, 695 in the VKA group, and 89 in the group without anticoagulation and 85 patients not eligible/with missing information.

Patients were treated with either Xarelto or VKA at the discretion of the attending physicians. Pre-specified follow-up was at least 12 months with a planned extended data collection period for one up to two additional years.

Primary outcomes, as determined by blinded adjudication, included progression of CKD and net-clinical benefit (stroke and other thromboembolic events, major bleeding, and all-cause mortality).

Propensity score matched analysis (PSMA) was used to compare the Xarelto and VKA groups.

After one year follow up, the study found that in PSMA, baseline eGFR was similar in both groups and numerically higher in the rivaroxaban group after follow-up (difference 1.0 mL/min per 1.73 m2, 95% confidence interval [CI] -0.48 to 2.51, p=0.18).

The frequency of net-clinical benefit events was 12.9% (51/397) in the rivaroxaban and 18.3% (75/410) in the VKA group (incidence rate ratio [IRR] 0.68, 95% CI 0.47 to 0.96, p=0.03).

The incidence risk ratio (IRR) for progression to CKD stage 5 was 0.40 (CI 0.22 to 0.71) and the IRR for in the initiation of chronic renal replacement therapy was 0.08 (CI 0.01 to 0.63).

About Rivaroxaban (Xarelto™)
Rivaroxaban is the most broadly indicated non-vitamin K antagonist oral anticoagulant (NOAC) worldwide and is marketed under the brand name Xarelto. Xarelto is approved for more venous and arterial thromboembolic (VAT) conditions than any other NOAC:

· The prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation (AF) with one or more risk factors
· The treatment of pulmonary embolism (PE) in adults
· The treatment of deep vein thrombosis (DVT) in adults
· The prevention of recurrent PE and/or DVT in adults
· The prevention of venous thromboembolism (VTE) in adult patients undergoing elective hip replacement surgery
· The prevention of VTE in adult patients undergoing elective knee replacement surgery
· The prevention of atherothrombotic events after an Acute Coronary Syndrome in adult patients with elevated cardiac biomarkers when co-administered with acetylsalicylic acid (ASA) alone or with ASA plus clopidogrel or ticlopidine
· The prevention of atherothrombotic events in adult patients with coronary artery disease (CAD) or symptomatic peripheral artery disease (PAD) at high risk for ischemic events when co-administered with acetylsalicylic acid (ASA)
· Treatment of venous thromboembolism (VTE) and prevention of VTE recurrence in children and adolescents aged less than 18 years after at least 5 days of initial parenteral anticoagulation treatment
· Thromboprophylaxis (prevention of VTE and VTE related events) in children aged two years and older with congenital heart disease who have undergone the Fontan procedure

Xarelto is approved in more than 130 countries, although the approved labelling, including the number of indications may differ from country to country. Since launch in 2008, more than 100 million patients have been treated.

Rivaroxaban was discovered by Bayer and is being jointly developed with Janssen Research & Development, LLC. Xarelto is marketed outside the U.S. by Bayer and in the U.S. by Janssen Pharmaceuticals, Inc. (Janssen Research & Development, LLC and Janssen Pharmaceuticals, Inc. are part of the Janssen Pharmaceutical Companies of Johnson & Johnson).

Anticoagulant medicines are therapies used to prevent or treat serious illnesses and potentially life-threatening conditions.

Before initiating treatment with anticoagulant medicines, physicians should carefully assess the benefit and risk for the individual patient.

Responsible use of Xarelto is a very high priority for Bayer, and the company has developed a Prescribers Guide for physicians and a Xarelto Patient Card for patients to support best practice.”

https://media.bayer.com/baynews/baynews.nsf/id/XARENO-study-revealed-XareltoTM-associated-clinical-benefit-a-reduced-kidney-failure-compared?Open&parent=news-overview-category-search-en&ccm=020

AZ’s Self-administered SC monthly dose with a potential best-in-class efficacy profile

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AZ’s Self-administered SC monthly dose with a potential best-in-class efficacy profile

April 04, 2022: “Positive results from the ETESIAN Phase IIb trial showed AZD8233 (an investigational antisense oligonucleotide [ASO], also known as ION449) met the primary endpoint at 50 mg with 73% (95% confidence interval [CI]: -77%, -68%) reduction in low-density lipoprotein cholesterol (LDL-C) levels, from baseline.

The trial also met the secondary endpoints, including significantly reducing proprotein convertase subtilisin/kexin type 9 (PCSK9) levels by 89% (95% CI: -91%, -86%), with sustained reductions maintained over the dosing intervals, and through to week 14 (6 weeks after last dose) at 50 mg dose.

Reduction of PCSK9 levels leads to increases in LDL receptor levels, which results in lower LDL-C levels in the bloodstream and reduces the risk of developing coronary heart disease.

AZD8233 was generally well-tolerated during the treatment duration.

Three dose levels of AZD8233 were evaluated (15mg, 50mg, 90mg), given monthly by subcutaneous injection over the 12 week dosing period.

All active arms demonstrated reductions in LDL-C and PCSK9 levels at week 12 compared to placebo.

The trial was conducted in patients with high-risk hypercholesterolemia on a high-dose statin.

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: “Today, we are pleased to announce that ETESIAN Phase IIb for AZD8233 demonstrated a clear dose-response for both PCSK9 and LDL-C levels.

The results underscore AZD8233’s potential best-in-class efficacy profile, and supports its further development as a next generation PCSK9 inhibitor that is easily self-administered monthly.”

Brett Monia, CEO, Ionis Pharmaceuticals said: “The positive results of the ETESIAN study, along with the clinical studies to date, reinforces our confidence that ION449 (AZD8233) is a potential new treatment option that may be able to change the current standard of care for patients affected by hypercholesterolemia who have cardiovascular disease.”

More than half of patients with cardiovascular disease at high-risk of a major secondary event do not meet their LDL-C goals, despite taking a high-intensity statin.1-3 Elevated LDL-C is a key risk factor for cardiovascular disease, resulting in approximately 2.6 million deaths worldwide every year.4

AZD8233 is a next generation PCSK9 inhibitor with a unique mode of action and is the only PCSK9 ASO, which acts upstream of current PCSK9 inhibitors, targeting gene expression in the nucleus. It is designed to reduce blood cholesterol levels in patients with hypercholesterolemia by targeting PCSK9, an important regulator of LDL-C.

Results from the ETESIAN Phase IIb trial were presented on 4 April 2022 at the American College of Cardiology’s 71st Annual Scientific Session.

Results from the SOLANO Phase IIb trial assessing the safety, efficacy and tolerability of AZD8233 in patients with hypercholesterolemia is anticipated later in 2022.

Notes

Hypercholesterolemia
Hypercholesterolemia, or elevated LDL-C levels in the blood, is an important risk factor for cardiovascular disease, the leading cause of death worldwide.

There is a significant unmet medical need for stronger LDL-C lowering therapies in secondary prevention patients with approximately 50% who are not meeting their treatment goals despite taking a high-intensity statin.

One in six patients with LDL-C >100mg/dL will suffer a second major adverse cardiovascular event over approximately three years.

AZD8233
AZD8233 (also known as ION 449), dosed once monthly via subcutaneous administration, is a novel, investigational ASO therapy designed to reduce blood cholesterol levels in patients with hypercholesterolemia by inhibiting PCSK9 expression in the nucleus.

By reducing PCSK9 levels, AZD8233 is expected to increase the number of LDL receptors available to clear LDL from the blood, thereby lowering LDL-C levels.

ETESIAN
ETESIAN was a randomised, parallel-group, double-blind, placebo-controlled, dose-ranging Phase IIb study of AZD8233 in patients with hypercholesterolemia on a background of high-dose statin.

The primary endpoint was to assess the efficacy of AZD8233 across different dose levels versus placebo in reducing serum LDL-C levels.

Secondary endpoints included change in PCSK9 levels and the assessment of safety and tolerability of AZD8233.

The reduction from baseline to week 12 in LDL-C at the 15 mg and 90 mg monthly dose was 39% (95% CI: -48%, -29%) and 79% (95% CI: -83%, -76%), respectively.

The reduction from baseline to week 12 in PCSK9 levels at the 15 mg and 90 mg monthly dose was 58% (95% CI: -66, -48) and -94% (95% CI: -95, -92) respectively.

In the AZD8233 90 mg group, transient, moderate treatment-emergent elevations in liver enzyme levels occurred in some patients.

AstraZeneca in CVRM
Cardiovascular, Renal and Metabolism (CVRM), part of BioPharmaceuticals, forms one of AstraZeneca’s three disease areas and is a key growth driver for the Company.

By following the science to understand more clearly the underlying links between the heart, kidneys and pancreas, AstraZeneca is investing in a portfolio of medicines for organ protection and improving outcomes by slowing disease progression, reducing risks and tackling co-morbidities.

The Company’s ambition is to modify or halt the natural course of CVRM diseases and potentially regenerate organs and restore function, by continuing to deliver transformative science that improves treatment practices and CV health for millions of patients worldwide.”

https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2022/azd8233-reduced-low-density-lipoprotein-cholesterol-levels-73-patients-high-risk-hypercholesterolemia-etesian-phase-iib-trial.html

Sanofi launches first-in-pharma Diversity, Equity & Inclusion Board

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Sanofi launches first-in-pharma Diversity, Equity & Inclusion Board

April 4, 2022: “Sanofi launches its Diversity, Equity & Inclusion (DE&I) Board, the first-of-its-kind in the pharmaceutical industry to feature outside advisors.

Sanofi’s DE&I Board will include three of the most influential voices in the DE&I space as Board members appointed for 3 years: organizational psychologist & best-selling author John Amaechi, award-winning social entrepreneur Caroline Casey, and DE&I pioneer and renowned thought-leader Dr. Rohini Anand.

Sanofi’s DE&I strategy was revamped in June 2021 with set objectives toward 2025, built around three key pillars: building representative leadership, creating a work environment where employees can bring their whole selves and engaging with the company’s diverse communities.

The DE&I Board’s role is to ensure Sanofi’s DE&I strategy is rightly executed, to monitor progress on the company’s 2025 targets and to advise on how to accelerate the company’s impact in this space.

Together with the DE&I Board, Sanofi is launching a global Employee Resource Group (ERG) framework and five global focused ERGs: Gender+, Generations+, Pride+, Ability+ and Culture and Origins+, which will allow already existing local ERGs to scale and grow. ERGs are voluntary, employee-led groups that help create a diverse and inclusive workplace.

Critical in supporting their members’ professional and personal growth and in cultivating a sense of belonging, they ensure the company reflects, values and listens to its diverse employees’ communities.

Paul Hudson
CEO of Sanofi
“We’re committed to driving diversity, equity and inclusion in Sanofi and beyond. These new initiatives will help us bring the outside in, so we can hear, listen and learn faster, and grow stronger as we continue our DE&I journey.”

The DE&I Board is composed of eleven members, including seven members from Sanofi’s leadership – Paul Hudson, Chief Executive Officer, Natalie Bickford, Chief People Officer, Olivier Charmeil, Head of General Medicines, Roy Papatheodorou, General Counsel & Head of Legal, Ethics & Business Integrity, John Reed, Head of Research & Development, Thomas Triomphe, Head of Vaccines, and Raj Verma, Chief Diversity, Culture & Experience Officer.

Raj Verma will chair the DE&I Board. One member will be one of the company’s five global Employee Resource Group Leads, with rotation among all global ERG Leads on an annual basis.

The DE&I Board will meet 3 times per year and progress on the 2025 targets will continue to be communicated on a quarterly basis.

John Amaechi
“I am always excited to support organizations looking to ensure that whether for colleagues, stakeholders or consumers – they stand for fairness, equity and the preservation of human dignity. 

I am a scientist first and bring an understanding of what can work to performance through improving inclusion and equity in the context of a large, complex multinational company with a strong history and tradition. It’s clear there are many strong advocates within the company, and I am delighted to add my insights and expertise to those already present within Sanofi.”

Dr. Rohini Anand
“I am thrilled to join Sanofi’s DE&I Board as it affords me an opportunity to influence the critical need to address health care disparities globally.

With my experience in leading global DE&I transformations I am motivated to support Sanofi as it seeks to foster an equitable and inclusive culture that enables breakthrough innovations because it is the desired destination for diverse talent. 

I am impressed by the authenticity and humility with which the leadership approaches DE&I and its willingness and openness to learn from external thought leaders.”

Caroline Casey
“It’s a real honour to be joining the Sanofi DE&I Board which will support the strategic evolution of Business Inclusion focusing on the complex intersectional nature of diversity, equity, and inclusion.

As a supporter of removing the decisive siloed approach which has and continues to create exclusion and mistrust, I am proud to bring the voice of disability business inclusion front and centre of Sanofi’s strategy both as a person with lived experience and as the founder of The Valuable 500.”

Sanofi’s DE&I Board external members

John Amaechi is an organizational psychologist, best-selling author, Chartered Scientist (CSci), elected Fellow of the Royal Society for Public Health, Research Fellow at the University of East London, and Founder of APS Intelligence.

A former NBA sportsman, John Amaechi serves as a mentor to many, a teacher to some, and always uses his deep psychological insight combined with real life experience to provide a touchstone for people and companies who want to thrive, achieve and align their beliefs, values and ethics.

Dr. Rohini Anand, is a strategic business leader, Board member and author. With expertise that spans executive leadership, human capital, global corporate responsibility, wellness and diversity equity and inclusion, Rohini brings a unique perspective on the critical alignment of the business culture and the triple bottom line (People, Planet, Profit) to drive exceptional performance.

Most recently Rohini was Senior Vice-President Corporate Responsibility and Global Chief Diversity Officer for Sodexo.

Caroline Casey is a businesswoman and activist, founder of The Valuable 500, the world’s largest CEO collective and business move for disability inclusion.

Recently appointed President of the International Agency for the Prevention of Blindness (IAPB), Caroline also sits on several Diversity and Inclusion Boards to include L’Oréal and Sky.”

https://www.sanofi.com/en/media-room/press-releases/2022/2022-04-04-12-00-00-2415480

ViiV Healthcare announces FDA approval of Triumeq PD for HIV

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ViiV Healthcare announces FDA approval of Triumeq PD for HIV

 March 30, 2022: “ViiV Healthcare, the global specialist HIV company majority-owned by GlaxoSmithKline plc, with Pfizer Inc. and Shionogi B.V. as shareholders, has announced that the U.S. Food and Drug Administration has approved a NDA for a dispersible tablet formulation of the fixed dose combination of abacavir, dolutegravir and lamivudine for the treatment of pediatric patients weighing 10kgs to <25 kgs with human immunodeficiency virus type 1 (HIV-1).

In addition, a supplemental new drug application (sNDA) has been approved for Triumeq tablet, lowering the minimum weight that a child with human immunodeficiency virus type 1 (HIV-1) can be prescribed this medicine to 25kgs from 40kgs.

According to UNAIDS, approximately 1.7 million children globally were living with HIV in 2020, with most AIDS-related deaths among this population occurring during the first five years of life.

Therefore, the availability of age-appropriate treatment options is critical in ensuring young children can access optimal care.

Deborah Waterhouse, CEO of ViiV Healthcare, said: “We are delighted with today’s FDA approval because it gives children living with HIV another age-appropriate treatment option.

Developing paediatric formulations of anti-retroviral treatments is a priority for ViiV Healthcare because we want to ensure that no one living with HIV is left behind and this approval means that we are one step closer to closing the gap between HIV treatment options available for adults and children.”

Today’s FDA approval is an important step in fulfilling ViiV Healthcare’s commitment to bring optimised paediatric formulations containing dolutegravir to children.

In addition to today’s regulatory milestones, an application to approve the new dispersible tablet of the fixed dose combination of abacavir, dolutegravir and lamivudine for the treatment of paediatric patients with human immunodeficiency virus type 1 (HIV-1) and to extend the current approved Marketing Authorisation of Triumeq tablets to include a paediatric indication for children is currently under review by the European Medicines Agency (EMA).

Chip Lyons, President and CEO of the Elizabeth Glaser Paediatric AIDS Foundation (EGPAF), said: “Children are still disproportionality impacted by the HIV epidemic with only half of the 1.7 million children living with HIV accessing the lifesaving treatment they need and even fewer still reaching viral suppression.

An obvious barrier to treatment is that for young children, tablets can be hard to swallow or unpleasant in taste and this presents a real challenge to many caregivers’ ability to administer life-saving medicine.

Today’s approval of a child-friendly formulation of a single tablet regimen will help meet the urgent needs of this vulnerable population.”

Through its paediatric voluntary licences, ViiV Healthcare enables generic versions of dolutegravir to be manufactured and sold royalty-free for the treatment of children living with HIV in all least-developed, low-income, lower-middle-income and sub-Saharan Africa countries, as well as some upper-middle-income countries.

In order to ensure licensees expedite the development and introduction of optimised paediatric formulations containing dolutegravir to help the children most affected by HIV, the majority of whom reside in sub-Saharan Africa, ViiV Healthcare works with the Clinton Health Access Initiative (CHAI) and Unitaid in a public-private partnership.

About Triumeq

Two essential steps in the HIV life cycle are replication – when the virus turns its RNA copy into DNA – and integration – the moment when viral DNA becomes part of the host cell’s DNA.

These processes require two enzymes called reverse transcriptase and integrase. NRTIs and integrase inhibitors interfere with the action of the two enzymes to prevent the virus from replicating and further infecting cells.

Trademarks are owned by or licensed to the ViiV Healthcare group of companies.

Important Safety Information (ISI) for TRIUMEQ and TRIUMEQ PD (abacavir, dolutegravir, and lamivudine) tablets“

https://www.gsk.com/en-gb/media/press-releases/viiv-healthcare-announces-us-fda-approval-of-triumeq-pd-the-first-dispersible-single-tablet-regimen-containing-dolutegravir-a-once-daily-treatment-for-children-living-with-hiv/

Bayer set to drive breakthrough innovations in the Life Sciences

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Bayer set to drive breakthrough innovations in the Life Sciences

April 1, 2022: “Bayer held its first ever Breakthrough Innovation Forum, focusing on longer-term opportunities for health and agriculture leveraging emerging technologies.

The event followed Bayer’s recent short- and mid-term pipeline updates for its Pharma and Crop Science Divisions and shared further insights on Bayer’s ongoing progress to drive long-term breakthrough innovations in the Life Sciences.

Renowned experts and Bayer executives illustrated how a forthcoming wave of innovations will open new opportunities in next-generation healthcare and in providing farming solutions to make agriculture more sustainable and less resource intensive.

In conjunction with the event, Bayer announced that it is accelerating its investment in its Leaps by Bayer impact investment unit with more than 1.3 billion euros funding until end of 2024.

“We stand at the dawn of a new age of innovation in the Life Sciences,” said Werner Baumann, Chairman of the Board of Management of Bayer AG. “Our ability to tackle some of the greatest challenges is increasing rapidly.

From providing answers for incurable diseases, equipping people with preventive tools to live healthier, better and longer lives, to producing more agricultural output whilst significantly reducing inputs and respecting the planetary boundaries.

This ability is particularly driven by the accelerating confluence of biology, chemistry, advanced computing, data analytics and artificial intelligence.

As a leader in health and nutrition, Bayer is further stepping up its efforts to be a driver of this new era of innovation. Ultimately, better innovation is the engine that drives superior business results and outperformance.”

Tackling humanity’s biggest challenges with Leaps by Bayer

Leaps by Bayer follows a unique approach aimed at tackling ten of humanity’s biggest challenges such as curing cancer or reducing the environmental impact of agriculture.

“Over the past seven years, we have invested more than 1.3 billion euros across a portfolio comprising more than 50 companies – all geared towards shifting core paradigms in the sectors of Health and Agriculture,” said Jürgen Eckhardt, Head of Leaps by Bayer.

“With Bayer stepping up its investment in Leaps over the coming years, we will be able to continue on our successful path and provide funding for the brightest minds working on solutions that truly make a difference for people and the planet.”

Leaps has embarked on numerous joint ventures – such as JoynBio or the former portfolio company BlueRock Therapeutics which is now fully owned by Bayer – and successfully led several investment rounds.

One example is Recursion, an AI-focused company working to find new drug treatments for lung fibrosis and other fibrotic diseases, which successfully went public in April 2021.

The Breakthrough Innovation Forum features CEOs of Leaps’ portfolio companies Cellino, Andes and Ukko to share insights on their missions and technologies in health and agriculture.

Driving breakthrough innovations in health and agriculture

The event also provided tangible examples of Bayer’s ongoing work to change the paradigms in Life Sciences.

In health, the prospects of this new era of innovation are expected to significantly enlarge the toolbox of technologies and enable scientists around the world to address areas of high unmet medical need.

“The convergence of biology, chemistry and data is opening up fundamentally new ways to understand and treat disease. Breakthrough innovation, powered by new technologies, enables us to not only treat symptoms, but to potentially stop or reverse progression of a disease – and offers the promise of treatment options that are truly transformative for patients,” said Stefan Oelrich, Member of the Board of Bayer AG and President of the Pharmaceuticals division.

Bayer is investing strongly in new areas of biomedical innovation, especially in the fields of cell and gene therapies. Over the past three years, Bayer has invested more than 2.5 billion euros to build up a Cell & Gene Therapy Platform, including the acquisitions of BlueRock Therapeutics and Asklepios BioPharmaceutical (AskBio).

In addition, Bayer is driving innovation in strategic collaborations with partners such as Mammoth Biosciences to leverage the collaborative advantages of partnerships.

Already today, the company’s strong preclinical and clinical cell and gene therapy portfolio is benefitting its pipeline, with eight projects in various stages of clinical development.

These cover therapeutic areas with a high unmet medical need, with leading programs in Parkinson’s disease, Pompe disease and congestive heart failure.

Bayer has also significantly strengthened its drug discovery capabilities through its acquisition of Vividion Therapeutics, a biopharmaceutical company utilizing novel discovery technologies to unlock high value, traditionally undruggable targets with precision therapeutics.

Moreover, the company is tapping into the potential of precision health in consumer healthcare.

With its majority ownership of Care/of, a personalized nutrition company originally invested in by Bayer’s Leaps arm, Bayer is positioned to tap into the growth and future potential of the personalized supplements market.

Further, the company has secured innovation partnerships in the field of healthy aging, which use novel biological insights to inform how the right nutrition and lifestyle choices can improve cellular health and promote healthy aging.

These efforts complement the company`s portfolio of science-based nutritional supplements and preventive health products, which have seen double-digit year-over-year growth in each of the past two years.

“The pandemic has heightened the importance of everyday health,” said Heiko Schipper, Member of the Board of Management of Bayer AG and President of the Consumer Health division.

“Advancing innovation-driven solutions in self-care will enable individuals to take more proactive, personalized care of their everyday health.”

In agriculture, Bayer is building on the power of emerging new technologies to create a sustainable and resilient food system and help growers around the world produce more with fewer resources while reducing emissions and removing carbon from the atmosphere.

“Bayer’s R&D investment of 2 billion euros annually in our Crop Science division is unparalleled in the industry, leading to a robust innovation pipeline spanning seeds and trait technologies, crop protection and digital solutions valued at up to 30 billion euros peak sales potential over the next two decades – with approximately half accounting for incremental growth,” said Rodrigo Santos, Member of the Board of Bayer AG and President of the Crop Science division.

On the basis of RNAi technology, Bayer recently launched the first-ever biotech defence against corn rootworm, enabling farmers to control a pest that costs around 1 billion euros annually in crop damage while reducing the need for crop protection.

With its short-stature corn, planned to launch as part of Bayer’s newly introduced Smart Corn System in 2023, Bayer is going to bring a more weather resistant plant to the market.

Short-stature corn is able to withstand extreme conditions emerging from climate change, thus reducing the risk of crop loss and contributing to food security.

Leveraging its unparalleled digital farming platform, Bayer is a leading force in the decarbonization of agriculture.

The Bayer Carbon Initiative incentivizes farmers to embrace the use of climate smart practices such as no-till or cover crops.

In addition, it uses next-generation technology to quantify and track the impact of these practices, underlining Bayer’s pioneering role and its unique position in advancing digital capabilities for the food, feed, fuel, and fiber value chain.”

https://media.bayer.com/baynews/baynews.nsf/id/Bayer-set-to-drive-breakthrough-innovations-in-the-Life-Sciences?Open&parent=news-overview-category-search-en&ccm=020

Novartis announces EU approval of Beovu® for diabetic macular edema

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Novartis announces EU approval of Beovu® for diabetic macular edema

March 31, 2022: “Novartis announced that the European Commission has approved Beovu® (brolucizumab) 6 mg for the treatment of visual impairment due to diabetic macular edema (DME).

Today’s approval in DME represents the second indication for Beovu granted by the EC, which was first approved for the treatment of wet age-related macular degeneration in 2020.

The EC decision applies to all 27 European Union (EU) member states as well as Iceland, Norway and Liechtenstein.

The EC approval was based on year one data from the Phase III, randomized, double-masked KESTREL and KITE* studies, which met their primary endpoint of non-inferiority in change in best-corrected visual acuity (BCVA) from baseline versus aflibercept at year one.

In both trials, following the loading phase, over half of patients (55.1% in KESTREL and 50.3% in KITE) in the Beovu 6 mg arm remained on a 12-week dosing interval through year one.

Aflibercept dosing was aligned to the approved EU label in year one of treatment.

In aggregate, a numerically lower proportion of patient eyes treated with Beovu had intraretinal fluid, subretinal fluid or both at week 52 versus eyes treated with aflibercept (in KESTREL 60.3% in Beovu arm versus 73.3% in aflibercept arm; in KITE 54.2% versus 72.9%, respectively; testing for statistical significance was not performed).

Per the approved prescribing information, following the loading phase of five doses injected six weeks apart, physicians may individualize treatment for DME patients based on their disease activity, as assessed by vision and fluid-related parameters.

In patients without disease activity, physicians should consider 12-week intervals between Beovu treatments; in patients with disease activity, physicians should consider eight-week intervals between treatments.

“This approval marks a significant milestone for DME patients, many of whom are of working age and struggle with adherence due to the need to manage multiple comorbidities related to diabetes,” said Jill Hopkins, SVP and Global Development Unit Head, Ophthalmology, Novartis Pharmaceuticals.

“KESTREL and KITE were the first pivotal trials to assess an anti-VEGF on six-week dosing intervals in the loading phase, suggesting Beovu may offer fewer injections from the start of treatment through year one.*

The EC approval of Beovu in DME may thus help address unmet needs.”

The most common ocular and non-ocular adverse events (≥5%) at year one in KESTREL and KITE were conjunctival hemorrhage, nasopharyngitis and hypertension.

Intraocular inflammation (IOI) rates in KESTREL were 4.7% for brolucizumab 3 mg (including 1.6% retinal vasculitis), 3.7% for Beovu 6 mg (including 0.5% retinal vasculitis), and 0.5% for aflibercept 2 mg.

IOI rates in KITE were equivalent (1.7%) between the Beovu 6 mg and aflibercept 2 mg arms with no retinal vasculitis reported.

Retinal vascular occlusion was reported in KESTREL for brolucizumab 3 mg (1.1%) and 6 mg (0.5%), and in KITE for brolucizumab and aflibercept (0.6% each).

The majority of these events were manageable and resolved with routine clinical care.

In KESTREL, the percentage of patients who experienced ≥15 letter loss from baseline at year one was 1.6% for brolucizumab 3 mg, 0% for Beovu 6 mg and 0.5% for aflibercept.

In KITE, the percentage of patients who experienced ≥15 letter loss from baseline at year one was 1.1% for Beovu 6 mg and 1.7% for aflibercept.

Brolucizumab 6 mg is the commercialized dose of Beovu. 

Novartis remains committed to bringing Beovu to the patients who may benefit from this important medicine.

Regulatory applications for Beovu in DME are under review by the U.S. Food and Drug Administration (FDA) and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA). Discussions with additional health authorities regarding Beovu are ongoing.

*Aflibercept dosing was aligned to the approved EU label in year one of treatment

About the KESTREL and KITE clinical trials
KESTREL and KITE are global, randomized, double-masked, Phase III, two-year studies comparing the safety and efficacy of Beovu and aflibercept in the treatment of patients with visual impairment due to DME.

KESTREL and KITE involved 926 total patients in 36 countries.

In the loading phase of both trials, patients in the Beovu arms were treated every six weeks for a total of five doses; patients in the aflibercept arms were treated every four weeks for a total of five doses, in line with its label.

In the first year of the study, following the loading phase, patients in the Beovu arms were subsequently treated every 12 weeks, with those demonstrating disease activity moved to dosing every eight weeks.

After the loading phase, patients in the aflibercept arms were treated every eight weeks.

About diabetic macular edema (DME)
DME is a common microvascular complication in patients with diabetes that may have a debilitating impact on visual acuity, eventually leading to blindness.

DME is a leading cause of blindness in adults in developed countries, affecting 12% of patients with type 1 diabetes and 28% of those with type 2 diabetes.

Consistently high blood sugar levels associated with diabetes can damage small blood vessels in the eye, causing them to leak fluid.

This damage leads to an excess of vascular endothelial growth factor (VEGF).

VEGF is a protein that stimulates the growth of blood vessels.

At elevated levels in DME, VEGF stimulates the growth of abnormal, leaky blood vessels1,7. The resulting accumulation of fluid (known as edema) in the macula is a key marker of disease activity and can lead to vision loss.

The macula is the area of the retina responsible for sharp, central vision.

Early symptoms of DME include blurry or wavy central vision and distorted color perception, although the disease can also progress without symptoms at early stages

About Beovu (brolucizumab) 6 mg
Beovu (brolucizumab, also known as RTH258) 6 mg is approved for the treatment of wet age-related macular degeneration (AMD) in more than 70 countries, including in the US, EU, UK, Japan, Canada and Australia.

In March 2022, Beovu was also approved by the European Commission (EC) to treat diabetic macular edema (DME), applying to all 27 European Union member states as well as Iceland, Norway and Liechtenstein.

Additional trials, which study the effects of brolucizumab in patients with wet AMD, diabetic macular edema (DME), and proliferative diabetic retinopathy (PDR), are currently ongoing.”

https://www.novartis.com/news/media-releases/novartis-announces-european-commission-approval-beovu-people-living-diabetic-macular-edema

EUROAPI listing on Euronext Paris expected on May 6, 2022

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EUROAPI listing on Euronext Paris expected on May 6, 2022

April 1, 2022. Sanofi announced that the French Autorité des marchés financiers (AMF) has approved the listing prospectus prepared by EUROAPI in connection with the intended listing of its shares on the regulated market of Euronext Paris.

On March 17th, 2022, Sanofi’s Board of Directors unanimously decided to submit for approval to its shareholders the proposed distribution in kind (the “Distribution”) of EUROAPI shares, via an additional extraordinary dividend, exclusively in kind, in addition to the previously proposed €3.33 cash dividend per Sanofi share.

The Distribution relates to circa 58% of the share capital and voting rights of EUROAPI.

In connection with the proposed Distribution, EPIC Bpifrance has agreed to purchase 12% of EUROAPI shares from Sanofi, which confirmed its intention to hold circa 30% of the share capital and voting rights of the company after the Distribution.

The Distribution by Sanofi to its shareholders of EUROAPI shares in the form of an additional extraordinary dividend, exclusively in kind, is subject to the shareholders’ approval at Sanofi’s May 3, 2022 Ordinary and Extraordinary Shareholders’ Meeting.

Subject to certain customary exceptions, the following lock-up periods have been agreed:

  • 2 years for Sanofi and EPIC Bpifrance following the settlement and delivery of the EUROAPI shares to be sold to EPIC Bpifrance; and
  • 1 year for L’Oréal, Sanofi’s largest shareholder and for Karl Rotthier, CEO of the Company, following the settlement of the Distribution.

Main features of the Distribution are as follows:

  • The Distribution ratio will be one (1) EUROAPI share per twenty three (23) Sanofi shares.

No fractional EUROAPI shares will be issued. Any right to receive a fractional share will not be tradable or transferable.

Consequently, when the amount of the Distribution to which a Sanofi shareholder is entitled does not correspond to a whole number of EUROAPI shares (i.e., less than twenty three (23) or a multiple of twenty three (23) Sanofi shares), the shareholder will receive the immediately lower number of EUROAPI shares, plus a cash payment for the whole of the balance arising from the price at which EUROAPI shares corresponding to fractional shares were sold.

Each financial intermediary will sell the shares corresponding to the fractional shares of its entitled clients.

As a result, the amount of the cash balance may vary depending on the shareholder’s financial intermediary;

  • The technical reference price of EUROAPI shares is expected to be announced on May 5, 2022 by Euronext Paris after market close;
  • The admission to trading of the EUROAPI shares and the ex-date (détachement) of the Distribution will occur at 9.00 am (CET) on May 6, 2022;
  • The record date (the date on which positions are closed) for Sanofi shares to be eligible to the Distribution is scheduled on May 9, 2022;
  • Payment of the Distribution (delivery and book-entry of the allocated EUROAPI shares) will take place on May 10, 2022.

Following the Distribution and the purchase of 12% of EUROAPI shares by EPIC Bpifrance, the Sanofi group will no longer control EUROAPI, resulting in a slightly accretive impact on Sanofi 2022 business operating income (BOI) margin2.

Documents related to Sanofi shareholders’ meeting will be made available on April 11, 2022 on the Sanofi dedicated web page.

Investors are invited to read EUROAPI’s press release, issued concurrently and available on EUROAPI’s website announcing the AMF’s approval of its prospectus, and the listing prospectus in order to fully understand the potential risks and rewards associated with any decision to invest in EUROAPI shares.

EUROAPI draws attention to the risk factors contained in Chapter 3 and Section 22.2 of the listing prospectus.

The occurrence of one or more of these risks may have a significant adverse effect on the business, reputation, financial condition, results of operations or prospects of EUROAPI, as well as on the market price of EUROAPI’s shares.

For information on the tax treatment of the Distribution, shareholders are invited to read Paragraph 22.1.6 of the listing prospectus.

Copies of the French-language listing prospectus, approved by the AMF on March 31, 2022 under number 22-076, are available free of charge and on request from EUROAPI at EUROAPI’s registered office, 15 rue Traversière, 75012 Paris, France, as well as on the websites of the AMF (https://www.amf-france.org), Sanofi (https://www.sanofi.com) and EUROAPI (listing.euroapi.com).

An English-language information document for non-French resident shareholders of Sanofi is also available on Sanofi’s and EUROAPI’s website.

BNP Paribas, BofA Securities Europe SA, and J.P. Morgan SE are acting as Lead ECM Advisors to EUROAPI and Sanofi and Crédit Agricole Corporate and Investment Bank, Deutsche Bank, Natixis SA and Société Générale are acting as Other ECM Advisors in the contemplated listing. Rothschild & Co. is acting as independent financial adviser to Sanofi and EUROAPI. Jones Day is acting as a legal advisor to EUROAPI and Sanofi in connection with the Distribution, and White & Case as legal advisor to the Lead ECM Advisors.

Capital Markets Day details

Today, Sanofi will host a EUROAPI-dedicated Capital Markets Day at 1:30 pm CET and will cover the following topics:

  • Execution of the Play to Win strategy with the spin-off of EUROAPI
  • Main features of the Distribution
  • Sanofi’s long-term commitment to EUROAPI: strong business relationship and future ownership structure alongside with EPIC Bpifrance
  • EUROAPI’s deconsolidation impact for Sanofi
  • Presentation of EUROAPI, including its business model, strategy and guidance.

For background slides and webcast information, please refer to the following link on Sanofi website:https://www.sanofi.com/en/investors/financial-results-and-events/investor-presentations/Capital-Markets-Day-on-Euroapi-Webinar-2022.

About Sanofi
We are an innovative global healthcare company, driven by one purpose: we chase the miracles of science to improve people’s lives.

Our team, across some 100 countries, is dedicated to transforming the practice of medicine by working to turn the impossible into the possible.

We provide potentially life-changing treatment options and life-saving vaccine protection to millions of people globally, while putting sustainability and social responsibility at the center of our ambitions.”

https://www.sanofi.com/en/media-room/press-releases/2022/2022-04-01-07-30-00-2414527

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