December 19, 2022: “Sanofi and Innate Pharma SA announced an expansion of their collaboration, with Sanofi licensing a natural killer (NK) cell engager program targeting B7H3 from Innate’s ANKETTM (Antibody-based NK Cell Engager Therapeutics) platform.
Sanofi will also have the option to add up to two additional ANKETTM targets. Upon candidate selection, Sanofi will be responsible for all development, manufacturing and commercialization.
Innate and Sanofi signed a first NK cell engagers collaboration in 2016 for the generation and evaluation of up to two bispecific NK cell engagers, which are currently being evaluated by Sanofi’s R&D team, with one of these molecules already in clinical studies. . Valeria Fantin, Ph.D. Global Head of Oncology Research at Sanofi “At Sanofi, we are exploring the potential of NK cells for cancer immunotherapy, a key pillar for our oncology strategy.
Our relationship with Innate aligns with our commitment to work with promising French companies and supports our ambition to develop a diverse portfolio of next-generation NK cell engagers, highly synergistic with Sanofi’s allogeneic NK cell platform, engineered lymphokines that stimulate NK cells, and growing Immuno-oncology pipeline.
As a leading global company with roots in France, we are proud to collaborate to support the French healthcare ecosystem.”
Yannis Morel, Ph.D. Executive Vice President, Product portfolio strategy & Business development at Innate Pharma “Building on the success of our existing collaboration on hematologic targets, we are pleased to expand and strengthen our partnership with Sanofi on NK Cell Engagers with the addition of up to three new programs, including in solid tumors.
Sanofi’s investment in Innate further validate the value of ourANKETTM platform and its potential to address multiple tumor types.
By incorporating various tumor antigen binders, NK Cell Engagers are a versatile technology that may provide new options for patients and offer clinical benefit acrossmultiplecancers, whilst also maintaining a good safety profile.
This agreement also highlightsInnate’sstrategy to build a broad portfolio of ANKET programs addressing different types of cancer.”
Under the terms of the new license agreement, Innate will receive €25m upfront payment and up to €1.35bn total in preclinical, clinical, regulatory and commercial milestones plus royalties on potential net sales. Closing of the transaction is subject to HSR approval.
About 2016 Sanofi/Innate research collaboration and licensing agreement In 2016, Sanofi and Innate entered into a research collaboration and licensing agreement for the generation and evaluation of up to two bispecific NK cell engagers, using technology from Innate Pharma and Sanofi’s proprietary bispecific antibody format as well as tumor targets.
A Phase 1/2 clinical trial by Sanofi is ongoing, evaluating IPH6101/SAR’579 (SAR443579), the first NKp46/CD16-based CD123-targeted ANKETTM NK cell engager, in patients with relapsed or refractory acute myeloid leukemia (R/R AML), B-cell acute lymphoblastic leukemia (B-ALL) or high-risk myelodysplastic syndrome (HR-MDS).
In the summer 2022, Sanofi had made the decision to progress IPH6401/SAR’514 (SAR445514) into investigational new drug (IND)-enabling studies.
IPH6401/SAR’514 is a BCMA-targeting NK cell engager using Sanofi’s proprietary CROSSODILE® multi-functional platform, which comprises the Cross-Over-Dual-Variable-Domain (CODV) format.
It induces a dual targeting of the NK activating receptors, NKp46 and CD16, for an optimized NK cell activation, based on Innate’s ANKETTMproprietary platform.
Under the terms of the original license agreement, Sanofi is responsible for the development, manufacturing and commercialization of products resulting from the research collaboration.
Innate Pharma will be eligible to up to €400m in development and commercial milestone payments as well as royalties on net sales. To date, €13m milestone payments to Innate have been announced.”
December 19, 2022: “AstraZeneca and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan) has been approved in the European Union (EU) as monotherapy for the treatment of adult patients with advanced HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen.
Enhertu is a specifically engineered HER2-directed antibody drug conjugate (ADC) being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.
The approval by the European Commission follows the positive opinion of the Committee for Medicinal Products for Human Use in November 2022 and is based on results from the DESTINY-Gastric02 and DESTINY-Gastric01 Phase II trials.
In DESTINY-Gastric02, which enrolled patients from North America and Europe, treatment with Enhertu resulted in a confirmed objective response rate (ORR) of 41.8% as assessed by independent central review (ICR). Median duration of response (DoR) was 8.1 months.
In DESTINY-Gastric01, which enrolled patients from Japan and South Korea, treatment with Enhertu resulted in a confirmed ORR of 40.5% versus 11.3% with chemotherapy (irinotecan or paclitaxel) as assessed by ICR.
The median DoR was 11.3 months with Enhertu versus 3.9 months with chemotherapy.
Patients treated with Enhertu had a 41% reduction in the risk of death versus patients treated with chemotherapy (based on a hazard ratio of 0.59; 95% confidence interval: 0.39-0.88; p=0.0097) with a median overall survival (OS) of 12.5 months versus 8.4 months.
Approximately 136,000 cases of gastric cancer are diagnosed annually in Europe, where it represents the sixth leading cause of cancer death.
Gastric cancer is typically diagnosed in the advanced stage. Even when the disease is diagnosed at earlier stages, the survival rate remains modest.
Approximately one in five gastric cancers are HER2-positive.
Eric Van Cutsem, MD, PhD, Head of Department of Oncology at the University of Leuven, Belgium and Founding Chair of the ESMO-GI/World Congress of Gastrointestinal Cancers, said: “Today’s news is a welcome advance for patients with HER2-positive advanced gastric cancer.
Patients with this disease face poor outcomes following progression on initial treatment with a HER2-directed medicine as many do not respond to further treatment, and even those that do respond often do not have durable responses.
Data from the DESTINY-Gastric02 and DESTINY-Gastric01 trials support Enhertu becoming a new standard of care for patients in this setting.”
Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: “Today’s important approval makes Enhertu the first HER2-directed medicine to be approved for gastric cancer in the European Union in more than a decade.
Patients across the EU with advanced HER2-positive disease who have progressed following treatment in the first-line setting, may now have the opportunity to benefit from treatment with Enhertu.”
Ken Keller, Global Head of Oncology Business, and President and CEO, Daiichi Sankyo, Inc., said: “Enhertu is the first antibody drug conjugate to be approved in Europe for advanced gastric cancer, representing a major advance in treating this difficult-to-treat cancer.
With this approval, we can now offer patients with previously treated HER2-positive gastric cancer a treatment with clinically meaningful efficacy.”
In both trials, the safety profiles observed in patients treated with Enhertu were consistent with those seen in other trials of Enhertu with no new safety signals identified.
Enhertu is also approved in the US and several other countries for locally advanced or metastatic HER2-positive gastric cancer.”
December 08, 2022: “The U.S. FDA amended the emergency use authorizations (EUAs) of the updated (bivalent) Moderna and Pfizer-BioNTech COVID-19 vaccines to include use in children down to 6 months of age.
“More children now have the opportunity to update their protection against COVID-19 with a bivalent COVID-19 vaccine, and we encourage parents and caregivers of those eligible to consider doing so – especially as we head into the holidays and winter months where more time will be spent indoors,” said FDA Commissioner Robert M. Califf, M.D.
“As this virus has changed, and immunity from previous COVID-19 vaccination wanes, the more people who keep up to date on COVID-19 vaccinations, the more benefit there will be for individuals, families and public health by helping prevent severe illnesses, hospitalizations, and deaths.”
What parents and caregivers need to know:
Children 6 months through 5 years of age who received the original (monovalent) Moderna COVID-19 Vaccine are now eligible to receive a single booster of the updated (bivalent) Moderna COVID-19 Vaccine two months after completing a primary series with the monovalent Moderna COVID-19 Vaccine.
Children 6 months through 4 years of age who have not yet begun their three-dose primary series of the Pfizer-BioNTech COVID-19 Vaccine or have not yet received the third dose of their primary series will now receive the updated (bivalent) Pfizer-BioNTech COVID-19 vaccine as the third dose in their primary series following two doses of the original (monovalent) Pfizer-BioNTech COVID-19 Vaccine.
Children 6 months through 4 years of age who have already completed their three-dose primary series with the original (monovalent) Pfizer-BioNTech COVID-19 Vaccine will not be eligible for a booster dose of an updated bivalent vaccine at this time.
Children in this age group who already completed their primary series would still be expected to have protection against the most serious outcomes from the currently circulating omicron variant.
The data to support giving an updated bivalent booster dose for these children are expected in January. The agency is committed to evaluating those data as quickly as possible.
The Moderna and Pfizer-BioNTech bivalent COVID-19 vaccines include an mRNA component corresponding to the original strain to provide an immune response that is broadly protective against COVID-19 and an mRNA component corresponding to the omicron variant BA.4 and BA.5 lineages to provide better protection against COVID-19 caused by the omicron variant.
Individuals who receive the updated (bivalent) vaccines may experience similar side effects reported by individuals who received previous doses of the original (monovalent) mRNA COVID-19 vaccines.
The fact sheets for both bivalent COVID-19 vaccines for recipients and caregivers and for healthcare providers include information about the potential side effects, as well as the risks of myocarditis and pericarditis.
“Vaccines remain the best defense against the most devastating consequences of disease caused by the currently circulating omicron variant, such as hospitalization and death.
Based on available data, the updated, bivalent vaccines are expected to provide increased protection against COVID-19,” said Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research.
“Parents and caregivers can be assured that the FDA has taken a great deal of care in our review, and we encourage parents of children of any age who are eligible for primary vaccination or a bivalent COVID-19 vaccine booster dose to consider seeking vaccination now as it can potentially help protect them from COVID-19 during a time when cases are increasing.”
Moderna COVID-19 Vaccine, Bivalent
The monovalent Moderna COVID-19 Vaccine is authorized as a two-dose primary series in individuals six months of age and older and as a third primary series dose for individuals 6 months of age and older who have been determined to have certain kinds of immunocompromise.
With today’s authorization, the Moderna COVID-19 Vaccine, Bivalent is now authorized for administration in individuals 6 months through 5 years of age as a single booster dose at least 2 months after completion of primary vaccination with the monovalent Moderna COVID-19 Vaccine.
The Moderna COVID-19 Vaccine, Bivalent is also authorized for use in individuals 6 years and older as a single booster dose at least two months after completion of either primary vaccination with any authorized or approved COVID-19 vaccine, or receipt of the most recent booster dose with any authorized or approved monovalent COVID-19 vaccine.
For the authorization of a single booster dose of the Moderna COVID-19 Vaccine, Bivalent for children 6 months through 5 years of age, the FDA relied on immune response data that it had previously evaluated from a clinical study in adults of a booster dose of Moderna’s investigational bivalent COVID-19 vaccine that contained a component corresponding to the original strain of SARS-CoV-2 and a component corresponding to the omicron lineage BA.1.
In addition, the FDA conducted an analysis of data from a clinical study that compared the immune response among 56 study participants 17 months through 5 years of age who received a single booster dose of monovalent Moderna COVID-19 Vaccine at least six months after completion of a two-dose primary series of the vaccine to the immune response among approximately 300 study participants 18 through 25 years of age who had received a two-dose primary series of monovalent Moderna COVID-19 Vaccine in a previous study which determined the vaccine to be effective in preventing COVID-19.
The immune response to the booster dose of monovalent Moderna COVID-19 Vaccine in the 17 months through 5 years age group was comparable to the immune response to the two-dose primary series in the adult participants.
The safety of a single booster dose of the Moderna COVID-19 Vaccine, Bivalent for children 6 months through 5 years of age is supported by safety data from a clinical study which evaluated a booster dose of Moderna’s investigational bivalent COVID-19 vaccine (original and omicron BA.1), safety data from clinical trials which evaluated primary and booster vaccination with the monovalent Moderna COVID-19 Vaccine, and postmarketing safety data with the monovalent Moderna COVID-19 Vaccine and Moderna COVID-19 Vaccine, Bivalent.
In one clinical study, the safety of a single booster dose of monovalent Moderna COVID-19 Vaccine was evaluated in 145 clinical study participants 6 months through 5 years of age who received a booster dose of monovalent Moderna COVID-19 Vaccine at least six months after completion of the monovalent Moderna COVID-19 Vaccine two-dose primary series.
The most commonly reported side effects after a booster dose of the monovalent Moderna COVID-19 Vaccine across this age group included pain, redness and swelling at the injection site, swelling/tenderness of the lymph nodes of the injected arm or thigh, and fever.
In clinical study participants 17 months through 36 months of age, other commonly reported side effects included irritability/crying, sleepiness, and loss of appetite.
In clinical trial participants 37 months through 5 years of age, other commonly reported side effects included fatigue, headache, muscle pain, joint pain, chills, and nausea/vomiting.
The data accrued with the investigational Moderna bivalent COVID-19 vaccine (original and omicron BA.1) and with the monovalent Moderna COVID-19 Vaccine are relevant to the Moderna COVID-19 Vaccine, Bivalent because these vaccines are manufactured using the same process.”
December 07, 2022: “Member States of the World Health Organization today agreed to develop the first draft of a legally binding agreement designed to protect the world from future pandemics.
This “zero draft” of the pandemic accord, rooted in the WHO Constitution, will be discussed by Member States in February 2023.
Today’s agreement by the Intergovernmental Negotiating Body (INB), comprised of WHO’s 194 Member States, was a milestone in the global process to learn from the COVID-19 pandemic and prevent a repeat of the devastating impacts it has had on individuals and communities worldwide.
The INB gathered at WHO headquarters in Geneva from 5-7 December for its third meeting since its establishment in December 2021, following a special session of the World Health Assembly.
The Body today agreed that the INB’s Bureau will develop the zero draft of the pandemic accord in order to start negotiations at the fourth INB meeting, scheduled to start on 27 February 2023.
This draft will be based on the conceptual zero draft and the discussions during this week’s INB meeting.
The INB Bureau is comprised of six delegates, one from each of the six WHO regions, including the Co-Chairs Mr Roland Driece of the Netherlands and Ms Precious Matsoso of South Africa.
“Countries have delivered a clear message that the world must be better prepared, coordinated and supported to protect all people, everywhere, from a repeat of COVID-19,” said Mr Driece, Co-Chair of the INB Bureau.
“The decision to task us with the duty to develop a zero draft of a pandemic accord represents a major milestone in the path towards making the world safer.”
Fellow INB Bureau Co-Chair, Ms Matsoso, said government representatives stressed that any future pandemic accord would need to take into account equity, strengthen preparedness, ensure solidarity, promote a whole-of-society and whole- of-government approach, and respect the sovereignty of countries.
“The impact of the COVID-19 pandemic on human lives, economies and societies at large must never be forgotten,” said Ms Matsoso.
“The best chance we have, today, as a global community, to prevent a repeat of the past is to come together, in the spirit of solidarity, in a commitment to equity, and in the pursuit of health for all, and develop a global accord that safeguards societies from future pandemic threats.”
The WHO pandemic accord is being considered with a view to its adoption under Article 19 of the WHO Constitution, without prejudice to also considering, as work progresses, the suitability of Article 21.”
December 8, 2022: “Novartis announced the Phase III APPOINT-PNH study (NCT04820530) of investigational oral monotherapy iptacopan in complement-inhibitor-naïve (including anti-C5 therapies) adults with PNH met its primary endpoint.
Topline results showed a significant proportion of patients treated with iptacopan (200 mg twice daily) achieved clinically meaningful hemoglobin-level increases of 2 g/dL or more from baseline without the need for blood transfusions at 24 weeks.
In the study, the safety profile of iptacopan monotherapy was consistent with previously reported data.
Detailed data will be presented at an upcoming medical meeting and included as part of global regulatory submissions in 2023.
“We are very encouraged by the results of the complement-inhibitor-naïve data from the Phase III APPOINT-PNH trial,” said David Soergel, M.D., Global Head, Cardiovascular, Renal and Metabolism Development Unit, Novartis.
“This second iptacopan readout for PNH underscores the robust potential for this therapy, enabling us to submit a broad regulatory package with the goal of iptacopan potentially becoming the first oral monotherapy for PNH.”
Topline results for the pivotal Phase III APPLY-PNH study were recently announced.
It met its two primary endpoints, with iptacopan demonstrating superiority over anti-C5 therapies (eculizumab or ravulizumab) in adults with PNH experiencing residual anemia despite prior anti-C5 treatment.
The study showed a statistically significant and clinically meaningful increase in the proportion of iptacopan-treated patients achieving 2 g/dL or more hemoglobin-level increases from baseline, and 12 g/dL or more hemoglobin levels, both without the need for blood transfusions at 24 weeks, compared to anti-C5 therapies.
Novartis is grateful to the patients and clinical investigators whose time, trust and commitment made this PNH research possible, and is excited to continue to explore the potential of iptacopan as the first oral monotherapy option for patients with PNH.
Iptacopan is also being investigated in Phase III studies for the complement-mediated kidney diseases (CMKDs) C3 glomerulopathy (APPEAR-C3G [NCT04817618]), IgA nephropathy (APPLAUSE-IgAN [NCT04578834]), and atypical hemolytic uremic syndrome (APPELHUS [NCT04889430]), as well as in a number of additional indications in Phase II.
Following presentation of the Phase III APPLY-PNH iptacopan data at ASH, Novartis will host an investor conference call on December 13, 2022 at 18:30 CET / 12:30 ET.
A simultaneous webcast may be accessed by visiting the Novartis website
at https://www.novartis.com/investors/event-calendar, and a replay will be available after the call.
About the study APPOINT-PNH (NCT04820530) is a Phase III, multinational, multicenter, open-label, single-arm study to evaluate the efficacy and safety of twice-daily, oral iptacopan monotherapy (200 mg) in adult PNH patients who are naïve to complement inhibitor therapy, including anti-C5 therapies (e.g., eculizumab or ravulizumab).
The primary endpoint was to assess the proportion of participants achieving an increase in hemoglobin levels from baseline of 2 g/dL or more in the absence of red blood cell (RBC) transfusions at 24 weeks.
Secondary endpoints include the proportion of participants achieving sustained hemoglobin levels of 12 g/dL or more in the absence of RBC transfusions, transfusion avoidance defined as the proportion of participants who remain free from transfusions, average change in hemoglobin levels, average percent change in lactate dehydrogenase (LDH) levels, rate of breakthrough hemolysis, average change in absolute reticulocyte counts, change in fatigue, and rates of major adverse vascular events.
About paroxysmal nocturnal hemoglobinuria (PNH) PNH is a rare, chronic and serious complement-mediated blood disorder.
People with PNH have an acquired mutation in some of their hematopoietic stem cells (which are located in the bone marrow and can grow and develop into RBCs, white blood cells and platelets) that causes them to produce RBCs that are susceptible to premature destruction by the complement system.
This leads to intravascular hemolysis (destruction of RBCs within blood vessels) and extravascular hemolysis (destruction of RBCs mostly in the spleen and liver), which cause anemia (low levels of circulating RBCs), thrombosis (formation of blood clots), fatigue and other debilitating symptoms that can impact people’s quality of life.
It is estimated that approx. 10-20 people per million worldwide live with PNH. Although PNH can develop at any age, it is often diagnosed in people between 30-40 years old.
PNH has a significant unmet need not addressed by anti-C5 therapies (eculizumab or ravulizumab): despite treatment with anti-C5s, a large proportion of people with PNH remain anemic, fatigued and dependent on blood transfusions.
About iptacopan Iptacopan is an investigational first-in-class, orally administered targeted factor B inhibitor of the alternative complement pathway.
It acts upstream of the C5 terminal pathway, preventing not only intravascular but also extravascular hemolysis in PNH.
In doing so, iptacopan targets a key part of the biology responsible for PNH while offering an oral monotherapy option.
Discovered at the Novartis Institutes for BioMedical Research, iptacopan is currently in development for a number of other complement-mediated diseases (CMDs) where significant unmet needs exist, including kidney diseases C3G, IgAN, atypical hemolytic uremic syndrome (aHUS), membranous nephropathy (MN), lupus nephritis (LN), and blood disorders immune thrombocytopenic purpura (ITP) and cold agglutinin disease (CAD).”
December 07, 2022: “Updated results from the DESTINY-Breast03 Phase III trial showed that Enhertu (trastuzumab deruxtecan) demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) compared to trastuzumab emtansine (T-DM1) in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane.
These results and primary results from the DESTINY-Breast02 Phase III trial will be presented today at the 2022 San Antonio Breast Cancer Symposium (SABCS), with the updated results from DESTINY-Breast03 simultaneously published in The Lancet.
Enhertu is a specifically engineered HER2-directed antibody drug conjugate (ADC) being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.
In the key secondary endpoint analysis of OS for DESTINY-Breast03, Enhertu demonstrated a 36% reduction in risk of death versus T-DM1(based on a hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.47-0.87; p=0.0037).
In both treatment arms, median OS was not yet reached (Enhertu [40.5-NE] versus T-DM1 [34.0-NE]) after a median duration of follow-up of 28.4 months for Enhertu and 26.5 months for T-DM1.
An estimated 77.4% of patients were alive in the Enhertu arm at two years compared to 69.9% of patients treated with T-DM1.
The observed survival benefit was consistent across all analysed subgroups, including patients with or without baseline brain metastases, with or without baseline visceral disease, those who were hormone receptor (HR)-positive or HR-negative, and regardless of prior pertuzumab or lines of systemic therapy.
Sara Hurvitz, MD, Medical Oncologist, Professor of Medicine, and Director of the Breast Cancer Clinical Trials Program in the Division of Hematology-Oncology at the David Geffen School of Medicine at UCLA, and Medical Director for the Clinical Research Unit at the UCLA Jonsson Comprehensive Cancer Center in Santa Monica, CA, said: “The main goals of therapy for advanced breast cancer are to control the disease and improve survival, and it is therefore critical to continue to improve upon existing treatment options, particularly in the metastatic setting.
For patients with HER2-positive breast cancer who experience disease progression following initial treatment in the metastatic setting, Enhertu has shown significant improvement in survival compared to T-DM1, further confirming this medicine as the new standard of care.”
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “The updated results for DESTINY-Breast03 showing that Enhertu extends patients’ lives and also delays progression by nearly two years reinforces our belief that this medicine has the potential to set a new standard of care for patients with HER2-positive metastatic breast cancer treated in the second-line setting.
Complemented by DESTINY-Breast02, we now have two Phase III trials in HER2-positive metastatic breast cancer showing patients in these trials have more disease-free time and live longer when they receive Enhertu versus the previous standard of care.”
Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: “The overall survival benefits shown in both the DESTINY-Breast03 and DESTINY-Breast02 trials further validate the role of Enhertu in potentially extending the lives of patients with previously treated HER2-positive breast cancer.
Additionally, median progression-free survival was four times longer with one in five patients showing no detectable signs of disease when treated with Enhertu compared to T-DM1 in DESTINY-Breast03, which is particularly impressive in the metastatic setting of HER2-positive breast cancer.”
With the additional follow-up in DESTINY-Breast03, Enhertu also continued to demonstrate a clinically meaningful improvement in progression-free survival (PFS) with a 22 month improvement in median PFS over T-DM1, reaffirming the statistically significant finding at the previous interim analysis.
The updated exploratory analysis was not tested for statistical significance and not powered to show differences between treatment arms.
In this exploratory post-hoc analysis, the median PFS for patients in the Enhertu arm was 28.8 months compared to 6.8 months for T-DM1, as assessed by blinded independent central review (BICR).
Confirmed objective response rate (ORR) was 78.5% in the Enhertu arm with 21.1% of patients demonstrating a complete response (CR) versus an ORR of 35.0% in the T-DM1 arm, where 9.5% of patients achieved a CR.
The median duration of response (DoR) was 36.6 months in the Enhertu arm and 23.8 months in the T-DM1 arm.
Summary of updated results: DESTINY-Breast03
Efficacy Measure
Enhertu (5.4mg/kg)n=261
T-DM1 (3.6mg/kg)n=263
OS
Median OS (months) (95% CI)
Not reached (40.5-NE)
Not reached (34.0-NE)
Hazard ratio (95% CI)
0.64 (0.47-0.87)
p-value
p=0.0037i
OS rate (%) (95% CI)
12 months
94.1 (90.4-96.4)
86.0 (81.1-89.8)
24 months
77.4 (71.7-82.1)
69.9 (63.7-75.2)
PFS by BICR
Median PFS (months) (95% CI)
28.8 (22.4-37.9)
6.8 (5.6-8.2)
Hazard ratio (95% CI)
0.33 (0.26-0.43)
p-value
p<0.000001i,ii
Median PFS2 by investigatoriii
Median PFS2 (months) (95% CI)
40.5 (40.5-NE)
25.7 (18.5-34.0)
Hazard ratio (95% CI)
0.47 (0.35-0.62)
Confirmed ORR (%) (95% CI)
78.5 (73.1-83.4)
35.0 (29.2-41.1)
p-value
p<0.0001i,ii
Complete Response (%)
21.1%
9.5%
Partial Response (%)
57.5%
25.5%
Stable Disease (%)
18.0%
41.8%
Progressive Disease (%)
1.1%
17.9%
Median DoR (months) (95% CI)iv
36.6 (22.4-NE)
23.8 (12.6-34.7)
OS, overall survival; CI, confidence interval; PFS, progression-free survival; PFS2, second progression-free survival; BICR, blinded independent central review; ORR, objective response rate; DoR, duration of response i Two-sided ii Nominal p value. Updated exploratory analysis was not tested for statistical significance and not powered to show differences between treatment arms iii From the time of randomisation to second progression iv Based on BICR
The safety profile observed with Enhertu in DESTINY-Breast03 was consistent with previous clinical trials, with no new safety concerns identified.
The most common Grade 3 or higher treatment-related treatment-emergent adverse events (TEAEs) in the Enhertu arm were decreased neutrophil count (16.0%), anaemia (9.3%), decreased platelet count (7.8%) and nausea (7.0%).
There were 39 cases (15.2%) of treatment-related interstitial lung disease (ILD) or pneumonitis reported, as determined by an independent adjudication committee.
The majority (14.4%) were low grade (Grade 1 or Grade 2) with two Grade 3 (0.8%) events. No Grade 4 or Grade 5 ILD or pneumonitis events occurred.
DESTINY-Breast02 full results show significant improvements in PFS and OS versus chemotherapy in later-line HER2-positive metastatic breast cancer setting In primary results from the DESTINY-Breast02 Phase III trial,Enhertu demonstrated a 64% reduction in the risk of disease progression or death in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with T-DM1 versus physician’s choice of treatment (trastuzumab plus capecitabine or lapatinib plus capecitabine) [HR=0.36; 95% CI 0.28-0.45; p<0.000001].
The median PFS for patients in the Enhertu arm was 17.8 months versus 6.9 months for those in the physician’s choice of treatment arm, as assessed by BICR.
Enhertu also showed a 34% reduction in the risk of death compared to physician’s choice of treatment (HR=0.66; 95% CI 0.50-0.86; p=0.0021) with a median OS of 39.2 months versus 26.5 months.
The data from DESTINY-Breast02 confirms the data seen in the DESTINY-Breast01 Phase II trial which supported the first approvals of Enhertu in patients with HER2-positive metastatic breast cancer who have received two or more prior anti-HER2-based regimens.
The safety profile of Enhertu in DESTINY-Breast02 was consistent with previous clinical trials with no new safety concerns identified.
The most common Grade 3 or higher treatment-related TEAEs in the Enhertu arm were decreased neutrophil count (10.6%), anaemia (7.9%), neutropenia (7.7%) and nausea (6.7%).
There were 42 cases (10.4%) of treatment-related ILD or pneumonitis reported, as determined by an independent adjudication committee.
The majority (9.1%) were low grade (Grade 1 or Grade 2) with three Grade 3 (0.7%) events, no Grade 4 events and two (0.5%) Grade 5 ILD or pneumonitis events occurring.”
December 06, 2022: “Pfizer Inc. and Clear Creek Bio, Inc. announced a research collaboration and exclusive license agreement to advance the discovery and development of potential inhibitors of the SARS-CoV-2 papain-like protease (PLpro) for the oral treatment of COVID-19.
PLpro is an essential enzyme, which, along with the main protease (Mpro), plays an important role in viral replication.
This program will expand Pfizer’s innovative anti-infective pipeline and, if successful, will complement Pfizer’s existing portfolio of COVID-19 products with direct-acting antiviral agents against different SARS-CoV-2 targets.
“COVID-19 has proven to be a devastating and highly unpredictable disease, one with the potential to remain a global health concern for years to come,” said Charlotte Allerton, Chief Scientific Officer, Anti-Infectives and Head of Medicine Design, of Pfizer.
“It is critical that we try to stay ahead of the virus, continuing to advance clinical development opportunities for our current oral therapy as well as innovating through our internal programs and strategic partnerships to bring forward additional monotherapy and/or combination treatment candidates that we believe may play a role in the ongoing fight against COVID-19.”
“As COVID-19 continues to evolve, there is a significant need for oral antivirals with novel mechanisms of action,” said Vikram Sheel Kumar, M.D., Chief Executive Officer of Clear Creek Bio.
“We explored the druggable SARS-CoV-2 genome and identified PLpro as a promising and untapped target. Leveraging our team’s expertise and success in bringing novel drugs from idea to approval, we internally developed highly potent PLpro inhibitors.
We look forward to working with Pfizer, a global leader in antiviral development, to advance a new class of oral antivirals for COVID-19.”
Under the terms of the agreement, the two companies will work together to identify a PLpro candidate to progress into the clinic, at which time Pfizer will be solely responsible for further development and commercialization activities.
Clear Creek Bio will receive an undisclosed upfront payment and will be eligible to receive additional potential milestone payments plus royalties on future product sales.
About SARS-CoV-2 PLpro SARS-CoV-2 has two essential proteases, the main protease (Mpro) and the papain-like protease (PLpro), both required to fully process the viral polyprotein and assemble a functional replicase complex.
In addition to its critical role in viral replication, the PLpro also contributes to dysregulation of host innate immunity and immune evasion.”
December06,2022: “Bayer announced the U.S. launch of the Bayer Science Collaboration Explorer (BSCE) as part of its ongoing efforts to enhance public trust in scientific innovations, processes, and R&D activities.
The Explorer is a publicly accessible database where Bayer shares information on its science collaborations and new contracts with universities, public research institutions, and individuals.
Innovation is crucial to overcome the most pressing issues of our time, such as climate change, COVID-19, or the food crisis.
At Bayer, the company’s innovation ecosystem has produced breakthrough solutions to the world’s most complex challenges impacting humanity – and the company cannot do it alone.
Research collaborations are essential to develop and translate scientific findings, however partnerships between the public and private sector are sometimes regarded with skepticism.
In fact, only 29% of U.S. adults say they have a great deal of confidence in scientists to act in the best interests of the public, down from 39% in November 2020.
As science in general is facing eroding trust, Bayer is proactively addressing the desire for more transparency around corporate-funded research with clear, understandable, and accessible information for all stakeholders about the collaborations that are helping drive innovation for our society.
“Trust in science is essential for solving the major challenges humanity is facing and transparency is key to strengthening society’s trust in scientific innovations,” said Werner Baumann, CEO of Bayer AG.
“Launching the Bayer Science Collaboration Explorer in the United States demonstrates our commitment to transparency.
The publicly accessible database allows everyone to explore our external science collaborations. These partnerships are crucial to helping us achieve what matters to all of us and is anchored in Bayer’s vision ‘Health for All, Hunger for None.’”
Matthias Berninger, Executive Vice President of Public Affairs, Science & Sustainability at Bayer added: “Our commitment to transparency goes beyond just Bayer as a company – we want to drive this forward together with our industry, academic, and civil society partners.
We therefore see the launch of the Explorer as a game-changing tool to generate an important dialogue on trust in science.
As we lead this conversation, we welcome all stakeholders to join our work to enhance trust in the innovations that will address the biggest needs of our society.”
Specifically, the following core details will be published for new contracts: Name and country of the institution/person, collaboration type (e.g., research contract), subject of collaboration (e.g., oncology, digital farming), funding committed, effective date, participating Bayer division.
The Explorer is part of Bayer’s twelve transparency commitments. Complementing the Explorer, they provide open access to information from a variety of areas, including clinical trials and safety studies of Bayer’s crop protection products, or its political activities.”
December 06, 2022: “In July, I commissioned an external evaluation of the U.S. Food and Drug Administration’s Human Foods Program, including the Office of Food Policy and Response (OFPR), the Center for Food Safety and Applied Nutrition (CFSAN), as well as relevant parts of the Office of Regulatory Affairs (ORA).
The external evaluation External Link Disclaimer, conducted by an expert panel facilitated by the Reagan-Udall Foundation, was asked to assess the processes and procedures, resourcing, and organizational structure for the Foods Program.
Today, the panel released its findings and recommendations to the agency. I want to thank the panel and the Reagan-Udall Foundation for their work and for all those, including FDA staff and external stakeholders, who provided important feedback for the panel to consider.
Although we have not yet had an opportunity to review the full report in depth, it does provide significant observations and options for the agency’s consideration, reflecting important and diverse perspectives, which will be carefully considered.
The work of these independent evaluators will help to inform a new vision for the FDA Human Foods Program.
The agency is committed to providing a public update on the new vision at the end of January 2023 and additional public updates by the end of February 2023, including the planned leadership structure and any changes to key internal processes and procedures.
This new vision and structure will be built on the external evaluation being released today; the internal review of the agency’s infant formula supply chain response completed in September, which has already resulted in noticeable improvements in our operations across the Foods Program; and ongoing work that allows the agency to take advantage of emerging advances in food science, with a goal of designing a system that allows us to more quickly adapt to an ever- changing and evolving environment.
I will be making final decisions regarding the future of the FDA Human Foods Program after reviewing the report and consulting with stakeholders both externally and internally.
To assist me in this effort, I am forming a group of agency leaders to advise me on how best to implement and operationalize these findings.
I expect this leadership group to be bold and focused on the transformative opportunities ahead for the FDA’s food program – by fully realizing the preventive vision laid out in the Food Safety Modernization Act, elevating the importance of nutrition given declining life expectancy in the U.S., due in large part to chronic diseases, strengthening our state partnerships, and embracing innovative food and agricultural technologies that will allow us to supply the nation – and the globe – with ample safe and nutritious food in the decades ahead.
I will closely oversee the Human Foods Program until a determination is made on how we will strengthen and modernize the program.
I will be fully engaged to ensure that the program comes out of this transition with the resources, tools and visibility it warrants given how critical its work is to every American.
The Human Foods Program is a top priority for the agency. America’s food supply is as safe as it’s ever been, and our Foods Program experts have significantly contributed to the availability of more safe and nutritious food options for consumers.
That said, over the past several years, the program has been stressed by the increasing diversity and complexity of the nation’s food systems and supply chain, the ongoing impacts associated with climate change and rapid advances in the science underlying many of the foods we eat today.
Each of these factors point to the need to evolve our existing Foods Program leadership and structure and identify new ways to fund these mission critical activities.
In addition, the agency’s inspectional activities, including those conducted in collaboration with our state and international partners, are critical in order to assure a safe and high-quality food supply.
And finally, the need to maintain upgraded digital technology systems that allow us to stay ahead of the vast and growing food system, are essential components of any future plan.
I am fully committed to building a world-class Human Foods Program that works best for the public, our stakeholders and our employees – and that will allow us to effectively deliver on our mission.”
November 10, 2022: “After the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion for VidPrevtyn® Beta, the vaccine was approved by the European Commission, as a booster for the prevention of COVID-19 in adults 18 years of age and older.
Designed to provide broad protection against multiple variants, the protein-based COVID-19 booster vaccine is based on the Beta variant antigen and includes GSK’s pandemic adjuvant.
VidPrevtyn Beta is indicated as a booster for active immunization against SARS_CoV_2 in adults who have previously received an mRNA or adenoviral COVID vaccine. Shipments of VidPrevtyn Beta are ready to be distributed to European countries as per Advance Purchase Agreements.
Thomas Triomphe Executive Vice President, Vaccines, Sanofi “Today’s approvalvalidates our research in developing a novel solution for the COVID-19 pandemic.
As we’re ready to start first shipments, VidPrevtyn Beta will be an important new option to protect populations against multiple strains of COVID-19.”
Philip Dormitzer Global Head of Research and Development Vaccines, GSK “This EC approval is an important step in providing further vaccine solutions to Europe for the coming winter. Our protein-based, adjuvanted vaccine candidate has the potential to make an important contribution to public health as the pandemic evolves further.”
In registration studies, carried out at times when Omicron strains were predominantly circulating, the vaccine induced a strong immune response against multiple variants.
Registration studies included a Phase 3 primary efficacy trial (VAT08 Stage 2) and two separate immunogenicity studies, including one comparative study with approved mRNA booster as comparator.
About VidPrevtyn Beta VidPrevtyn Beta is a monovalent, recombinant-protein next-generation COVID-19 vaccine developed by Sanofi, modelled on the Beta variant and including GSK’s pandemic adjuvant. The same recombinant-protein technology is used in Sanofi’s approved seasonal flu vaccines. Next-generation COVID-19 vaccines are based on a variant-adapted approach, using a strain other than the parental strain of SARS-CoV-2 (D614 strain).
About COVIBOOST Immunogenicity & Safety Study The independent COVIBOOST (VAT013) study conducted by the Assistance Publique – Hôpitaux de Paris (AP-HP) investigated VidPrevtyn Beta following primary vaccination with two doses of Pfizer-BioNTech’s Comirnaty vaccine (BNT162b2). VidPrevtyn Beta generated a higher immune response (as measured by neutralizing antibody titers) than Pfizer-BioNTech’s booster or the Sanofi-GSK first-generation booster, both of which target the original D614 parent strain.
In this study, which included 247 adult subjects (18-73 years-old), all three vaccines also elicited neutralizing antibodies against the Omicron BA.1 variant, with highest responses generated by the Sanofi-GSK next-generation candidate, one month after injection.
VidPrevtyn Beta also elicited around 2.5 times more neutralizing antibodies against Omicron BA.1 and, in an exploratory analysis, against BA.4 / BA.5 strains than mRNA COVID-19 booster comparator.
About the VAT02 Immunogenicity & Safety Study Immunogenicity studies included VAT02 Cohort 2 and COVIBOOST which evaluated the booster formulation modelled on the Beta variant and including GSK’s pandemic adjuvant.
In the Phase 3 VAT02 Cohort 2 study, the vaccine induced (at day 15 following booster vaccination) a significant boost in antibody titers above baseline against multiple variants of concern (13-fold increase against D614 parent virus, 34-fold increase against the COVID-19 Beta strain) in 18-55 years-old adults previously primed with mRNA COVID-19 vaccines.
In the VAT02 cohort 2 study, reactions were mostly mild to moderate, transient and self resolutive.
About the VAT08 Stage 2 Efficacy & Safety Study The VAT08 Phase 3 Stage 2 study is a randomized, double-blind, placebo-controlled trial investigating primary vaccination with a bivalent COVID-19 vaccine containing both parental (D614) and Beta strains.
The results showed a 64.7% efficacy against symptomatic SARS-CoV-2 infection in adults, regardless of their SARS-CoV-2 infection status prior to vaccination, and 75.1% efficacy in participants previously infected with SARS-CoV-2.
This study was the first ever to report efficacy data in an Omicron environment.
Across all the above-mentioned studies, the Sanofi-GSK bivalent next-generation vaccine candidate was well-tolerated, with an acceptable safety profile.
About BARDA support Research and development for VidPrevtyn are supported by U.S. federal funds from the Biomedical Advanced Research and Development Authority (BARDA), Administration for Strategic Preparedness and Response at the U.S. Department of Health and Human Services under Contract # HHSO100201600005I, and in collaboration with the U.S. Department of Defense Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense under Contract # W15QKN-16-9-1002, and the National Institute of Allergy and Infectious Diseases (NIAID).”
November 11, 2022: “AstraZeneca announced the availability of the first rare disease therapy from Alexion, AstraZeneca’s Rare Disease group, in China.
The availability of Soliris (eculizumab) for the treatment of paroxysmal nocturnal haemoglobinuria (PNH) and atypical haemolytic uraemic syndrome (aHUS) in adults and children in China represents a significant expansion of the company’s global footprint in rare disease, following the acquisition of Alexion Pharmaceuticals, Inc. in 2021.
In addition to announcing the availability of Soliris, AstraZeneca announced that the National Medicine Products Administration of China (NMPA) has accepted its supplementary application for Soliris for the treatment of adults with refractory generalised myasthenia gravis (gMG) in patients who are anti-acetylcholine receptor (AchR) antibody positive.
The NMPA has also granted AstraZeneca approval to start ongoing, global clinical trials in China for investigational therapies being evaluated for the treatment of lupus nephritis (LN), immunoglobulin A nephropathy (IgAN) and light chain (AL) amyloidosis.
Marc Dunoyer, Chief Executive Officer, Alexion, said: “These milestones represent significant progress against our commitment to expand access to our rare disease medicines globally, including the introduction of innovative rare disease therapies in China.
Expanding access to our medicines is possible because of the combined strength of Alexion’s rare disease expertise and AstraZeneca’s vast global footprint, and we look forward to continue bringing our therapies to people living with rare diseases around the world in the future.”
Leon Wang, Executive Vice President, International and China President of AstraZeneca, said: “This milestone reflects our ambition to bring transformative, rare disease medicines to the significant number of patients and families living with rare diseases in China who currently have limited treatment options or no available treatment at all.
We look forward to advancing our commitment in China and aim to bring additional, innovative therapies to even more rare disease patients across the country.”
As the first C5 complement inhibitor, Soliris works by inhibiting the C5 protein in the terminal complement cascade, a part of the body’s immune system. Soliris is approved for multiple indications in many countries around the world.
The availability of Soliris in China provides people living with PNH or aHUS with a new treatment option that can reduce disease symptoms and prevent the dysregulated complement system from causing further damage.
AstraZeneca established a rare disease business unit in China in September 2021.
In the future, the company aims to introduce more innovative medicines in China, targeting the complement system and beyond, for the treatment of rare diseases including PNH, aHUS, gMG, neuromyelitis optica spectrum disorder (NMOSD), hypophosphatasia, IgAN, LN and amyloidosis.”
October05,2022: “Bayer has completed the sale of its Environmental Science Professional business to the international private equity firm Cinven, after the two companies had entered into a corresponding agreement in March.
The conditions for closing the transaction – including the receipt of regulatory approval – have now been met.
The purchase price for the business, which generated sales of approximately 600 million euros in 2021, amounts to 2.6 billion U.S. dollars (2.6 billion euros).
“We thank the employees of Environmental Science Professional for their many years of commitment and the associated success of Bayer.
In Cinven, we have found a strong new owner with a firm commitment to the long-term growth potential of the business and to its people,” said Rodrigo Santos, member of the Board of Management of Bayer AG and head of the Crop Science Division.
“At the same time, we can concentrate on our core agricultural business and the successful implementation of our growth strategy in the Crop Science Division.” Bayer will use the net proceeds from the transaction to reduce its net financial debt.
The divested business is set to operate as an independent company called Envu.
The business is a global leader offering solutions to control pests, disease and weeds in non-agricultural areas such as vector control, professional pest management, vegetation management, forestry, and turf and ornamentals.
It is headquartered in Cary, North Carolina, United States, and is active in over 100 countries. Nearly 900 employees in total will transfer from Bayer to Envu.
“Envu is a global leader in a highly attractive and critical industry.
We thank Bayer for the trust they have placed in Cinven and plan to build on the strong foundations established by Bayer by significantly investing in it,” said Pontus Pettersson, Partner at Cinven.
“Cinven is excited to build an independent, focused company and is well positioned to continue to drive innovation and accelerate growth, including the delivery of digital and data-enabled solutions, and to extend the product portfolio further by creating innovative and sustainable solutions for its customers.”
