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Pfizer Announces FDA and EMA Acceptance of Etrasimod Regulatory Submissions for Ulcerative Colitis

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Pfizer Announces FDA and EMA Acceptance of Etrasimod Regulatory Submissions for Ulcerative Colitis

December 21, 2022: “Pfizer announced that the U.S. FDA has accepted for review a New Drug Application (NDA) for etrasimod for individuals living with moderately-to-severely active ulcerative colitis (UC).

The FDA’s decision is expected in the second half of 2023. The European Medicines Agency (EMA) has also accepted the Marketing Authorization Application (MAA) for etrasimod in the same patient population with the decision anticipated in the first half of 2024.

Etrasimod is an oral, once daily, selective sphingosine-1-phosphate (S1P) receptor modulator designed for optimized pharmacology and engagement of S1P receptors 1, 4, and 5. In addition to UC, it is being investigated for a range of other immuno-inflammatory diseases.

UC is a chronic and often debilitating condition that affects an estimated 3.8 million people in North America and Europe.

Symptoms of UC can include chronic diarrhea with blood and mucus, abdominal pain, and urgency.

UC can have a significant effect on work, family, and social activities. There is a need for additional advanced therapeutic options in UC that are oral, effective, and have a favorable risk-benefit profile.

“Ulcerative colitis can substantially impact the day-to-day lives of people living with this chronic and often debilitating disease, and many patients never achieve nor maintain remission on today’s therapies,” said Michael Corbo, PhD, Chief Development Officer, Inflammation & Immunology, Pfizer Global Product Development.

“We believe that etrasimod, if approved, has the potential to be a best-in-class, first-line advanced therapy for people living with moderately-to-severely active ulcerative colitis, based on its clinical profile.”

These submissions were based on previously announced results from the ELEVATE UC Phase 3 registrational program (ELEVATE UC 52 and ELEVATE UC 12) that evaluated the safety and efficacy of etrasimod 2 mg once daily on clinical remission in UC patients who had previously failed or were intolerant to at least one conventional, biologic, or Janus kinase (JAK) inhibitor therapy.

Both randomized, double-blind, placebo-controlled studies achieved all primary and key secondary endpoints, with a safety profile consistent with previous studies.

About ELEVATE UC 52 and ELEVATE UC 12
ELEVATE UC 52 and ELEVATE UC 12 are pivotal trials that are part of the ELEVATE UC Phase 3 registrational program.

ELEVATE UC 52 is a randomized, double-blind, placebo-controlled trial that utilized a treat-through design comprising of a 12-week induction period followed by a 40-week maintenance period.

Beginning at week 12, all patients could continue their randomized treatment; patients whose disease had not improved or had worsened compared to baseline could discontinue and, if eligible, enroll in an open-label extension study.

The primary objective of this trial was to assess the safety and efficacy of etrasimod 2 mg once daily on clinical remission after both 12 and 52 weeks. The primary endpoint is based on the 3-domain, modified Mayo score (MMS).

In ELEVATE UC 52, clinical remission was 27.0% for patients receiving etrasimod compared to 7.4% for patients receiving placebo at week 12 (19.8% differential, P≤.001) and was 32.1% compared to 6.7% at week 52 (25.4% differential, P≤.001).

Statistically significant improvements were attained in all key secondary endpoints, including endoscopic improvement, symptomatic remission, and mucosal healing at weeks 12 and 52, and corticosteroid-free remission and sustained clinical remission at week 52.

ELEVATE UC 12 is a randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of etrasimod 2 mg once-daily in subjects with moderately-to-severely active UC.

The primary objective of this trial was to assess the safety and efficacy of etrasimod on clinical remission at 12 weeks assessed by the FDA-required, 3-domain, MMS.

In ELEVATE UC 12, clinical remission was achieved among 24.8% of patients receiving etrasimod compared to 15.2% of patients receiving placebo (9.7% differential, P=.0264).

All key secondary endpoints were met at week 12, including endoscopic improvement, symptomatic remission, and mucosal healing.

In ELEVATE UC 12, a similar proportion of patients experienced treatment-emergent adverse events (AEs) between etrasimod 2 mg and placebo treatment groups, while in ELEVATE UC 52, it was higher in the etrasimod 2 mg group compared to placebo. The proportion of patients experiencing serious AEs was similar between treatment groups in both trials.

The most common treatment-emergent AEs in 3% or more of etrasimod-treated patients and greater than placebo up to week 52 in either trial were headache, worsening of UC, COVID-19 infection, dizziness, pyrexia, arthralgia, abdominal pain and nausea.

There were no reports of bradycardia or atrioventricular block as serious AEs. Data support initiation of etrasimod treatment does not require complex up-titration regimen.

Nearly two-thirds of patients in ELEVATE UC 52 and ELEVATE UC 12, respectively, were naïve to biologic or JAK inhibitor therapy.”

https://www.pfizer.com/news/press-release/press-release-detail/pfizer-announces-fda-and-ema-acceptance-etrasimod

FDA Approves New HIV Drug for Adults with Limited Treatment Options

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FDA Approves New HIV Drug for Adults with Limited Treatment Options

December 22, 2022: “The U.S. Food and Drug Administration approved Sunlenca (lenacapavir), a new type of antiretroviral medication for adult patients living with human immunodeficiency virus type 1 (HIV-1), whose HIV infections cannot be successfully treated with other available treatments due to resistance, intolerance, or safety considerations.

After the starting dose is completed, Sunlenca is administered as subcutaneous (under the skin) injections once every six months, allowing convenient dosing for patients.

“Today’s approval ushers in a new class of antiretroviral drugs that may help patients with HIV who have run out of treatment options,” said Debra Birnkrant, M.D., director of the Division of Antivirals in the FDA’s Center for Drug Evaluation and Research.

“The availability of new classes of antiretroviral medications may possibly help these patients live longer, healthier lives.”

Sunlenca is the first of a new class of drugs called capsid inhibitors to be FDA-approved for treating HIV-1.

Sunlenca works by blocking the HIV-1 virus’ protein shell (the capsid), thereby interfering with multiple essential steps of the viral lifecycle.

Sunlenca’s starting dose is given as oral tablets and subcutaneous injections, followed by maintenance injections every six months; Sunlenca is given in combination with other antiretroviral(s). 

The safety and efficacy of Sunlenca were established through a multicenter clinical trial with 72 patients whose HIV infections were resistant to multiple classes of HIV medications.

These patients had to have high levels of virus in their blood despite being on antiretroviral drugs.

Patients were enrolled into one of two study groups. One group was randomized to receive either Sunlenca or placebo in a double-blind fashion, and the other group received open-label Sunlenca.

The primary measure of efficacy was the proportion of patients in the randomized study group who achieved a certain level of reduction in virus during the initial 14 days compared to baseline.

In this group, 87.5% of patients who received Sunlenca achieved such a decrease in virus compared to 16.7% of patients who received a placebo.

After 26 weeks of Sunlenca plus other antiretrovial drugs, 81% of participants in the first group achieved HIV RNA suppression, where levels of HIV were low enough to be considered undetectable.

After 52 weeks, 83% of participants continued to have HIV RNA suppression.

The most common adverse reactions with Sunlenca were injection site reactions and nausea. Most injection site reactions were described as swelling, pain or redness. Sunlenca comes with certain warnings and precautions.

Injection site reactions described as nodules or indurations may be persistent in some patients.

Additional warnings and precautions include the risk of developing immune reconstitution syndrome, which is when the immune system overreacts after starting HIV treatment.

Also, small (residual) amounts of Sunlenca can remain in the body for up to a year or longer; low levels of drug caused by missing doses of Sunlenca or failing to maintain a fully suppressive HIV treatment regimen after stopping Sunlenca could lead to an increased risk of developing viral resistance.

Residual amounts of Sunlenca could also lead to potential drug interactions.

Patients should not receive Sunlenca if they also take certain drugs that cause reduced levels of Sunlenca. This may result in losing virologic response and developing viral resistance. 

The FDA granted Sunlenca Priority Review, Fast Track and Breakthrough Therapy designations for this indication. 

The FDA granted the approval of Sunlenca to Gilead Sciences.”

https://www.fda.gov/news-events/press-announcements/fda-approves-new-hiv-drug-adults-limited-treatment-options

Lynparza with abiraterone approved in EU for metastatic castration-resistant prostate cancer

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Lynparza with abiraterone approved in EU for metastatic castration-resistant prostate cancer

December 21, 2022: “AstraZeneca and MSD’s Lynparza (olaparib) in combination with abiraterone and prednisone or prednisolone has been approved in the European Union for the treatment of metastatic castration-resistant prostate cancer (mCRPC) in adult men for whom chemotherapy is not clinically indicated.

This approval by the European Commission was based on results from the PROpel Phase III trial and follows the positive recommendation in the EU by the Committee for Medicinal Products for Human Use in November 2022.

In the trial, Lynparza in combination with abiraterone and prednisone or prednisolone, reduced the risk of disease progression or death by 34% versus abiraterone and prednisone or prednisolone (based on a hazard ratio [HR] of 0.66; 95% confidence interval [CI] 0.54-0.81; p<0.0001).

Median radiographic progression-free survival (rPFS) was 24.8 months for Lynparza plus abiraterone versus 16.6 months for abiraterone alone.

Furthermore, a planned rPFS analysis by blinded independent central review (BICR) showed Lynparza plus abiraterone had a median rPFS of 27.6 months compared to 16.4 months with abiraterone alone, extending median rPFS by almost one year.

Updated results from a second planned analysis presented at ESMO 2022 showed a favourable trend towards improved overall survival with Lynparza plus abiraterone versus abiraterone alone (based on HR of 0.83; 95% CI 0.66-1.03; p=0.11), however, the difference did not reach statistical significance at the time of this data cut-off (analysis at 40% data maturity).

Prostate cancer is the most common cancer in men in Europe, with an estimated 473,000 patients diagnosed and 108,000 deaths in 2020.

Overall survival for patients with mCRPC is approximately three years in clinical trial settings, and even shorter in the real-world.

Approximately half of patients with mCRPC may receive only one line of active treatment, with diminishing benefit of subsequent therapies.

Noel Clarke, Urological Surgeon and Professor of Urological Oncology at Manchester’s Christie/Salford Royal Hospitals and Manchester University, a senior investigator of the PROpel trial, said: “The results of the PROpel Phase III trial of olaparib in combination with abiraterone as a first-line treatment show that this therapeutic combination can provide significant clinical benefit to patients with metastatic castration-resistant prostate cancer.

Patients with this condition in the EU will now, for the first time, have the opportunity to benefit from this new treatment combination.”

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: “Many patients with metastatic castration-resistant prostate cancer are only able to receive one line of active therapy, as the disease can progress quickly. 

Lynparza in combination with abiraterone has been shown to reduce the risk of disease progression by 34% versus the standard of care treatment in the PROpel trial.

Moreover, the combination of Lynparza with abiraterone as a first-line treatment expands the use of Lynparza to a broader group of metastatic castration-resistant prostate cancer patients than those treated with Lynparza alone in the second-line setting in the PROfound trial.

Today’s approval marks a significant advance toward addressing the unmet need of patients with metastatic castration-resistant prostate cancer in the EU.”

Dr. Eliav Barr, Senior Vice President, Head of Global Clinical Development and Chief Medical Officer, MSD Research Laboratories, said: “MSD is committed to developing new treatment options for patients with metastatic castration-resistant prostate cancer, a complex disease that urgently needs more therapies.

This approval by the European Commission marks another step towards delivering on that commitment and we look forward to extending the benefits of Lynparza to more patients with metastatic castration-resistant prostate cancer in the EU.”

The safety and tolerability of Lynparza in combination with abiraterone in PROpel was in line with that observed in prior clinical trials and the known profiles of the individual medicines.

There was no increase in the rate of discontinuation of abiraterone in patients treated with Lynparza in combination with abiraterone and no detrimental effect on health-related quality of life versus those treated with abiraterone alone (Functional Assessment of Cancer Therapy-Prostate questionnaire).

In August, supplemental New Drug Application (sNDA) for Lynparza in combination with abiraterone and prednisone or prednisolone was accepted and granted Priority Review in the US for the treatment of adult patients with mCRPC.

The Prescription Drug User Fee Act (PDUFA) date is anticipated during the first quarter of 2023.

Lynparza is approved in the US based on results from the PROfound Phase III trial as monotherapy for patients with homologous recombination repair (HRR) gene-mutated mCRPC (BRCA and other HRR gene mutations) who have progressed following prior treatment with enzalutamide or abiraterone; and in the EU, Japan, and China for patients with BRCA-mutated mCRPC who have progressed following prior therapy that included a new hormonal agent.

Financial considerations
Following this approval for Lynparza in the EU, AstraZeneca will receive a regulatory milestone payment from MSD of $105m, anticipated to be booked as Collaboration Revenue by the Company during the fourth quarter of 2022.”

https://www.astrazeneca.com/media-centre/press-releases/2022/lynparza-approved-in-eu-for-prostate-cancer.html

Imfinzi plus chemotherapy approved in EU for patients with advanced biliary tract cancer

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Imfinzi plus chemotherapy approved in EU for patients with advanced biliary tract cancer

December 21, 2022: “AstraZeneca’s Imfinzi (durvalumab) has been approved in the European Union (EU) for the 1st-line treatment of adult patients with unresectable or metastatic biliary tract cancer (BTC) in combination with chemotherapy (gemcitabine plus cisplatin).

The approval by the European Commission was based on the primary results from the TOPAZ-1 Phase III trial published in the New England Journal of Medicine Evidence, and on the updated results presented at the European Society for Medical Oncology Congress 2022.

The approval follows the recommendation by The Committee for Medicinal Products for Human Use of the European Medicines Agency in November 2022.

At the interim analysis, Imfinzi plus chemotherapy reduced the risk of death by 20% versus chemotherapy alone (based on a hazard ratio [HR] of 0.80; 95% confidence interval [CI] 0.66-0.97; p=0.021).

Updated results from TOPAZ-1 after an additional 6.5 months of follow-up showed a 24% reduction in the risk of death versus chemotherapy alone (HR 0.76; 95% CI, 0.64-0.91), with more than two times as many patients treated with Imfinzi plus chemotherapy estimated to be alive at two years versus chemotherapy alone (23.6% versus 11.5%).

Updated median overall survival (OS) was 12.9 months versus 11.3 with chemotherapy.

BTC is a group of rare and aggressive cancers that occur in the bile ducts (cholangiocarcinoma) and gallbladder.

There are approximately 211,000 new patients diagnosed with gallbladder and biliary tract cancer each year, and about 40,000 of these occur across Europe.

These patients have a poor prognosis, with approximately 5% to 15% of patients with BTC surviving five years.

Juan W. Valle, MD, Professor of Medical Oncology at the University of Manchester and The Christie NHS Foundation Trust, UK, and a lead investigator in the TOPAZ-1 Phase III trial, said: “Today’s approval marks an important shift in the treatment of this aggressive and often overlooked disease and a significant improvement compared to standard of care for these patients.

After waiting over a decade for new therapeutic options, biliary tract cancer patients in the EU will now have the opportunity to benefit from an immunotherapy-based treatment for the first time.”

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: “With this approval, Imfinzi plus chemotherapy becomes the only immunotherapy-based treatment option available to patients in the EU with advanced biliary tract cancer.

This approval underscores our commitment to transform survival outcomes while addressing the high unmet need for new and improved treatments for patients with hepatobiliary cancers.”

Imfinzi plus chemotherapy was generally well tolerated, with no new safety signals observed, and did not increase the discontinuation rate due to adverse events (AEs) compared to chemotherapy alone.

Grade 3 or 4 treatment-related AEs were experienced by 60.9% of patients treated with Imfinzi plus chemotherapy, and by 63.5% of patients treated with chemotherapy alone.

Imfinzi plus chemotherapy is approved in the US and other countries for the treatment of adults with locally advanced or metastatic BTC.

Regulatory applications are also currently under review in Japan and several other countries based on the TOPAZ-1 results.”

https://www.astrazeneca.com/media-centre/press-releases/2022/imfinzi-approved-in-eu-for-biliary-tract-cancer.html

FDA Provides Update on External Evaluation to Strengthen Agency’s Tobacco Program

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FDA Provides Update on External Evaluation to Strengthen Agency’s Tobacco Program

December 19, 2022: “Earlier this year, I commissioned an external evaluation External Link Disclaimer of the U.S. Food and Drug Administration’s Tobacco Program, to be conducted by an external expert panel facilitated by the Reagan-Udall Foundation, led by former FDA Chief of Staff Lauren Silvis.

The panel was asked to assess the Tobacco Program’s regulatory processes and agency operations relating to regulations and guidance, application review, compliance and enforcement and communication with the public and other stakeholders.

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. 

Over the next several weeks, Center for Tobacco Products leadership will closely review the report’s findings and recommendations, in consultation with the Commissioner’s Office, to determine next steps and will provide an update by early February.

Importantly, since joining the FDA as the director for the Center for Tobacco Products in July, Brian King, Ph.D., M.P.H., has continued to build on the work of his predecessors while also implementing changes to best position the center for success moving forward.

This work is particularly critical as we focus on preventing initiation, while also helping people quit, especially the deadliest form of tobacco use, combustible tobacco products. Despite meaningful declines in cigarette use over the past several decades, nearly 500,000 Americans still die every year from cigarette smoking.

Additionally, with more than 3 million youth reporting current use of a tobacco product in 2022, and e-cigarettes being the most used product, we risk another generation becoming addicted to these products. 

While we consider potential improvements to our operations and processes for tobacco product regulation, we are committed to communicating any changes with clarity and transparency for our many stakeholders.

For the FDA to build on this work in the ever-evolving tobacco marketplace, it’s also critical to ensure CTP has what it needs to adequately and efficiently address the recommendations in the report. 

We’ve made important progress and reached science-based regulatory decisions across a broad array of products in the 13 years since Congress tasked the FDA with regulating tobacco products.

And as I’ve noted previously, even greater challenges and opportunities lie ahead as we determine how the agency will navigate complex policy issues and determine enforcement activities for an increasing number of novel products that could potentially have significant impact on public health. 

The hardworking and talented individuals in CTP, and across the FDA, deserve the best support possible so they can fulfill their strong commitment to public health – and the American public that we serve.

It is my belief that this effort will continue strengthening the FDA and better position the agency to deal with the many immediate public health issues related to tobacco products we are facing, while preparing for challenges and opportunities in the future.”

https://www.fda.gov/news-events/press-announcements/fda-provides-update-external-evaluation-strengthen-agencys-tobacco-program

Federal Court Enters Consent Decree Against Oklahoma Drug Compounder

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Federal Court Enters Consent Decree Against Oklahoma Drug Compounder

December 19, 2022: “The U.S. District Court for the Western District of Oklahoma entered a consent decree against Qualgen LLC, an outsourcing facility with a history of violations.

The consent decree prohibits the company from directly or indirectly distributing adulterated drugs in interstate commerce.

The consent decree entered against Qualgen, its majority owner, Shaun Riney, and its Director of Quality, Jasen Lavoie, follows a complaint filed by the U.S. Department of Justice on behalf of the U.S. Food and Drug Administration.

The complaint asserts that Qualgen introduced into interstate commerce adulterated drugs that were manufactured, processed, packed or held under conditions that violate current good manufacturing practice (CGMP) requirements. 

“While drugs compounded by outsourcing facilities are not subject to pre-market review and approval by the FDA for safety and effectiveness, they must comply with rigorous manufacturing quality assurance requirements,” said Jill P. Furman, J.D., acting director of the Office of Compliance in the FDA’s Center for Drug Evaluation and Research.

“The FDA’s commitment to ensuring compliance with current good manufacturing practice requirements is a critical protection for patients. We will remain vigilant and hold all manufacturers accountable to best protect the public health.” 

Under section 503B of the Federal Food, Drug, and Cosmetic Act (FD&C Act), a compounder can register as an outsourcing facility, which is defined as a facility at one geographic location or address that is engaged in the compounding of sterile drugs, has elected to register as an outsourcing facility and complies with all the requirements of section 503B of the FD&C Act.

Qualgen is registered with the FDA as an outsourcing facility. 

Drugs compounded by an outsourcing facility can qualify for exemptions from FDA approval requirements and the requirement to label products with adequate directions for use, but not from CGMP requirements. 

The agency inspected and cited Qualgen for violations of CGMP requirements during several inspections since 2015, issuing a safety alert in 2015 and a warning letterExternal Link Disclaimer in 2016.

The FDA’s most recent inspection of Qualgen’s Oklahoma facilities ended in September 2022. Qualgen manufactures and ships compounded drugs from its Oklahoma facilities.

Compounded drugs can serve an important role for patients whose medical needs cannot be met by an FDA-approved drug product.

Compounded drugs are not approved by the FDA and, therefore, have not been evaluated for safety or efficacy.

The case was filed by the U.S. Department of Justice’s Consumer Protection Branch, on behalf of the FDA.”

https://www.fda.gov/news-events/press-announcements/federal-court-enters-consent-decree-against-oklahoma-drug-compounder

Sanofi and Innate Pharma expand collaboration for natural killer cell therapeutics in oncology

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Sanofi and Innate Pharma expand collaboration for natural killer cell therapeutics in oncology

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.
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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 our ANKETTM 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 across multiple cancers, whilst also maintaining a good safety profile. 

This agreement also highlights Innate’s strategy 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.”

https://www.sanofi.com/en/media-room/press-releases/2022/2022-12-19-06-00-00-2575893

Enhertu approved in EU for patients with previously treated HER2-positive advanced gastric cancer

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Enhertu approved in EU for patients with previously treated HER2-positive advanced gastric cancer

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.”

https://www.astrazeneca.com/media-centre/press-releases/2022/enhertu-approved-in-eu-for-gastric-cancer.html

FDA Authorizes Updated (Bivalent) COVID-19 Vaccines for Children Down to 6 Months of Age

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FDA Authorizes Updated (Bivalent) COVID-19 Vaccines for Children Down to 6 Months of Age

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.”

https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-updated-bivalent-covid-19-vaccines-children-down-6-months

WHO Member States agree to develop zero draft of legally binding pandemic accord in early 2023

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WHO Member States agree to develop zero draft of legally binding pandemic accord in early 2023

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.”

https://www.who.int/news/item/07-12-2022-who-member-states-agree-to-develop-zero-draft-of-legally-binding-pandemic-accord-in-early-2023

Novartis investigational iptacopan provides clinically meaningful increases in hemoglobin levels in complement-inhibitor-naïve patients with PNH

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Novartis investigational iptacopan provides clinically meaningful increases in hemoglobin levels in complement-inhibitor-naïve patients with PNH

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).”

https://www.novartis.com/news/media-releases/novartis-investigational-iptacopan-provides-clinically-meaningful-increases-hemoglobin-levels-complement-inhibitor-naive-patients-pnh

AZ and Daiichi Sankyo’s Enhertu improved progression-free survival by 22 months vs.T-DM1

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AZ and Daiichi Sankyo’s Enhertu improved progression-free survival by 22 months vs.T-DM1

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=261T-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-valuep=0.0037i
OS rate (%) (95% CI) 
      12 months94.1 (90.4-96.4)86.0 (81.1-89.8)
      24 months77.4 (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-valuep<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-valuep<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)iv36.6 (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.”

https://www.astrazeneca.com/media-centre/press-releases/2022/enhertu-achieved-statistically-significant-overall-survival.html

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