An Endocrine News roundup of the week’s pharmaceutical news, breakthroughs, and general information. *
Priority Review Granted for HER2-low or HER2-ultralow Metastatic Breast Cancer Treatment
On October 1, AstraZeneca and Daiichi Sankyo announced that its supplemental Biologics License Application (sBLA) for ENHERTU® (fam-trastuzumab deruxtecan-nxki) has been accepted and granted Priority Review in the US for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2 ultralow (IHC 0 with membrane staining) breast cancer who have received at least one endocrine therapy in the metastatic setting based on positive results from the DESTINY-Breast06 Phase III trial which compared ENHERTU to chemotherapy.
The Food and Drug Administration (FDA) grants Priority Review to applications for medicines that, if approved, would offer significant improvements over available options by demonstrating safety or efficacy improvements, preventing serious conditions or enhancing patient compliance. The Prescription Drug User Fee Act date, the FDA action date for their regulatory decision, is anticipated during the first quarter of 2025.
ENHERTUwas also recently granted Breakthrough Therapy Designation (BTD) by the FDA in this setting. BTD accelerates the development and regulatory review of potential new medicines intended to treat a serious condition and address a significant unmet medical need.
HR-positive, HER2-negative is the most common breast cancer subtype, accounting for approximately 70% of all breast cancers. Despite being classified as HER2-negative, many of these tumors still carry some level of HER2 expression. It is estimated that up to 85-90% of tumors historically classified as HR-positive, HER2-negative may be HER2-low or HER2-ultralow.
Susan Galbraith, executive vice president, Oncology R&D, AstraZeneca, said: “While endocrine therapies are widely used in the initial treatment of HR-positive metastatic breast cancer, most patients see limited benefit with additional lines of treatment, and subsequent chemotherapy is often associated with poor response rates and outcomes. The results from DESTINY-Breast06 show thatENHERTUhas the potential to evolve the current HR-positive treatment landscape and become the first targeted treatment for patients with HER2-low or HER2-ultralow expression following endocrine therapy.”
Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: “This Priority Review highlights the potential to expand the existing indication of ENHERTU in HER2-low metastatic breast cancer to include use in an earlier disease setting as well as in a broader patient population that includes HER2-ultralow. We look forward to working closely with the FDA with the goal of bringing ENHERTU to more patients as quickly as possible.”
The sBLA is based on data from the DESTINY-Breast06 Phase III trial presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting and recently published in The New England Journal of Medicine.
In the trial, ENHERTU reduced the risk of disease progression or death by 37% by blinded independent central review (BICR) versus chemotherapy (hazard ratio [HR] 0.63; 95% confidence interval [CI]: 0.53-0.75; p< 0.0001) in the overall trial population. Median PFS was 13.2 months with ENHERTUcompared to 8.1 months with chemotherapy.
Results were consistent between patients with HER2-low expression and HER2-ultralow expression. In the primary endpoint analysis of patients with HER2-low expression, ENHERTU showed a median PFS of 13.2 months compared to 8.1 months for chemotherapy (HR 0.62; 95% CI 0.51-0.74; p<0.0001). In a prespecified exploratory analysis of patients with HER2-ultralow expression, ENHERTU showed a median PFS of 13.2 months versus 8.3 months, respectively (HR 0.78; 95% CI 0.50-1.21).
The safety profile of ENHERTU in DESTINY-Breast06 was consistent with previous clinical trials of ENHERTUin breast cancer with no new safety concerns identified.
ENHERTU is a specifically engineered HER2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialized by AstraZeneca and Daiichi Sankyo.
ENHERTUis already approved in more than 65 countries, including the US, for patients with HER2-low metastatic breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.
Amneal and Metsera Announce Strategic Collaboration to Develop and Supply Portfolio of Next-Generation Medicines for Obesity and Metabolic Diseases
On October 1, Amneal Pharmaceuticals, Inc., and Metsera, Inc., a clinical-stage biopharmaceutical company accelerating the next generation of medicines for obesity and metabolic diseases, announced that they have entered into a collaboration agreement to enable the efficient development and large-scale supply of a portfolio of new weight loss medicines globally.
The collaboration positions Amneal and Metsera to deliver weight loss and metabolic disease medicines at scale. Among other compelling aspects of the collaboration, it is important to know that:
- Metsera is advancing a portfolio of next-generation therapies for obesity and metabolic diseases, including ultra-long acting injectable and oral nutrient stimulated hormone (NuSH) analogs and combinations designed with best-in-class profiles. With a library of over 20,000 NuSH peptide analogs and peptide/antibody conjugates, Metsera aims to address the increasing demand and future needs of the highly dynamic global obesity and diabetes landscape across a broad range of modalities.
- Metsera recently announced highly competitive results from the Phase 1 clinical trial of its glucagon-like peptide-1 (GLP-1) receptor agonist injectable, MET-097. The randomized, placebo-controlled, double-blind Phase 1 trial demonstrated that MET-097 achieved significant and durable weight loss. MET-097 is expected to be the first drug manufactured under Amneal and Metsera’s collaboration.
- Amneal is expediting its entry into the rapidly growing global obesity market while leveraging its core competencies: science-driven product development, high-quality and cost-effective manufacturing, and the ability to rapidly scale-up and execute.
Under the terms of the agreement, Amneal will serve as Metsera’s preferred supply partner for developed markets, including the United States and Europe. Amneal will also be granted a license to commercialize Metsera’s products in select emerging markets, including India and certain countries in Southeast Asia, Africa, and the Middle East.
Amneal will construct two new greenfield manufacturing facilities in India, one for peptide synthesis and one for sterile fill-finish manufacturing. The new site, which will house both facilities, is expected to break ground later this year, with a total net cost to Amneal of between $150 million and $200 million over the next four to five years, net of contributions from Metsera and government incentives. Additionally, Amneal will support Metsera with certain product development activities, including drug substance manufacturing, product formulation and drug-device development.
“GLP-1s and other breakthrough obesity therapies have significant and wide-ranging health benefits for patients. Amneal is deeply committed to providing access to high-quality, affordable and essential medicines, including those in new categories. Through this strategic collaboration, we have the opportunity to extend our mission to a new portfolio of injectable and oral weight loss therapies. We are excited to work with Metsera and apply Amneal’s deep expertise in complex pharmaceutical manufacturing to bring these programs to market,” said Chirag and Chintu Patel, Co-Chief Executive Officers of Amneal.
Whit Bernard, Chief Executive Officer of Metsera, said, “With this collaboration, we have secured high-quality development and commercial scale capacity for our broad portfolio of ultra-long-acting injectable and oral NuSH analogs. Collaborating with Amneal brings dedicated access to unique capabilities and capacity not typically available to biotech firms at an early stage. These comprise access to Amneal’s drug substance manufacturing, product formulation and drug-device development capabilities, including its in-house API and sterile fill-finish, through both established and new state-of-the-art facilities.”
*Inclusion in Pharma Fridays does not suggest an endorsement by Endocrine News or the Endocrine Society.
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