European Regulatory Committee Recommends Rejecting Puma Biotechnology’s Breast Cancer Medicine
The European Medicines Agency (EMA)’s Committee for Medicinal Products for Human Use (CHMP) offered a negative opinion on Puma Biotechnology’s application for neratinib for breast cancer.
The committee took a negative vote, which typically means the EMA will reject the application at a subsequent meeting. Puma has the option to request a re-examination of the opinion if the company submits a request within 15 days. The company indicates it plans to submit the request.
Neratinib was being evaluated for the extended adjuvant treatment of early stage HER2-positive breast cancer. The application was based on results from the Phase III ExteNET trial and the Phase II CONTROL trial.
Nerlynx (neratinib) is a kinase inhibitor indicated for early-stage HER2 overexpressed or amplified breast cancer after adjuvant trastuzumab-based therapy. The drug was approved by the U.S. Food and Drug Administration in July 2017 for that indication.
The CHMP apparently felt that although the drug decreased the risk of cancer returning, there were doubts how that benefit would play out in actual clinical practice. It also noted side effects, particularly diarrhea, that were difficult to manage.
Puma had already received preliminary news of the decision in late-January, causing the stock to drop by about 30 percent at that time.
The EMA isn’t obligated to follow the recommendations of CHMP, although they usually do.
Earlier this month, Puma inked an exclusive licensing deal with CANBridge Life Sciences to develop and commercialize Neratinib in China, Hong Kong, Macau and Taiwan. Under the deal, Puma is paying CANbridge $30 million upfront and an additional $40 million based on regulatory approval and commercialization steps.
“Puma is committed to providing access to Nerlynx to patients around the world, and greater China represents a very large market opportunity,” said Alan Auerbach, founder and chief executive officer of Puma, in a statement at the time.
And late last year, on December 12, 2017, Puma announced that it would join Tokyo, Japan-based Daiichi Sankyo, Inc. in a preclinical research collaboration with Memorial Sloan Kettering Cancer Center (MSK) in evaluating the combination of Daiichi Sankyo’s antibody drug conjugate DS-8201 and Puma’s neratinib in HER2-mutated or HER2-positive solid tumors.
DS-8201 is the lead product in Daiichi Sankyo’s ADC Franchise. ADCs deliver cytotoxic chemotherapy payloads to cancer cells using a linker attached to a monoclonal antibody. DS-8201 is a “smart chemotherapy” made up of humanized HER2 antibody attached to a topoisomerase I inhibitor payload via a tetrapeptide-based linker.
A group of scientists led by Maurizio Scaltriti and Bob Li of MSK will utilize isogenic models to establish patient-derived xenograft models to evaluate the drug combinations in various tumor types.
“Since early clinical data suggest that DS-8201 may have activity beyond breast and gastric cancers, the archetype HER2-driven tumors, we are interested in studying this asset on a molecular level as well as in combination with other HER2-targeting agents,” said Tom Held, vice president, Daiichi Sankyo’s Global Head, Antibody Drug Conjugate Task Force, in a statement. “In this collaboration, we are examining whether combining DS-8201 and neratinib, with its specific covalent binding to the HER2 receptor and associated increased internalization, is a rational combination therapy strategy to pursue. We are excited to join forces with Memorial Sloan Kettering and Puma to advance the understanding of combining HER2-targeted therapies to potentially treat various forms of HER2-mutated cancer.”