The U.S. FDA’s Oncologic Drugs Advisory Committee (ODAC) convened on September 26 to scrutinize the application of PD-1 inhibitors in oncology, particularly focusing on Bristol Myers Squibb’s (NYSE: BMY) Opdivo (nivolumab) and Merck, Sharp & Dohme’s (NYSE: MRK) Keytruda (pembrolizumab). The committee evaluated the risk-benefit profile of these drugs for unresectable or metastatic gastric and gastroesophageal junction adenocarcinoma (GC/GEJ), and metastatic esophageal squamous cell carcinoma (ESCC). The central topic was whether the use of PD-L1 biomarker expression should dictate the usage of these drugs for the aforementioned indications. Additionally, the committee reviewed BeiGene’s (NASDAQ: BGNE; HKG: 6160; SHA: 688235) Biologics License Application (BLA) for its PD-1 inhibitor Tevimbra (tislelizumab) which is also seeking approvals for the same two types of cancer.
In the FDA’s briefing documents, scientists proposed that the approval scope of PD-1 drugs for GC/GEJ and ESCC might need to be confined to patients with high PD-L1 expression. This measure aims to prevent the administration of anti-PD-1 therapy to patients who are unlikely to benefit, given the potential for harm, including serious immune-related adverse events. The committee concluded with a vote of 10-2, with one abstention, suggesting that Keytruda and Opdivo do not provide benefits to PD-L1-negative patients for the indications in question.
While the ODAC’s recommendations are advisory, they often influence FDA decisions, suggesting a probable revision to the labeling information for Keytruda and Opdivo. Currently, both drugs are approved in the U.S. as first-line treatments for HER2-negative unresectable or metastatic GC/GEJ, irrespective of PD-L1 expression. Should the FDA approve BeiGene’s Tevimbra, the ODAC’s findings may result in a more restrictive label for this drug as well.- Fineline.com
