FDA Extends Review of Merus' Zenocutuzumab for NRG1+ Cancers
Key Insights
The FDA has extended the review period for Merus' zenocutuzumab, a bispecific antibody targeting NRG1 (search) fusion-positive cancers, to February 4, 2025.
The delay is due to the FDA needing additional time to review Chemistry, Manufacturing, and Controls (CMC) information submitted by Merus.
The FDA has not requested additional clinical efficacy or safety data, nor raised concerns about the existing zenocutuzumab data package.
The FDA has extended the review period for Merus N.V.'s Biologics License Application (BLA) for zenocutuzumab, a bispecific antibody intended for the treatment of non-small cell lung cancer (search) (NSCLC) and pancreatic ductal adenocarcinoma (search) patients with NRG1 (search) fusions. The new target action date is set for February 4, 2025, moving from the original date of November 4, 2024.
The FDA's decision to extend the review is based on the need for "sufficient time" to assess additional Chemistry, Manufacturing, and Controls (CMC) information provided by Merus in response to an earlier request. Importantly, the FDA has not requested further clinical efficacy or safety data, nor has it indicated any issues with the existing data package for zenocutuzumab.
Zenocutuzumab: A Novel Approach to NRG1+ Cancers
Zenocutuzumab is a bispecific antibody designed to bind to the HER2 (search) protein and disrupt the interaction between the HER3 (search) receptor and neuregulin, or its associated fusion. This mechanism of action is believed to prevent the proliferation and survival of cancer cells. NRG1 (search) fusions, while rare, are oncogenic drivers found in various cancers.
Merus' BLA for zenocutuzumab was accepted by the FDA and granted Priority Review on May 6, 2024. The drug is being developed for NSCLC and pancreatic ductal adenocarcinoma (search) patients whose tumors harbor fusions of the NRG1 (search) gene.
Analyst Perspectives on the Delay
Truist Securities analyst Asthika Goonewardene noted that the FDA's questions appear to be related to a third-party manufacturer of zenocutuzumab and that the issues should have been anticipated and addressed earlier. Goonewardene's firm does not believe there is a serious underlying problem.
Leerink Partners analyst Andrew Berens suggested that the delay might put "pressure" on Merus' stock but does not expect it to have a significant impact on the company, as "zeno is not core to most investor's theses." Berens added, "We do not see readthrough to [petosemtamab] and the rest of the pipeline as this is limited to a manufacturing issue."
BMO Capital Markets analyst Etzer Darout echoed this sentiment, describing zenocutuzumab as a "modest commercial opportunity" for Merus, estimating peak sales of $462 million globally. Darout noted that Merus has expressed interest in potentially partnering the program, preferring to invest capital in the more promising petosemtamab. The delay "does not impact our MRUS thesis," Darout stated.
Merus' Broader Pipeline: Focus on Petosemtamab
Petosemtamab, a human, full-length IgG1 monoclonal antibody, targets EGFR (search) and LGR5 (search), both known cancer targets. It is designed to block EGFR signaling, prevent LGR-5-dependent internalization and degradation of EGFR in cancer cells, and enhance the body's anti-cancer response. Merus is currently developing petosemtamab for first-line treatment of head and neck squamous cell carcinoma (search), with a Phase III trial initiated in Q3 2024. Phase I/II data reported in May showed a 67% overall response rate in patients, regardless of PD-L1 expression levels. Petosemtamab is also being evaluated as a second-line treatment for metastatic colorectal cancer (search), with a Phase II study initiated in Q3.