The U.S. Food and Drug Administration has declined to approve Regeneron Pharmaceuticals' lymphoma therapy odronextamab for the second time, the company disclosed in its Q2 2025 financials on Friday. The rejection centers on manufacturing issues at a third-party facility rather than concerns about the drug's safety or efficacy.
Manufacturing Issues Drive Latest Rejection
The FDA sent a complete response letter (CRL) to Regeneron citing issues discovered during an inspection at a third-party manufacturing site operated by Catalent, which was recently acquired by Novo Nordisk. The Catalent Indiana facility is responsible for the final stages of drug preparation and packaging for both odronextamab and Regeneron's high-dose Eylea.
This latest rejection differs significantly from the first FDA denial in March 2024, which was based on concerns over the enrollment status of confirmatory trials. The current manufacturing-related issues represent a new regulatory hurdle for the CD20 x CD3 bispecific antibody.
European Approval Provides Regulatory Precedent
Despite the FDA setbacks, odronextamab received regulatory approval in the European Union in August 2024 for the treatment of patients with relapsed/refractory follicular lymphoma and diffuse large B-cell lymphoma. This approval demonstrates that regulatory authorities have found the therapy's risk-benefit profile acceptable when manufacturing standards are met.
Path Forward Requires Manufacturing Resolution
Regeneron is now required to address the issues raised by the FDA and resubmit its biologics license application (BLA) for odronextamab. The company has expressed frustration and exhaustion with the repeated regulatory setbacks but remains optimistic about the drug's potential.
The ongoing phase 3 OLYMPIA-1 trial for odronextamab is expected to provide further data to support the drug's approval. This trial continues to generate evidence for the therapy's efficacy in treating lymphoma patients.
The rejection represents a significant setback for Regeneron, which had high hopes for the therapy. However, the company has shown resilience in the face of regulatory challenges and continues to invest in its pipeline development.
