FDA Rejects Regeneron's Lymphoma Therapy Odronextamab for Second Time

Regeneron's lymphoma therapy odronextamab has been rejected by the FDA for the second time. The company disclosed this information in its Q2 2025 financials. The FDA sent a complete response letter, and Regeneron will now have the opportunity to address the concerns raised by the regulators. The rejection comes as a setback for the company, which had high hopes for the therapy.

Regeneron Pharmaceuticals (REGN) has faced another setback with its lymphoma therapy odronextamab. The U.S. Food and Drug Administration (FDA) declined to approve the drug for the second time, as disclosed in the company's Q2 2025 financials. 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 [1].

Odronextamab, a CD20 x CD3 bispecific antibody, had previously been rejected by the FDA in March 2024 due to concerns over the enrollment status of its confirmatory trials. The latest rejection is unrelated to safety or efficacy concerns, but rather to manufacturing issues at Catalent's Indiana facility [2]. This facility is responsible for the final stages of drug preparation and packaging for both odronextamab and Regeneron's high-dose Eylea [3].

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 [1]. Despite the FDA's rejections, odronextamab received regulatory approval in the European Union for the treatment of patients with relapsed/refractory follicular lymphoma and diffuse large B-cell lymphoma in August 2024 [4].

The rejection of odronextamab is 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. The ongoing phase 3 OLYMPIA-1 trial for odronextamab is expected to provide further data to support the drug's approval [4].

References:
[1] https://www.biopharmadive.com/news/regeneron-odronextamab-crl-allogene-patient-death-bristol-myers-earnings/756464/
[2] https://www.reuters.com/business/healthcare-pharmaceuticals/us-fda-declines-approve-regenerons-blood-cancer-therapy-second-time-2025-08-01/
[3] https://seekingalpha.com/news/4476790-regeneron-lymphoma-therapy-rejected-fda
[4] https://www.onclive.com/view/fda-issues-crl-for-odronextamab-in-relapsed-refractory-follicular-lymphoma