For a Second Time, FDA Denies Approval of Odronextamab in Lymphoma

The FDA has issued a complete response letter (CRL) for the biologics license application (BLA) of odronextamab (Ordspono) for the treatment of relapsed/refractory follicular lymphoma following 2 or more lines of systemic therapy.¹ The CRL cited issues with a site inspection.

In March 2024, the FDA issued 2 CRLs to the odronextamab BLA.² These CRLs were related to the enrollment status of confirmatory trials that are evaluating the agent. There were no issues regarding the efficacy or safety of odronextamab, as well as no issues regarding trial design, labeling, or manufacturing.

Initially, the FDA granted priority review to the BLA seeking the approval of odronextamab in September 2023, supported by findings from the phase 1 ELM-1 (NCT02290951) and phase 2 ELM-2 (NCT03888105) trials.³

At the 2023 American Society of Hematology Annual Meeting, data from the final analysis of the ELM-2 trial were reported, demonstrating that at a median follow-up for efficacy of 29.9 months (range, 20.4–32.6), the objective response rate among the 127 patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) who were naive to CAR T-cell therapy was 52%. The complete response rate was 31.5%, and the median duration of response was 10.2 months (95% CI, 5.0–17.9).²

In his presentation, Sabarish Ram Ayyappan, MD, medical director of hematologic malignancies, City of Hope Cancer Treatment Center in Atlanta, Georgia, noted that response data for odronextamab were consistent with results from the phase 1 ELM-1 trial (NCT02290951) of the safety and efficacy of odronextamab in patients with relapsed or refractory non-Hodgkin lymphoma.³

“The responses were durable with a median duration of complete response up to 18 months. At 24 months, the CR rate was maintained in 47% of the patients. The safety of the drug also was evaluated and consistent with previous reports that odronextamab is safe in patients who received them with relapsed/refractory diffuse large B-cell lymphoma,” explained Ayyappan in an interview with Targeted Oncology.

Following the 2024 CRLs, Regeneron, the sponsor, resubmitted the BLA for odronextamab in follicular lymphoma in February 2025.⁴

About Odronextamab

Odronextamab is a bispecific antibody designed to target CD20 on cancer cells and CD3 on T cells. The agent facilitates T-cell activation and localized cancer-cell killing. Using this mechanism, odronextamab leverages the immune system to target and eliminate malignant B cells.

In the European Union, odronextamab is approved by the European Medicines Agency for the treatment of patients with relapsed/refractory follicular lymphoma or DLBCL who have received at least 2 prior lines of systemic therapy.⁵ However, its safety and efficacy remain under evaluation by other regulatory authorities, including the FDA.

REFERENCES:

1. Regeneron Reports Second Quarter 2025 Financial and Operating Results. News release. Regeneron. August 1, 2025. Accessed August 6, 2025. https://tinyurl.com/bdz4e7ex

2. Regeneron provides update on biologics license application for odronextamab. News release. Regeneron. March 25, 2024. Accessed August 6, 2025. https://tinyurl.com/38dhaxh6

3. Odronextamab BLA for treatment of relapsed/refractory follicular lymphoma (FL) and diffuse large b-cell lymphoma (DLBCL) accepted for FDA priority review. News release. Regeneron Pharmaceuticals, Inc. September 29, 2023. Accessed August 6, 2025. https://tinyurl.com/386ne2xe

4. Odronextamab BLA accepted for FDA review for the treatment of relapsed/refractory follicular lymphoma. News release. Regeneron Pharmaceuticals, Inc. February 26, 2025. Accessed August 6, 2025. https://tinyurl.com/5fakt6vb

5. Ordspono (odronextamab) approved in the European Union for the treatment of relapsed/refractory follicular lymphoma and diffuse large B-cell lymphoma. News release. Regeneron Pharmaceuticals, Inc. August 26, 2024. Accessed August 6, 2025. https://tinyurl.com/ybffrkf3