FDA Accepts Odronextamab BLA in Relapsed/Refractory Follicular Lymphoma

• The FDA accepted resubmission of the biologics license application (BLA) of odronextamab (Ordspono) for review for treating relapsed/refractory (R/R) follicular lymphoma (FL) after at least 2 lines of systemic therapy.
• A Prescription Drug User Fee Act target action date of July 30, 2025, has been set for the FDA decision.
• Data from the phase 1 ELM-1 and pivotal phase 2 ELM-2 trials (NCT02290951; NCT03888105) support this resubmission.

The FDA has accepted the resubmission of the BLA for odronextamab, a CD20xCD3 bispecific antibody, for the treatment of R/R FL.¹

This decision follows the achievement of an FDA-mandated enrollment target for the phase 3 confirmatory trial, OLYMPIA-1 (NCT04501666), which was the sole approvability issue identified in the FDA’s complete response letter (CRL) to the previous submission in March 2024.

The resubmission is supported by findings from the phase 1 ELM-1 and pivotal phase 2 ELM-2 trials, which demonstrated an 80% overall response rate (ORR; n = 103) and a 74% complete response (CR) rate in patients with R/R FL (n = 95). For those achieving CR, the median duration of response was 25 months (95% CI, 20-not evaluable [NE]).^2,3

“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 Sabarish Ram Ayyappan, MD, medical director of hematologic malignancies, City of Hope Cancer Treatment Center in Atlanta, Georgia, in an interview with Targeted Oncology.

For safety, serious adverse events occurred in 67% of patients, with the most common (≥10%) being cytokine release syndrome, COVID-19, and pneumonia.

Odronextamab’s Mechanism of Action

Odronextamab is a bispecific antibody designed to target CD20 on cancer cells and CD3 on T cells.¹ 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 R/R FL or diffuse large B-cell lymphoma (DLBCL) who have received at least 2 prior lines of systemic therapy.⁴ However, its safety and efficacy remain under evaluation by other regulatory authorities, including the FDA.

Ongoing Clinical Trials and Development Program

Odronextamab is currently being evaluated in a comprehensive clinical development program, including¹:

ELM-1 trial: An ongoing, phase 1 study to assess its safety and tolerability in patients with CD20-positive B-cell malignancies who have previously received CD20-directed antibody therapy. (NCT02290951)

ELM-2 trial: A phase 2 trial investigating odronextamab across 5 independent cohorts, including DLBCL, FL, mantle cell lymphoma, marginal zone lymphoma, and other B-NHL subtypes. The primary end point of the trial ORR, with secondary end points including CR, progression-free survival (PFS), overall survival (OS), and duration of response (DOR). (NCT03888105)

OLYMPIA-1 trial: A phase 3 confirmatory trial comparing odronextamab monotherapy with rituximab (Rituxan) plus standard-of-care chemotherapies for the treatment of patients with R/R FL. (NCT06091254)

OLYMPIA-2 trial: A separate phase 3 trial evaluating odronextamab in combination with chemotherapy vs rituximab plus standard-of-care chemotherapies. (NCT06097364)

REFERENCES:

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

2. Tessoulin B, Choo SG, Taszner M, et al. Maintenance of moderate to high levels of functioning and quality of life with odronextamab monotherapy in patients with relapsed or refractory follicular lymphoma. Blood. 2023;142(1):669. doi:10.1182/blood-2023-181942.

3. Ayyappan S, Kim WS, Kim TM, et al. Final analysis of the phase 2 ELM-2 study: Odronextamab in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Blood. 2023;142(1):436. doi:10.1182/blood-2023-179818.

4. 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 February 26, 2025. https://tinyurl.com/ybffrkf3