FDA Accepts Odronextamab BLA Resubmission for R/R Follicular Lymphoma

Support for the application comes from the efficacy data reported in the phase 1 ELM-1 and phase 2 ELM-2 trials.

The FDA has accepted a resubmission of the biologics license application (BLA) for odronextamab (Ordspono) as a treatment for patients with relapsed/refractory follicular lymphoma following at least 2 lines of prior systemic therapy, according to a news release from the drug’s developer, Regeneron Pharmaceuticals, Inc.1

The target Prescription Drug User Fee Act (PDUFA) date is July 30, 2025.

The decision follows the attainment of an FDA-mandated enrollment target for the confirmatory phase 3 OLYMPIA-1 trial (NCT06091254), which was the sole approvability issue in the complete response letter associated with the previous submission. Support for the decision comes from efficacy data shown in the phase 1 ELM-1 (NCT02290951) and phase 2 ELM-2 trials (NCT03888105).

ELM-2 Trial

According to data published in Annals of Oncology, at a median follow-up of 20.1 months, the objective response rate (ORR) by independent review committee (IRC) assessment was 80% (n = 103/128; 95% CI, 72.5%-86.9%), with a complete response (CR) rate of 73%.2 Additionally, per investigator assessment, the ORR and CR rates were 82% and 73%, respectively. Furthermore, 95% of patients experienced tumor reductions.

By week 12, 88% (n = 91/103) of responders had attained at least a partial response (PR), 5 of whom converted to a CR before 28 weeks of treatment. The median time to response was 2.7 months (range, 1.8-7.9), and the median duration of response (DOR) was 22.6 months (95% CI, 17.7 months-not estimable [NE]). Additionally, the median duration of CR was 25.1 months (95% CI, 20.5-NE), and the probability of maintaining a CR for 12 months was 75.0%.

Efficacy was observed across all prespecified subgroups. Of note, patients with disease progression within 24 months of first-line treatment (POD24) had an ORR and CR rate of 81% and 73%. Additionally, among patients who received prior autologous stem-cell transplantation (ASCT), the rates were 85% and 77%, respectively. For patients who had received at least 4 or 5 prior lines of therapy, respectively, the ORRs were 73% and 64%, and the CR rates were 66% and 59%.

The median progression-free survival (PFS) was 20.7 months (95% CI, 17.2-27.5), and the 12-, 18-, and 24-month PFS rates were 66.2%, 57.5%, and 46.1%, respectively. The median overall survival (OS) was not reached (NR, 95% CI, 32.4-NE), with 12- and 24-month OS rates of 86.2% and 70.1%, respectively. Among patients who attained a CR, the median PFS was 27.8 months (95% CI, 23.0-NE), and the median OS was NR (95% CI, 40.4-NE).

In the open-label ELM-2 trial, adult patients with relapsed/refractory B-cell non-Hodgkin lymphoma received 80 mg of intravenous odronextamab in 21-day cycles, with maintenance dosing consisting of 160 mg of the agent every 2 weeks until disease progression or protocol-defined treatment-discontinuation criteria. Investigators administered step-up dosing to help manage the risk of severe cytokine release syndrome (CRS).

“[T]his study has demonstrated the compelling, durable efficacy and generally manageable safety of odronextamab in [relapsed/refractory follicular lymphoma,]” Tae Min Kim, MD, professor of Internal Medicine at the Seoul National University College of Medicine and member of the Neuro-Oncology Team at the Seoul National University Hospital, wrote in the publication with coninvestigators.2 “These results support further investigation of odronextamab in [follicular lymphoma] as monotherapy and in combination with other agents. Phase 3 trials of odronextamab in the earlier-line setting are ongoing.”

ELM-1 Trial

Among 60 patients with diffuse large B-cell lymphoma (DLBCL) and disease progression following prior CAR T-cell therapy, IRC assessment reported an ORR of 48%. Additionally, 32% of patients had a CR, and the median DOR among responders (n = 29) was 15 months (95% CI, 3 months-NE).3

The open-label, multicenter, phase 1 ELM-1 trial assessed the safety and tolerability of odronextamab as a treatment for those with CD20-positive B-cell malignancies who received prior anti-CD20 therapy.4

Pooled safety data from the ELM-1 and ELM-2 trials revealed that the most common adverse effects (AEs) included CRS (54%), neutropenia (41%), pyrexia (39%), anemia (38%), thrombocytopenia (27%), and diarrhea (24%). The most frequently observed serious AEs included CRS (14%), pneumonia (9%), and COVID-19 (9%).

Odronextamab previously earned EU approval in relapsed/refractory follicular lymphoma or DLBCL following at least 2 prior lines of therapy in August 2024.3

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/nhzwz4hv
2. Kim TM, Taszner M, Novelli S, et al. Safety and efficacy of odronextamab in patients with relapsed or refractory follicular lymphoma. Ann Oncol. Published online August 13, 2024. doi:10.1016/j.annonc.2024.08.2239
3. 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/yk7acc5k
4. Study to investigate the safety and tolerability of odronextamab in patients with CD20+ B-Cell malignancies (ELM-1). ClinicalTrials.gov. Updated November 5, 2024. Accessed February 26, 2025. https://tinyurl.com/2at4wsvw