Regeneron Pharmaceuticals, Inc. (REGN) announced that the European Commission has approved odronextamab, marketed as Ordspono, for treating adult patients with relapsed or refractory (R/R) follicular lymphoma or R/R diffuse large B-cell lymphoma (DLBCL) who have received at least two prior lines of systemic therapy. This approval is based on robust results from the phase I ELM-1 and pivotal phase II ELM-2 trials, demonstrating durable response rates in patients with these aggressive forms of lymphoma.
The ELM-2 trial, involving 128 patients with R/R FL, showed an impressive 80% objective response rate (ORR), with 73% achieving a complete response. In the same trial, 127 patients who were naïve to CAR-T therapy demonstrated a 52% ORR, with 31% achieving a complete response in R/R DLBLCL. In the ELM-1 trial, 60 patients who had progressed after CAR-T therapy displayed a 48% ORR, with 32% achieving a complete response.
This EU approval marks the first regulatory approval for Ordspono globally for these patient populations. Ordspono is a bispecific antibody that functions by linking lymphoma cells to killer T cells, triggering their destruction. The EU approval was largely anticipated as the European Medicines Agency’s Committee for Medicinal Products for Human Use had already recommended approval of odronextamab, and the EMA previously granted odronextamab Orphan Designation for FL and DLBCL.
Regeneron has experienced a setback with odronextamab in the United States. In March 2024, the FDA issued complete response letters (CRLs) for its Biologics License Application (BLA) for odronextamab, seeking approval for R/R FL and R/R DLBCL. The sole issue with the approval relates to the enrollment status of the confirmatory trials. It’s important to note that the CRLs did not identify any concerns regarding the drug’s clinical efficacy, safety, trial design, labeling, or manufacturing processes.
Regeneron aims to bolster its oncology franchise, which currently features Libtayo (cemiplimab-rwlc) for certain patients with advanced basal cell carcinoma, advanced cutaneous squamous cell carcinoma, and advanced non-small cell lung cancer. The company is actively investigating the potential of odronextamab as a monotherapy and in combination therapies across earlier lines of therapy for challenging-to-treat lymphomas. These investigations include the registrational ELM-1 and ELM-2 studies, the phase III OLYMPIA development program, which is one of the largest clinical programs in lymphoma evaluating odronextamab in earlier lines of therapy and additional B-NHLs, and early-stage trials exploring chemotherapy-free combinations.
Simultaneously, Regeneron is initiating a phase II study for fianlimab, an antibody targeting LAG-3, in combination with Libtayo for perioperative non-small cell lung cancer. A phase II/III study for fianlimab, in combination with Libtayo for perioperative melanoma, is also underway.
Regeneron recently received another CRL from the FDA regarding its BLA for linvoseltamab, a pipeline candidate for treating R/R multiple myeloma. The CRL cited findings from a pre-approval inspection at a third-party fill/finish manufacturer for another company’s product candidate. This setback delays the potential approval of linvoseltamab.
Regeneron has collaboration agreements with both Bayer (BAYRY) for Eylea and Sanofi (SNY) for Dupixent. These partnerships play a significant role in the company’s revenue stream. Regeneron currently holds a Zacks Rank #3 (Hold).
