Ordspono (odronextamab) approved in the European Union for the treatment of relapsed/refractory follicular lymphoma and diffuse large B-cell lymphoma – Regeneron Pharma

Regeneron Pharmaceuticals, Inc. announced that the European Commission (EC) has approved Ordspono (odronextamab) to treat adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) or R/R diffuse large B-cell lymphoma (DLBCL), after two or more lines of systemic therapy. This marks the first regulatory approval of Ordspono in the world for these patients. Ordspono is a bispecific antibody that acts by linking the lymphoma cell to a killer T cell.

“The EC approval of Ordspono is a meaningful advancement for EU patients and their physicians as a new option to treat both indolent and aggressive lymphomas,” said Stefano Luminari, M.D., Professor of Oncology at the University of Modena and Reggio Emilia, hematologist at the Hematology Unit of Arcispedale Santa Maria Nuova in Reggio Emilia, and a trial investigator. “In clinical trials, Ordspono demonstrated remarkable complete response rates in follicular lymphoma, as well as compelling efficacy results in diffuse large B-cell lymphoma, including in the post-CAR-T setting. Physicians, especially in the community setting, will have an off-the-shelf option that can be administered out-patient – offering the chance for complete remission.”

The approval is based on results from the Phase 1 ELM-1 and pivotal Phase II ELM-2 trials, which demonstrated robust, durable response rates in adults with R/R FL or R/R DLBCL: In R/R FL:, results from ELM-2 (N=128) as assessed by an independent review committee (IRC) showed an objective response rate (ORR) of 80%, with 73% achieving a complete response (CR). Among complete responders, the median duration of response (DoR) was 25 months (95% confidence interval [CI]: 20 months to not estimable [NE]). In R/R DLBCL : results from ELM-2 (N=127) in patients who were CAR-T therapy naive, as assessed by an IRC showed 52% ORR, with 31% achieving a CR. Among complete responders the median DoR was 18 months (95% CI: 10 months to NE).results from ELM-1 (N=60) in patients who had progressed after CAR-T therapy, as assessed by an IRC showed 48% ORR, with 32% achieving a CR. Among responders (n=29), the median DoR was 15 months (95% CI: 3 months to NE).

The most common adverse reactions were cytokine release syndrome (CRS; 54%), neutropenia (41%), pyrexia (39%), anemia (38%), thrombocytopenia (27%), diarrhea (24%) and COVID-19 (22%). The most common serious adverse reactions were CRS (14%), pneumonia (9%), COVID-19 (9%) and pyrexia (6%). Ordspono can cause serious or fatal infections, and CRS, which may be serious or life-threatening.

“Ordspono marks the first approval from our bispecific antibody platform, which we hope will increasingly contribute to our growing portfolio of practice-changing medicines for oncology and other diseases,” said George D. Yancopoulos, M.D., Ph.D., Board co-Chair, President and Chief Scientific Officer of Regeneron. “Building upon this approval, we are excited about our OLYMPIA program, which includes multiple Phase III trials investigating Ordspono as a monotherapy and in various combinations, in earlier lines of therapy. We’re also excited to be advancing our broader pipeline of CD3 and other bispecific therapies, both to additional hematologic cancers such as myeloma, as well as to solid tumors.”

About the Ordspono (odronextamab) Clinical Trial Program : Ordspono is a CD20xCD3 bispecific antibody designed to bridge CD20 on cancer cells with CD3-expressing T cells to facilitate local T-cell activation and cancer-cell killing. Ordspono as monotherapy is indicated for the treatment of adult patients with R/R FL or R/R DLBCL, after two or more lines of systemic therapy. ELM-1 is an ongoing, open-label, multicenter Phase 1 trial to investigate the safety and tolerability of odronextamab in patients with CD20+ B-cell malignancies previously treated with CD20-directed antibody therapy, including a cohort of patients who had progressed after CAR-T therapy. ELM-2 is an ongoing, open-label, multicenter Phase II trial investigating odronextamab across five independent disease-specific cohorts, including DLBCL, FL, mantle cell lymphoma, marginal zone lymphoma and other subtypes of B-NHL. The primary endpoint is ORR according to the Lugano Classification as assessed by IRC, and secondary endpoints include CR, progression-free survival, overall survival and DoR.

Regeneron is conducting a broad Phase III development program, known as OLYMPIA, investigating odronextamab in earlier lines of therapy and other B-NHLs. In addition, Regeneron is investigating odronextamab in combination with a costimulatory bispecific antibody, REGN5837 (CD22xCD28), and Regeneron’s PD-1 inhibitor cemiplimab for R/R aggressive B-NHL through the ATHENA-1 and CLIO-1 studies, respectively. These potential uses are investigational, and their safety and efficacy have not been evaluated by any regulatory authority. For more information, visit the Regeneron clinical trials website, or contact via clinicaltrials@regeneron.com or +1 844-734-6643.