High Response Rate for Regeneron’s Myeloma Bispecific Marred by Adverse Events

 Regeneron Pharmaceuticals is taking the latest clinical data on its bispecific antibody data for multiple myeloma to the FDA, with plans to submit a BLA before the end of the year. The pharma shared mixed results Thursday morning ahead of the American Society of Hematology’s annual meeting. 

Nearly half the patients in the Phase I/II LINKER-MM1 trial achieved a complete response or better for their relapsed/refractory multiple myeloma (R/R MM) after 11 months on linvoseltamab, with a 71% objective response rate. 

Despite the positive efficacy results, the study’s data on adverse events and deaths was decidedly negative. In the trial, all 117 patients treated with the 200-mg dose experienced an adverse event with 85% experiencing Grade ≥3 adverse events. The most frequently occurring AE was cytokine release syndrome (CRS)—46%. Fourteen patients, 12% of participants, died due to treatment-emergent AEs, of which 11 were due to infections. 

Patients in the trial had been heavily pre-treated, all having received at least three prior lines of therapy or were triple refractory. Regeneron’s study design utilized a step-up dosing regimen to attempt to mitigate CRS.  

“Multiple myeloma remains an incurable disease, in which patients endure cycles of relapse and remission, resulting in a critical need for innovative medicines,” L. Andres Sirulnik, Regeneron’s senior vice president of hematology, said in a statement. Sirulnik pointed to the deep durable response in a difficult-to-treat patient population as promising and a convenient regimen that moves patients from two-week to four-week dosing as a response is seen. 

Linvoseltamab is a bispecific antibody to bridge B-cell maturation antigen (BCMA) on the cancer cells with CD3-expressing T cells to activate the immune cells’ cancer-killing power. 

If approved, Regeneron’s BCMAxCD3 therapeutic won’t be the first of its kind on the market. Johnson & Johnson’s Janssen and Pfizer both have a similar medicine approved already. However, Regeneron is hopeful for that coveted “best in class” status. While yet to be compared head-to-head, overall response rates (ORR) appear to be higher for linvoseltamab. 

The ORR for Pfizer’s Elrexfio, granted accelerated approval in August 2023, was 58% for the 97 patients in the trial. A real-world study of R/R MM patients reported in September 2023 for Janssen’s Tecvayli, the first to be approved for this class in 2022, delivered 53.6% ORR.  

Regeneron’s linvoseltamab has been granted Fast Track Designation for MM by the FDA.  

https://www.biospace.com/article/regeneron-gets-71-percent-response-rate-for-myeloma-bispecific-antibody-but-100-percent-adverse-event-rate-/