Linvoseltamab Earns FDA Priority Review in Relapsed/Refractory Multiple Myeloma

The regulatory agency has set a Prescription Drug User Fee Act date of August 22, 2024, for its decision on approving linvoseltamab in relapsed/refractory multiple myeloma.

The FDA has granted priority review to a biologics license application (BLA) for linvoseltamab as a treatment for adult patients with relapsed/refractory multiple myeloma who have previously received 3 or more lines of therapy, according to a press release from Regeneron Pharmaceuticals, Inc.¹

The regulatory agency has set a Prescription Drug User Fee Act date of August 22, 2024, for its decision on approving linvoseltamab in the indication above.

Supporting data for the BLA came from the phase 1/2 LINKER-MM1 trial (NCT03761108) evaluating linvoseltamab in relapsed/refractory multiple myeloma. After a median follow-up of 11 months, the agent elicited an objective response rate (ORR) of 71% based on independent review committee assessment among 117 evaluable patients; complete responses (CRs) or better were reported in 46% of the cohort.² Additionally, those who achieved a very good partial response (VGPR) or better following 24 or more weeks of treatment were eligible to switch from biweekly dosing to receiving the agent every 4 weeks.

Any-grade adverse effects (AEs) occurred in 100% of patients of who received linvoseltamab at 200 mg, and grade 3 or higher toxicities affected 85%. Cytokine release syndrome (CRS) occurred in 46% of patients, with 35% experiencing grade 1 instances, 10% having grade 2 toxicity, and 1% experiencing grade 3 CRS. Any-grade adjudicated immune effector cell-associated neurotoxicity syndrome (ICANS) was highlighted in 8% of patients; grade 3 ICANS affected 3 patients.

Any-grade infections were highlighted in 73% of patients, with 34% experiencing grade 3/4 events. Additionally, 12% of patients died due to treatment-emergent AEs on study treatment or within 30 days following their last dose, 9% of whom died due to infections.

“With longer follow-up data on linvoseltamab, we’re seeing deep and durable responses with a [CR] rate nearing 50% in a difficult-to-treat patient population who had received a median of 5 prior lines of therapy,” L. Andres Sirulnik, MD, PhD, senior vice president of Translational and Clinical Sciences, Hematology at Regeneron, said in a press release on these data.² “Furthermore, in our trial, the regimen had a short monitoring time and a convenient, response-adapted administration schedule that enabled deep responders to go from every 2-week to every 4-week dosing. This regimen saved time for clinicians and patients, underscoring the potential for linvoseltamab as a patient-centric option in relapsed/refractory multiple myeloma.”

Investigators of the ongoing, multi-center LINKER-MM1 trial are evaluating linvoseltamab among 282 patients with relapsed/refractory multiple myeloma. The phase 1 portion primarily investigated the agent’s safety, tolerability, and dose-limiting toxicities across 9 dosing levels. In the phase 2 portion, investigators are assessing the agent’s safety and anti-tumor activity.

The study’s primary end point in the phase 2 dose expansion portion is ORR. Secondary end points include duration of response, progression-free survival, rates of minimal residual disease negativity, and overall survival.

Linvoseltamab will also be assessed as part of the confirmatory phase 3 LINKER-MM3 trial (NCT05730036), which is currently open for enrollment. Additionally, investigators plan to assess the agent in the first-line setting as part of a phase 1/2 trial, in high-risk smoldering multiple myeloma in a phase 2 trial, and monoclonal gammopathy of undetermined significance in a phase 2 trial.

The European Medicines Agency accepted a marketing authorization application for linvoseltamab in relapsed/refractory multiple myeloma in February 2024.³ The marketing application was also supported by data from the LINKER-MM1 trial.

References

1. Linvoseltamab BLA for treatment of relapsed/refractory multiple myeloma accepted for FDA priority review. News release. Regeneron Pharmaceuticals, Inc. February 21, 2024. Accessed February 21, 2024. https://bit.ly/3SKIMqY
2. Updated linvoseltamab pivotal data demonstrated strong rates and depth of response in patients with heavily pre-treated multiple myeloma. News release. Regeneron Pharmaceuticals, Inc. December 7, 2023. Accessed February 21, 2024. http://tinyurl.com/3n7mvyk8
3. Linvoseltamab receives EMA filing acceptance for treatment of relapsed/refractory multiple myeloma. News release. Regeneron Pharmaceuticals, Inc. February 2, 2024. Accessed February 21, 2024. http://tinyurl.com/4k32t22e