Pfizer’s Elranatamab Granted FDA Breakthrough Therapy Designation for r/r Multiple Myeloma

Pfizer announced its investigational cancer immunotherapy, elranatamab, received Breakthrough Therapy Designation from the FDA for the treatment of people with relapsed or refractory multiple myeloma (RRMM).

Elranatamab is a B-cell maturation antigen (BCMA)-CD3-targeted bispecific antibody (BsAb).

The Breakthrough Therapy Designation is based on six-month follow-up data from cohort A (n=123) of MagnetisMM-3, an open-label, multicenter, single arm, Phase 2 study evaluating the safety and efficacy of elranatamab monotherapy in patients with RRMM. Patients received subcutaneous (SC) elranatamab 76 mg weekly (QW) with a 2-step-up priming dose regimen administered during the first week. The study showed elranatamab demonstrated a manageable safety profile, and at a median follow-up of 6.8 months, patients achieved an overall response rate (ORR) of 61.0%. Among responders, there was 90.4% probability of maintaining a response ≥6 months. The most common treatment-emergent adverse event (TEAE) regardless of causality was CRS (57.9%), with the majority of events reported being either Grade 1 (43.2%) or Grade 2 (14.2%). Updated data from MagnetisMM-3 will be presented at the 64th American Society of Hematology Annual Meeting and Exposition 2022 (ASH 2022), December 10-13, 2022.

MagnetisMM-3 is part of the MagnetisMM clinical research program, which has registration-intent trials planned or ongoing that explore elranatamab both as monotherapy and in combination with standard or novel therapies, spanning multiple patient populations from newly diagnosed multiple myeloma (NDMM), double-class exposed disease and RRMM.
BsAbs are a novel form of cancer immunotherapy that bind to and engage two different targets at once. One arm binds directly to specific antigens on cancer cells and the other arm binds to T-cells, bringing both cell types together. Elranatamab is designed to bind to BCMA, which is highly expressed on the surface of multiple myeloma (MM) cells, and the CD3 receptor found on the surface of T-cells, bridging them together and activating the T-cells to kill the myeloma cells. The binding affinity of elranatamab for BCMA and CD3 has been engineered to elicit potent T-cell mediated anti-myeloma activity. Elranatamab is administered subcutaneously, which offers more convenience over intravenous administration, and may mitigate the risk of potential adverse events, such as cytokine release syndrome (CRS).
In addition to the Breakthrough Therapy Designation, elranatamab has been granted Orphan Drug Designation by the FDA and the European Medicines Agency (EMA) for the treatment of MM. The FDA and EMA have granted elranatamab Fast Track Designation and the PRIME scheme, respectively, for the treatment of patients with RRMM. The UK Medicines and Healthcare Products Regulatory Agency (MHRA) has also granted elranatamab Innovative Medicine Designation and the Innovation Passport, for the treatment of MM.

Elranatamab’s launch in triple class r/r MM (refractory to immunomodulators, proteasome inhibitors, and anti-CD38 therapy) is expected in Q3/2023 in US and Q4/2023 in EU, under the assumptions of priority review granted by FDA and an accelerated assessment granted by EMA. However, due to the long P&R negotiations, it is unlikely to launch within the EU in 2023. 

It is unclear whether Pfizer will be submitting elranatamab for approval in the 4L+ or 5L+ triple-class r/r MM setting.

source: press release