On August 14, 2023, the United States Food and Drug Administration (FDA) granted accelerated approval to elranatamab-bcmm (Elrexfio, Pfizer, Inc.).
According to the FDA, elranatamab is indicated for adults with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor (such as bortezomib, carfilzomib or ixazomib), an immunomodulatory agent (such as lenalidomide, pomalidomide or thalidomide), and an anti-CD38 monoclonal antibody (such as daratumumab or isatuximab).
Elranatamab is a bispecific antibody which targets BCMA on multiple myeloma cells and CD3 at the surface of T-cells. CD3 (cluster of differentiation 3) is a protein complex involved in T-cell-mediated immune response and BCMA (B-cell maturation antigen) plays an important role for the proliferation and survival of B-cells, which are immune cells producing antibodies and protecting the body from infections. BCMA also differentiates these cells into plasma cells. It is an antigen preferentially found at the surface of myeloma cells. Elranatamab facilitates tumour cell elimination through a bispecific interaction by bringing T-cells and myeloma cells into close contact.
Bispecific antibodies are promising immunotherapies under investigation for the treatment of multiple myeloma. Different products targeting different antigens are being studied, many with preliminary results showing high rates of response. Among those, teclistamab (TECVAYLITM), which is also targeting BCMA on myeloma cells and CD3 on T-cells, has already been approved by the FDA in October 2022 and received conditional marketing authorisation in the European Union in August 2022. On August 9, 2023, talquetamab (TALVEYTM), which targets GPRC5D on myeloma cells and CD3 on T-cells, also received accelerated approval from the FDA. In the European Union, its conditional marketing authorisation is pending.
As for the use of elranatamab in the European Union, the European Medicines Agency (EMA) medicine designated it as an orphan medicine for treating myeloma on July 29, 2021. This means that Pfizer received scientific and regulatory support from the EMA to advance this medicine to the stage where they can apply for marketing authorisation. The EMA has accepted elranatamab’s marketing authorisation application in February 2023. The Committee for Medicinal Products for Human Use (CHMP), ), which is the European Medicines Agency’s (EMA) committee responsible for human medicines, will then provide an opinion on elranatamab. Finally, the European Commission will take a legally binding decision based on the EMA’s recommendation.
Elranatamab approval is based on efficacy results from the MagnetisMM-3 clinical trial, which included one group of 97 relapsed/refractory myeloma patients who had previously received at least four prior lines of therapies but no prior BCMA-directed therapy. Another group of 64 patients had had prior exposure to BCMA-directed therapy. Patients received subcutaneous elranatamab weekly on a 28-day cycle with a step-up priming dose regimen. Step-up doses in the first week of therapy are meant to incrementally increase the dose administered before reaching the target dose level to prime the immune system gradually and reduce side-effects. For patients receiving six or more cycles and achieving a partial response or better for at least two months, the dosing interval was then reduced to once every two weeks.
The MagnetisMM-3 clinical trial assessed response rates to elranatamab and duration of response. 58% of the patients who received elranatamab as their first BCMA-directed therapy responded to the treatment, and 82% of those maintained their response for at least nine months. 33% of the patients who had prior exposure to BCMA-directed therapy responded to the treatment, and 84% of those maintained their response for at least nine months. Results show that switching to biweekly dosing may improve long-term safety without compromising efficacy.
The most common adverse reactions observed with elranatamab treatment include cytokine release syndrome (CRS), fatigue, injection site reaction, diarrhoea, upper respiratory tract infection, musculoskeletal pain, pneumonia, decreased appetite, rash, cough, nausea and fever.
Elranatamab is currently under investigation for treating myeloma at earlier lines of therapy as monotherapy and in combination with other compounds.