Elranatamab under FDA priority review for hard-to-treat myeloma
A response to the application is anticipated this year
The U.S. Food and Drug Administration (FDA) has granted priority review to Pfizer‘s application of its investigational under-the-skin therapy elranatamab for people with relapsed or refractory multiple myeloma.
Priority review is given to therapies that target serious medical conditions that outperform current treatments to make them available to patients faster. The status is expected to shorten the regulatory review process to six months from the standard 10 months, meaning a response from the FDA is anticipated this year. A similar application was accepted by the European Medicines Agency (EMA).
“We believe that elranatamab, if approved, has the potential to become the next standard of care for multiple myeloma given its favorable clinical results and convenient [under-the-skin] route of administration,” said Chris Boshoff, MD, PhD, chief development officer at Pfizer, in a company press release. “We look forward to working with the FDA and EMA to bring this new innovative medicine to patients globally.”
Elranatamab has received orphan drug status in the U.S. and Europe for multiple myeloma. It was also granted the FDA’s breakthrough therapy and fast-track designations, and the EMA’s PRIME designation for relapsed or refractory multiple myeloma.
The designations are meant to accelerate a therapy’s clinical development and regulatory review, providing financial incentives, more regulatory support, and marketing exclusivity periods upon approval.
The FDA also accepted elranatamab for Project ORBIS, a framework for the concurrent submission and review of anti-cancer treatments to accelerate approvals in some countries outside the US. So far, Switzerland, Brazil, Canada, Australia, and Singapore have agreed to participate.
It also received an Innovative Medicine Designation and Innovation Passport in the U.K. for multiple myeloma, a type of cancer affecting plasma cells, a type of white blood cell that normally produces antibodies to fight infections. Despite advances in treatment options, multiple myeloma is still “a fatal [blood related] malignancy, with a median survival of just over five years,” Boshoff said.
Elranatamab is an off-the-shelf antibody-based therapy designed to engage with two different targets at once — BCMA, a protein highly present on the surface of myeloma cells, and the CD3 receptor, on the surface of immune T-cells. Administered via under-the-skin injections, it’s expected to bring these two cell types together, activating the T-cells to kill the myeloma cells.
“As an off-the-shelf treatment, BCMA bispecific antibodies are heralding a new treatment paradigm that can greatly impact the lives of people with this disease,” Boshoff added.
Both approval applications are primarily supported by data of 123 adults with relapsed and refractory disease who received elranatamab as part of the first patient group in the ongoing Phase 2 MagnetisMM-3 trial (NCT04649359).
Results of MagnetisMM trial
The patients failed to respond to at least three prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody, but hadn’t received any BCMA-targeting treatment.
Participants received a weekly elranatamab dose of 76 mg on a 28-day cycle, with a step-up priming dose regimen, wherein a 12 mg dose was given on day 1 and a 32 mg dose was given on day 4 during the first cycle. Dosing was once every two weeks for those receiving six or more cycles who achieved a partial response or better for at least two months.
The study’s primary goal is to assess the response rate, assessed about once a month up to about two years.
At a median follow-up of 10.4 months, 61% of patients responded to elranatamab, with 55% achieving a very good partial response or better. There was an 84% probability of maintaining a treatment response at nine months as well as a 63% probability of no evidence of disease progression, and a 70% chance of being alive at nine months.
Data also suggested elranatamab has a manageable safety profile. The two step-up priming dose regimen, given to 119 patients, helped mitigate the rate and severity of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), according to the company. CRS is a potentially life-threatening immunotherapy complication. ICANS is an inflammation-associated neurological disorder.
Mild or moderate CRS occurred in 43% of patients after the first dose, 24% after the second dose, 6% after the third, and 1% after dose four. ICANS cases (3%) were neither common nor severe, with only mild to moderate cases reported.
About the MagnetisMM research program
MagnetisMM-3 is part of the MagnetisMM clinical research program exploring elranatamab, alone or in combination with other therapies, across patient populations, from newly diagnosed to relapsed and refractory myeloma.
The ongoing Phase 3 MagnetisMM-5 trial (NCT05020236) is testing elranatamab alone and/or in combination with Darzalex (daratumumab) against the combination of Darzalex, Pomalyst (pomalidomide), and dexamethasone. It’s recruiting up to 589 adult patients previously treated with Revlimid (lenalidomide) and a proteasome inhibitor.
A second Phase 3 trial, MagnetisMM-6 (NCT05623020), is testing elranatamab, Darzalex, and Revlimid combined against Darzalex, Revlimid, and dexamethasone.
The trial is enrolling up to 646 adults who received up to two prior lines of therapy, including at least one immunomodulatory and one proteasome inhibitor, or newly diagnosed patients ineligible for a stem cell transplant.
A third Phase 3 study, called MagnetisMM-7 (NCT05317416), is enrolling up to 700 adult patients to evaluate elranatamab alone as a maintenance treatment after a stem cell transplant in newly diagnosed patients.
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