Elrexfio approved for hard-to-treat multiple myeloma patients in Europe
Indicated in EU, US for adults with cancer's advance after last of 3 therapy lines
The European Commission has granted conditional marketing authorization to Elrexfio (elranatamab) to treat adults with multiple myeloma who received at least prior three lines of therapy and whose cancer has worsened since their last therapy.
The indication covers patients on all 27 countries of the European Union, as well as in Iceland, Liechtenstein, and Norway. Previous therapy lines need to include at least one proteasome inhibitor, an immunomodulatory agent, and a CD38 inhibitor.
Approval comes on the heels of positive feedback from a European Medicines Agency committee recommending that Pfizer’s Elrexfio — an off-the-shelf, or ready-to-use, therapy given as a subcutaneous (under the skin) injection at a fixed dose — be used on its own for hard-to-treat multiple myeloma, according to a company press release.
New treatment option for people with relapsed and refractory multiple myeloma
Conditional marketing authorization is granted to medications that address unmet needs based on less comprehensive clinical data than normally is required. Standard approval will depend on the submission of additional findings in the ongoing Phase 2 MagnetisMM-3 clinical trial (NCT04649359), as well as results from a Phase 3 trial potentially confirming the therapy’s clinical benefit.
Elrexfio was conditionally approved in the U.S. in August for adults with relapsed and refractory multiple myeloma who received at least four prior lines of therapy. Full approval also is dependent on Phase 3 trial data confirming the medication’s benefits.
According to Pfizer, Elrexfio also is available in Switzerland and Brazil.
“More than 50,000 Europeans are diagnosed with multiple myeloma each year, and too often, they face relapse and treatment resistance,” said Chris Boshoff, MD, PhD, Pfizer’s chief oncology research and development officer and executive vice president.
“Today’s approval provides a new, broadly available option for people with hard-to-treat multiple myeloma, and we continue to explore the use of Elrexfio in earlier lines of treatment so that more people may ultimately benefit from this therapy,” Boshoff added.
Multiple myeloma is a rare cancer of the plasma cells — a type of white blood cell that produces antibodies — in which they grow out of control, resulting in abnormal, immature plasma cells filling up the bone marrow. When these cells become cancerous, they produce abnormal proteins that can cause a wide range of disease symptoms.
Despite the many approved myeloma treatments, patients often fail to respond to available medications or relapse after treatment.
Elrexfio contains an antibody that targets both B-cell maturation antigen (BCMA), a protein found at high levels on the surface of myeloma cells, and CD3, a cell surface protein present on immune T-cells. By bringing T-cells close to myeloma cells, the therapy is expected to promote the elimination of myeloma cells.
Elrexfio’s conditional approval supported by Phase 2 trial data
The European Commission’s decision was based on data from 123 adults with relapsed or refractory multiple myeloma who took part in the MagnetisMM-3 study. All had failed to respond to at least three therapy lines, none targeting BCMA.
After two step-up priming doses, all received 76 mg injections of Elrexfio once weekly in four-week cycles for about six months. Those who achieved a partial response or better were allow to switch to every-other-week dosing.
Results showed that 61% of patients had a partial or complete response to Elrexfio, with 71.5% being likely to maintain their response, meaning no cancer worsening, for 15 months.
Among the 50 patients who switched to every-other-week dosing, 40 (80%) maintained or improved their response for at least six months after the switch, with 38% reaching a complete response or better.
The most common side effects reported with Elrexfio included cytokine release syndrome (CRS; 58%), a sudden, heightened inflammatory response that can cause fever, a rapid heartbeat, low blood pressure, and trouble breathing. This was followed by low red blood cell counts (54%), low numbers of immune cells called neutrophils (45%), and fatigue (44%).
The therapy also is associated with an increased risk for immune effector cell-associated neurotoxicity syndrome (ICANS), a serious form of brain inflammation that can cause neurological symptoms such as confusion, mood swings, seizures, an altered level of consciousness, and brain swelling.
Due to the risk of CRS and ICANS, patients should be monitored for 48 hours after the two step-up doses.
Pfizer’s MagnetisMM clinical program is exploring the potential of Elrexfio, either alone or as part of a combination therapy, at various stages of disease progression, including as an earlier line of treatment.
The ongoing Phase 3 MagnetisMM-5 trial (NCT05020236) is testing Elrexfio, alone or in combination with Darzalex (daratumumab), against the standard treatment combination of Darzalex, Pomalyst (pomalidomide), and dexamethasone in up to 854 multiple myeloma patients.
All participants must have previously failed to adequately respond to Revlimid (lenalidomide) and a proteasome inhibitor, but not more than three lines of therapy. Recruitment for this study may still be open at multiple sites around the world.
Elrexfio is also being tested as a combination therapy in the Phase 3 MagnetisMM-6 trial (NCT05623020) in newly diagnosed patients who are not eligible for a stem cell transplant, and in the Phase 3 MagnetisMM-7 study (NCT05317416) in newly diagnosed patients after that transplant, where it is being given as a monotherapy.
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