P-BIO
October 13, 2023
ELREXFIO is an off-the-shelf (ready-to-use) BCMA-directed immunotherapy that induces deep and durable responses with a manageable tolerability profile, as well as convenient subcutaneous dosing
Pfizer today announced the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion, recommending marketing authorization for ELREXFIO™ (elranatamab). ELREFXIO is a targeted immunotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma (RRMM) who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody and have demonstrated disease progression on the last therapy. ELREXFIO was evaluated through the EMA PRIME scheme, a program that supports the development of medicines that target an unmet medical need, and through Orphan Drug Designation. The European Commission (EC), which authorizes central marketing approvals in the European Union (EU), will take a legally binding decision based on the CHMP recommendation and is expected to make a final decision in the coming months. If granted, the decision will apply to all 27 EU member states plus Iceland, Liechtenstein, and Norway.
“People with multiple myeloma are prone to relapse and resistance, and they often have no choice but to recycle treatment classes as they go through successive rounds of therapy. Efficacious and tolerable new treatments are desperately needed, especially in later-line care,” said MagnetisMM clinical trial investigator Mohamad Mohty, M.D., Ph.D., Professor of Hematology and Head of the Hematology and Cellular Therapy Department at the Saint-Antoine Hospital and Sorbonne University, Paris, France. “With its generally manageable safety profile and clinically meaningful and durable responses among hard-to-treat patients, ELREXFIO offers a new tool in the fight against relapse and resistance.”
ELREXFIO is a subcutaneously delivered B-cell maturation antigen (BCMA)-CD3-directed bispecific antibody (BsAb) immunotherapy that binds to BCMA on myeloma cells and CD3 on T-cells, bringing them together and activating the T-cells to kill myeloma cells. The CHMP recommendation is based on data from cohort A of the Phase 2 MagnetisMM-3 study (NCT04649359) showing meaningful responses among heavily pretreated RRMM patients (at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody) who received ELREXFIO as their first BCMA-directed therapy. In an analysis of these patients (n=123) at 15 months, the objective response rate was 61%, with a 72% probability of maintaining a response at 15 months. These data were recently published in Nature Medicine.
The results from MagnetisMM-3 also established once-every-other-week dosing with ELREXFIO for responding patients after 24 weeks of weekly therapy, which means less time at the clinic and potentially greater long-term treatment tolerability. Among responding patients who switched to every-other-week dosing at least six months prior to the data cut-off date (n=50), 80% maintained or improved their response after the switch, with 38% attaining a complete response (CR) or better after the switch.
“We discovered and developed ELREXFIO as an off-the-shelf (ready-to-use) fixed-dose option with a subcutaneous administration to be broadly accessible as quickly as possible,” said Chris Boshoff, Chief Oncology Research and Development Officer and Executive Vice President, Pfizer. “We’re excited at the possibility of ELREXFIO reaching people with multiple myeloma that have relapsed and refractory disease across Europe. We’re also exploring the use of ELREXFIO in earlier lines of therapy to potentially help even more people with multiple myeloma.”
The extensive MagnetisMM clinical development program is investigating ELREXFIO’s use across the entire spectrum of patients with multiple myeloma, from those with newly diagnosed multiple myeloma to RRMM. Ongoing registrational-intent trials are exploring ELREXFIO both as monotherapy and in combination with standard or novel therapies. These include MagnetisMM-5 in the double-class exposed setting, MagnetisMM-6 in newly diagnosed patients who are ineligible for stem cell transplant, and MagnetisMM-7 in newly diagnosed patients after transplant.
The most common adverse reactions to ELREXFIO are cytokine release syndrome (CRS) (58%), anemia (54%), neutropenia (45%), fatigue (44%), upper respiratory tract infection (39%), injection site reaction (38%), diarrhoea (38%), pneumonia (37%), thrombocytopenia (36%), lymphopenia (30%), decreased appetite (27%), rash (26%), joint pain (arthralgia) (25%), fever (pyrexia) (27%), hypokalemia (23%), nausea (21%), and dry skin (21%). Serious adverse reactions are pneumonia (31%), sepsis (15%), CRS (13%), anemia (6%), upper respiratory tract infection (5%), urinary tract infection (3%), febrile neutropenia (3%), dyspnea (2%), and pyrexia (2%).
ELREXFIO received approval from the U.S. Food and Drug Administration (FDA) in August 2023 under the FDA’s Accelerated Approval Program, which allows for earlier approval of drugs that treat serious conditions and fill an unmet medical need. The FDA review was also conducted under Project Orbis, a framework for the concurrent submission and review of oncology drugs among international partners to potentially expedite approvals. ELREXFIO has been approved under Project Orbis in Switzerland, and four other countries (Brazil, Canada, Australia, and Singapore) are participating. The UK Medicines and Healthcare Products Regulatory Agency (MHRA) has granted ELREXFIO Innovative Medicine Designation and the Innovation Passport, for the treatment of MM.
Read the full press release here.
