Once-monthly Elrexfio sets new standard for multiple myeloma

Extends dosing interval for patients maintaining a response

Expected to improve treatment continuity and ease management burden

Elrexfio, a treatment for relapsed or refractory multiple myeloma (RRMM), is emerging as a new option in the hematologic cancer landscape where long-term treatment is inevitable, by extending its dosing interval. This measure is evaluated as a strategic move that simultaneously considers treatment continuity and patient convenience for those who have maintained a response for a certain period.

Pfizer’s Elrexfio

According to industry sources on the 15th, Pfizer’s RRMM treatment 'Elrexfio (elranatamab)' recently extended its dosing interval from once every two weeks to once every four weeks.

The Ministry of Food and Drug Safety revised the product label last October to permit once-every-four-weeks dosing, only for patients who achieved a response after at least 24 weeks of treatment and subsequently maintained that response with dosing at 2-week intervals for 24 weeks or longer.

This change is significant not merely as a schedule adjustment but because it provides a sustainable treatment environment for multiple myeloma patients requiring long-term care. With the extended interval, patients can reduce their hospital visits by half, easing the physical and psychological burden accumulated during long-term treatment.

Multiple myeloma is a representative hematologic cancer characterized by the abnormal proliferation of plasma cells in the bone marrow. Due to its inherent nature of recurrent relapse and resistance, long-term management is considered the cornerstone of treatment. In Korea, the number of patients is steadily increasing due to an aging population and advancements in diagnostic technology, with approximately 2,000 new cases reported annually as of 2022. Its age of onset is concentrated in the elderly population aged 60 and above, posing significant challenges for treatment continuity.

While the treatment landscape for multiple myeloma has rapidly advanced with the introduction of various options such as proteasome inhibitors (PI), immunomodulatory drugs (IMiD), and anti-CD38 monoclonal antibodies, a significant limitation remains as a substantial number of patients eventually develop resistance to existing therapies or experience relapse. This has heightened the demand for new treatment strategies that can overcome drug resistance while maintaining long-term response.

Elrexfio subcutaneous injection formulation offers a short administration time and greater convenience for both healthcare providers and patients compared to intravenous injections. This approval for once-every-four-weeks dosing maximizes these formulation advantages and represents an opportunity to strengthen the paradigm of patient-centered care.

As a BCMA-targeted bispecific antibody, Elrexfio features a mechanism where one antibody simultaneously recognizes CD3 on T-cells and BCMA on tumor cells. By directly linking these two cells, it induces T-cells to selectively attack cancer cells. The formation of this immune synapse triggers T-cell activation and cytotoxic responses, promoting tumor cell death.

Contrary to chimeric antigen receptor T-cell (CAR-T) therapies that require complex cell collection and manufacturing processes, Elrexfio can be administered immediately via subcutaneous injection and stably expresses both target specificity and immune activation. It is administered at a fixed dose regardless of body weight, and a stepwise dose escalation and pre-treatment protocol is applied to minimize the risk of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS).

Clinical evidence also supported the extended dosing interval. Long-term follow-up results from the global Phase II MagnetisMM-3 study showed an objective response rate (ORR) of 61.0% and a complete response (CR) or better rate of 37.4% in 123 patients with relapsed or refractory multiple myeloma who had failed triple therapy. The median progression-free survival (PFS) was 17.2 months, and the median overall survival (OS) was 24.6 months.

Consistent efficacy was also confirmed in real-world data. The COTA study, which compared the MagnetisMM-3 clinical results to the real-world setting, found that the Elrexfio group showed a 43% lower risk of progression-free survival and a 47% reduction in the risk of death compared to the physician's choice of therapy. The most commonly used physician's choice of therapy in COTA was DPd (daratumumab-pomalidomide-dexamethasone), KPd (carfilzomib-pomalidomide-dexamethasone), and Kd-cyclophosphamide.

A matched cohort analysis using the US Flatiron Health (FH) database also showed a 59% reduction in the risk of progression-free survival and a 40% reduction in the risk of death. The most frequently used treatment regimens in the FH cohort were Kd (carfilzomib-dexamethasone), DPd, and EPd (elotuzumab-pomalidomide-dexamethasone).

Based on this clinical and real-world evidence, the U.S. Food and Drug Administration (FDA) and the Ministry of Food and Drug Safety (MFDS) officially approved Elrexfio’s once-every-four-weeks dosing regimen. As the focus of multiple myeloma treatment shifts from short-term response to how long and stable treatment can be sustained, Elrexfio’s dosing strategy could likely become a major turning point.

Professor Ki-hyun Kim of the Hematology-Oncology Department at Samsung Medical Center stated, "Elrexfio’s bispecific antibody platform enhances both treatment accessibility and effectiveness by directly utilizing the patient’s T-cells without separate cell manipulation. This transition to once-monthly dosing is a meaningful step forward in alleviating the burden of long-term treatment and helping patients regain their daily lives."