FDA Approves Motixafortide Plus Filgrastim for ASCT in Multiple Myeloma

FDA

The FDA has approved motixafortide (Aphexda) in combination with filgrastim (Neupogen) to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous stem cell transplant (ASCT) in patients with multiple myeloma.

The approval was supported by data from the phase 3 GENESIS trial (NCT03246529), which showed that 67.5% of patients treated a single administration of motixafortide plus filgrastim achieved a collection of at least 6 × 10⁶ CD34+ cells/kg in up to 2 apheresis sessions compared with 9.5% of patients treated with placebo plus filgrastim, per central laboratory assessment (P < .0001). Per local assessment, those rates were 92.5% and 21.4% for the motixafortide and placebo arms, respectively.

"Greater numbers of patients with multiple myeloma are candidates for autologous stem cell therapy; however, achieving target collection goals can be difficult in some patients given modern barriers, including the treatment of older patients and use of contemporary induction regimens," John DiPersio, MD, PhD, primary investigator for the GENESIS trial and professor of medicine, pathology and immunology and director of the Center for Gene and Cellular Immunotherapy at Washington University School of Medicine in St. Louis, stated in a news release.

"Innovation in this area of medicine has been needed, and today's approval of [motixafortide] addresses the demand for new therapies that can meet today's challenges by delivering more reliability in stem cell mobilization, vs filgrastim alone, with fewer days of apheresis sessions and fewer doses of filgrastim for people living with this cancer."

The randomized, double-blind, placebo-controlled GENESIS study evaluated the safety and efficacy of motixafortide plus filgrastim compared with placebo plus filgrastim for the mobilization of hematopoietic stem cells for ASCT in patients between 18 and 78 years of age with histologically confirmed multiple myeloma.² Patients needed to be at least 1 week removed from their last induction cycle of cytoreductive chemotherapy, and no single agent chemotherapy/maintenance was allowed within 7 days. Patients also were required to be eligible for ASCT per investigator discretion and be in first or second complete remission or partial remission. An ECOG performance status of 0 or 1 and adequate organ function at screening were also required.

Prior ASCT or allogeneic stem cell transplant, or failed prior attempts to collect hematopoietic stem cells excluded patients from the study.

Part 1 was a single-center, lead-in, open-label study featuring 12 patients who received motixafortide plus filgrastim designed to determine the recommended dose.¹

Part 2 included 122 patients who were randomly assigned 2:1 to 1.25 mg/kg of motixafortide plus filgrastim or placebo plus filgrastim.^1,2

The primary end point of the study was the rate of patients who experienced the mobilization of at least 6 × 10⁶ CD34+ cells in up to 2 apheresis sessions. Evaluating if 1 dose of motixafortide plus filgrastim was superior to placebo plus filgrastim in the ability to mobilize at least 6 × 10⁶ CD34+ cells in 1 apheresis session was a key secondary end point.¹

Regarding safety, serious adverse effects (AEs) were reported in 5.4% of patients treated with 1.25 mg/kg of motixafortide plus filgrastim (n = 92). Serious AEs included vomiting, injection-site reaction, hypersensitivity reaction, injection site cellulitis, hypokalemia, and hypoxia. The most common AEs reported in more than 20% of patients consisted of injection-site reactions, pruritus, flushing, and back pain.

References

1. BioLineRx announces FDA approval of Aphexda (motixafortide) in combination with filgrastim (G-CSF) to mobilize hematopoietic stem cells for collection and subsequent autologous transplantation in patients with multiple myeloma. News release. BioLineRx. September 11, 2023. Accessed September 11, 2023. https://ir.biolinerx.com/news-releases/news-release-details/biolinerx-announces-fda-approval-aphexdatm-motixafortide
2. A phase III, safety, tolerability and efficacy of combination treatment of BL-8040 and G-GSF as compared to placebo and G-CSF for the mobilization of hematopoietic stem cells for autologous transplantation in subjects with MM (GENESIS). ClinicalTrials.gov. Updated June 16, 2022. Accessed September 11, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT03246529