FDA Approves BioLineRx Aphexda for HSC Collections and Transplantation in Multiple Myeloma

Rare Daily Staff

The U.S. Food and Drug Administration approved BioLineRx Aphexda in combination with filgrastim to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with multiple myeloma.

Multiple myeloma is an incurable blood cancer that affects some white blood cells called plasma cells, which are found in the bone marrow. When damaged, these plasma cells rapidly spread and replace normal cells in the bone marrow. The American Cancer Society in 2023 estimated that more than 35,000 people will be diagnosed with multiple myeloma, and nearly 13,000 people will die from the disease in the United States. While some people diagnosed with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, kidney problems, or infections.

Autologous stem cell transplantation (ASCT) is part of the standard treatment paradigm for a number of blood cancers, including multiple myeloma. In the United States, as many as 8,000 ASCTs are performed each year in patients with multiple myeloma. The current ASCT standard of care includes four to six cycles of induction therapy (an initial drug-combination regimen to position the patient for as deep a treatment response as possible).

To begin the stem cell mobilization process, a patient will receive a daily dose of filgrastim for four days. Daily doses of filgrastim will continue until the target collection goal is met with the addition of up to four daily doses of plerixafor as needed. For patients unable to mobilize sufficient numbers of cells for harvesting during this primary mobilization phase, rescue therapy may be carried out followed by an additional number of apheresis sessions as necessary.

GENESIS is a two-part, phase-3, randomized, double-blind, placebo-controlled, multicenter study evaluating the safety and efficacy of Aphexda plus filgrastim, compared to placebo plus filgrastim, for the mobilization of hematopoietic stem cells for autologous transplantation in multiple myeloma patients. Part 1 was a single center, lead-in, open-label study involving patients treated with Aphexda plus filgrastim designed to ascertain the dose. Part 2 involved 122 patients who were randomized 2:1 in a double-blind, placebo-controlled, multicenter study.

The primary objective of the study was to evaluate if one dose of Aphexda plus filgrastim is superior to placebo plus filgrastim in the ability to mobilize ≥ 6 million CD34+ cells in up to two apheresis sessions. A key secondary objective of the study was to evaluate if one dose of Aphexda plus filgrastim is superior to placebo plus filgrastim in the ability to mobilize ≥ 6 million CD34+ cells in one apheresis session.

The study met the primary endpoint with a high degree of statistical significance. The assessment of CD34+ cells was performed by central and local laboratories. Central laboratory assessments were used for the efficacy results. Local laboratory results were used for clinical treatment decisions. Aphexda plus filgrastim enabled 67.5 percent of patients to achieve the cell collection goal of ≥ 6 × 106 CD34+ cells/kg in up to two apheresis sessions with a single administration, versus 9.5 percent for the placebo plus filgrastim regimen, as measured by central laboratory.

Additionally, 92.5 percent of patients reached the stem cell collection goal in up to two apheresis sessions in the Aphexda arm and 21.4 percent in the placebo arm, as measured by local laboratories. Local laboratory data were used for a sensitivity analysis. The data are descriptive and were not statistically powered nor prespecified. The information should be cautiously interpreted.

Serious adverse reactions occurred in 5.4 percent of patients receiving Aphexda plus filgrastim. Serious adverse reactions included vomiting, injection site reaction, hypersensitivity reaction, injection site cellulitis, hypokalemia and hypoxia. The most common adverse reactions occurring in GENESIS (incidence >20%) were injection site reactions (pain, erythema, and pruritus), pruritus, flushing and back pain.

BioLineRx expects to make Aphexda available later this month.

“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,” said John DiPersio, primary investigator for the GENESIS trial and director of the Center for Gene and Cellular Immunotherapy at Washington University School of Medicine in St. Louis. “Innovation in this area of medicine has been needed, and today’s approval of Aphexda addresses the demand for new therapies that can meet today’s challenges by delivering more reliability in stem cell mobilization, versus filgrastim alone, with fewer days of apheresis sessions and fewer doses of filgrastim for people living with this cancer.”