FDA Reviewing Motixafortide, Now Aphexda, for Stem Cell Transplants

Nearly 90 percent of patients collected optimal transplant cell number after one round of Aphexda

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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The U.S. Food and Drug Administration (FDA) will review BioLineRx’s application to approve Aphexda, formerly known as motixafortide, as an add-on stem cell mobilization therapy to improve stem cell transplants in people with multiple myeloma.

The decision comes about two months after the company submitted a new drug application (NDA) following a pre-NDA meeting earlier this year. In that meeting, the FDA agreed that data from the GENESIS Phase 3 clinical trial (NCT03246529), which met all its main and secondary goals, supported the application.

The agency has set a Prescription Drug User Fee Act action date for Sept. 9, 2023 meaning a decision is due by then.

“Aphexda has the potential to significantly improve outcomes and treatment experiences for patients with multiple myeloma, and the acceptance of our NDA brings us closer to this important goal,” Philip Serlin, CEO of BioLineRx, said in a company press release. “The Company is actively engaged in launch preparedness and excited about the potential of bringing this important therapeutic candidate to patients. ”

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Autologous hematopoietic stem cell transplant (AHSCT) is a standard treatment for eligible myeloma patients. It involves collecting a patient’s own healthy blood stem cells, eliminating all blood cells, and transplanting the stem cells back so their body can create new and healthy blood cells.

Currently, a compound called granulocyte colony-stimulating factor (G-CSF) is used to force blood stem cells to move from the bone marrow, where they’re produced, to the bloodstream, where they can be collected using a process called apheresis.

During this procedure a machine draws blood from the patient, and separates different types of blood cells. Only the stem cells are collected while the remaining cells are infused back into the patient.

The mobilization of blood stem cells using G-CSF alone is a slow procedure, usually requiring four to eight daily injections and one to four apheresis sessions.

Aphexda is a stem cell mobilizing therapy that works by blocking the CXCR4 receptor protein, which is involved in retaining stem cells within the bone marrow, facilitating their exit into the bloodstream.

Previous data from a Phase 2 trial (NCT02639559) showed a single injection of Aphexda was enough to mobilize as many stem cells into circulation as four to six G-CSF injections.

Aphexda has the potential to significantly improve outcomes and treatment experiences for patients with multiple myeloma, and the acceptance of our NDA brings us closer to this important goal.

Prior studies also showed Aphexda can draw cancer cells into circulation where they are more vulnerable to anti-cancer treatments and directly promote their death by activating cellular self-destruction mechanisms.

Top-line data showed Aphexda effectiveness

The NDA was mainly supported by positive top-line data from the ongoing GENESIS Phase 3 trial. The study, initiated in 2017 and which completed enrollment in 2020, is assessing the safety and effectiveness of combining Aphexda with G-CSF, as compared with G-CSF plus a placebo, at mobilizing blood stem cells for AHSCT.

Its primary objective was to evaluate whether a single Aphexda dose with G-CSF was superior to G-CSF alone at mobilizing more than six million blood stem cells in no more than two apheresis sessions. A key secondary goal was to determine whether this superiority was observed with only one apheresis session.

Other secondary objectives include the time it took for the numbers of neutrophils and platelets — two types of blood cells — to go back up, suggesting transplanted blood stem cells have started to produce blood cells (a process called engraftment), and how long engraftment lasts. Other safety and efficacy measures are also being evaluated.

Top-line data from the trial’s 122 participants confirmed earlier positive results of the superior effectiveness of the Aphexda-G-CSF combo as a stem cell mobilizing therapy.

A significantly greater proportion of patients given Aphexda and G-CSF achieved the trial’s main goal of target mobilization in up to two apheresis sessions compared with those who received G-CSF alone (70% vs. 14.3%). This represented a nearly 13 times higher likelihood of meeting the main goal with the Aphexda addition.

Similar results were obtained with only one apheresis session (67.5% vs 4.8%), with patients in the Aphexda group having a significantly greater chance (by 56 times) of reaching the target mobilization goal.

The median number of blood stem cells collected on the first day of apheresis was nearly six times higher in patients given both Aphexda and G-CSF than those in the G-CSF group (8.5 vs. 1.5 million).

Also, the combination of Aphexda and G-CSF allowed 88.3% of patients to undergo transplantation after only one apheresis session compared with the 10.8% given G-CSF alone — an 8.2-fold increase.

All engraftment goals were met, supporting the benefits of combining Aphexda with G-CSF. The combo therapy was found to be safe and well tolerated.

“The clinical outcomes demonstrated by our GENESIS Phase 3 study showed that nearly 90 percent of patients collected an optimal number of cells for transplantation following a single administration of Aphexda and in only one apheresis session,” Serlin said.

An indirect comparative analysis of the cost-effectiveness ratio of the Aphexda-G-CSF combo versus G-CSF plus Mozobil (plerixaflor) — a CXCR4 suppressor approved for stem cell collection — showed the former was linked to a significant drop in health resource use during AHSCT. This translated into net cost savings of around $30,000 and quality-adjusted-life-year benefits.

“We believe Aphexda can become the standard of care in the multiple myeloma transplant setting, while also substantially decreasing healthcare resource utilization across a number of important areas,” Serlin said.