1st SCD patient dosed in proof-of-concept study of motixafortide
Small trial testing agent's safety, efficacy for stem cell mobilization
A small proof-of-concept clinical trial evaluating motixafortide for stem cell mobilization — regimens essential for gene therapies — in sickle cell disease (SCD) has dosed its first patient.
Stem cell mobilization regimens currently available can cause serious side effects in SCD patients. This Phase 1 study (NCT05618301), which plans to enroll five adults with SCD, will assess whether motixafortide, alone or in combination with other agents, is a safer and more efficient alternative to these regimens.
Initial data from the study, conducted by motixafortide’s developer BioLineRx, in collaboration with the Washington University School of Medicine in St. Louis, Missouri, is expected in the second half of this year.
“This is an exciting area of clinical research with the potential to meaningfully increase patients’ access to stem-cell based gene therapies,” Zachary Crees, MD, principal investigator for the trial, whose single study site is at the Washington University School of Medicine, said in a press release.
Investigating motixafortide for possible use in SCD gene therapy
Gene therapies aim to restore the production of healthy hemoglobin, the oxygen-carrying protein in red blood cells that is defective in people with SCD.
Two such therapies were approved late last year by the U.S. Food and Drug Administration (FDA): Casgevy (exagamglogene autotemcel) and Lyfgenia (lovotibeglogene autotemcel).
These treatments involve harvesting a patient’s CD34-positive hematopoietic stem cells — cells in the bone marrow that can give rise to other types of blood cells. These cells are then edited in a lab and returned to the patient via a stem cell transplant.
To ensure enough cells are collected for the procedure, patients are given a mobilization agent to stimulate the movement of these stem cells out of the bone marrow and into the bloodstream.
However, standard mobilization agents may not reliably yield the desired number of stem cells. Moreover, granulocyte-colony stimulating factor (G-CSF), a commonly used mobilization agent, is contraindicated, or not recommended, for SCD patients as it can cause serious side effects, including painful vaso-occlusive crises.
“Stem-cell based gene therapy has delivered significant progress in the treatment of sickle cell disease; however, identifying novel mobilization approaches that safely and reliably secure the necessary stem cell collection numbers is clinically relevant for patients,” Crees said.
Motixafortide (sold as Aphexda) is one such mobilization agent that works by blocking the protein CXCR4, which functions to keep stem cells inside the bone marrow. Its ability to increase stem cell mobilization has been successfully demonstrated in other diseases, such as multiple myeloma, a blood cancer.
The new study is evaluating motixafortide alone and in combination with natalizumab, an antibody-based therapy for multiple sclerosis (sold as Tysabri) that also can mobilize hematopoietic stem cells.
Stem-cell based gene therapy has delivered significant progress in the treatment of sickle cell disease; however, identifying novel mobilization approaches that safely and reliably secure the necessary stem cell collection numbers is clinically relevant for patients.
The trial will assess the safety and tolerability of both mobilization regimens in adults with SCD undergoing red blood cell exchanges. Specifically, it will measure the number of mobilized cells and the collection speed.
“The recent FDA approvals of two gene therapies for sickle cell disease in the U.S. is an exciting development for the sickle cell community, and we are eager to advance clinical research of motixafortide that may potentially lead to additional CD34 [positive] hematopoietic stem cell mobilization options in the future for patients with this condition,” said Ella Sorani, PhD, chief development officer at BioLineRx.
“We’d like to thank the patients participating in this important collaboration with Washington University who are helping to advance the field’s understanding in this area where there is unmet need,” Sorani said.
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