Study to test motixafortide stem cell mobilization for SCD gene therapies
Phase 1 study is effort by BioLineRx, St. Jude Children’s Research Hospital
A second clinical study to test how well BioLineRx’s motixafortide helps mobilize hematopoietic stem cells for use in gene therapies in sickle cell disease (SCD) is expected to begin enrolling in the next few months.
The planned Phase 1 study, called SCDSTEMM (NCT06442761), will run as a collaborative effort between the company and sponsor St. Jude Children’s Research Hospital. Hematopoietic stem cells are blood cell precursors.
The announcement came a few months after the first patient was dosed at Washington University School of Medicine in St. Louis as part of a smaller Phase 1 study (NCT05618301). Initial findings from it are expected later this year.
Like the ongoing study, the one planned for St. Jude and two other clinical sites will test how safe and well tolerated motixafortide is, and how many hematopoietic stem cells can be collected upon treatment.
The success of gene therapies, like the two approved for SCD by the U.S. Food and Drug Administration (FDA) — Casgevy (exagamglogene autotemcel) and Lyfgenia (lovotibeglogene autotemcel) — largely depends on how many stem cells can be moved from a patient’s bone marrow into their bloodstream.
“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,” Ella Sorani, PhD, chief development officer at BioLineRx, said in a company press release.
Mobilizing stem cells
SCD is caused by genetic mutations that result in a faulty version of hemoglobin, the protein that carries oxygen in red blood cells, being produced. The faulty protein tends to clump into rigid threads that deform red blood cells into a sickle-like shape, which are more likely to die prematurely. This can lead to anemia, that is, too few healthy red blood cells. They also tend to stick to the lining of blood vessels, slowing or blocking blood flow to tissues, which can cause episodes of acute pain known as vaso-occlusive crises.
Current approaches to mobilize stem cells for gene therapies are either contraindicated in SCD due to the risk of serious side effects or fail to yield enough cells for genetic manipulation and injection back into the patient to repopulate the bone marrow.
Motixafortide, which is approved for multiple myeloma as Aphexda, blocks the receptor CXCR4 on stem cells. This prevents stem cells from staying in the bone marrow, causing them to move into the bloodstream. Once in the blood, they can then be collected more easily.
“Through this new trial with St. Jude, and our ongoing collaboration with investigators at Washington University School of Medicine in St. Louis, we are excited to be working with leaders in gene therapy and stem cell mobilization to evaluate potential new mobilization options for patients with SCD,” Sorani said.
To expand clinical research, the new study will evaluate motixafortide for mobilizing hematopoietic stem cells from 12 adults with SCD. The study’s main goal is to see if motixafortide is safe and well tolerated. Researchers will also count how many stem cells can be collected after treatment.
The study will have two parts. Part A will test a single dose of the therapy in six patients and Part B will test daily doses over two days in another six patients. In both parts, patients will be given motixafortide via an injection under the skin, or subcutaneously. Researchers will also examine the characteristics of the collected stem cells and their potential for genetic modification.
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