First Patient Dosed in RAG1-SCID Gene Therapy Trial


Mustang Bio plans to add more clinical trial sites in the near future.

Mustang Bio has dosed the first participant with recombinase-activating gene-1 (RAG1) severe combined immunodeficiency (RAG1-SCID) with MB-110 in a phase 1/2 clinical trial (NCT04797260) in Europe.

“The patient was administered LV-RAG1 without any complications. LV-RAG1 allowed the patient’s body to create a functioning immune system, which is responding well to the standard vaccinations for newborns,” principal investigator Arjan Lankester, MD, PhD, Professor of Pediatrics and Stem Cell Transplantation, Leiden University Medical Centre, said in a statement.

MB-110 is an ex vivo gene therapy using the LV-RAG1 lentiviral vector. LV-RAG1 was developed by Frank J. Staal, PhD, Leiden University Medical Centre, with whom Mustang entered an exclusive, worldwide license agreement to use the vector in 2021. MB-110 addresses the mutations in the RAG1 gene to achieve immune reconstitution. The therapy has been granted orphan drug designation by the European Medicines Agency.

The trial is primarily assessing feasibility of successful generation of RAG1 LV CD34+ cells and the safety of MB-110 as measured by overall survival and event-free survival (EFS) after infusion. Secondary endpoints include T-cell reconstitution, thymic function, T and B cell receptor repertoire, immunoglobulin dependence, persistence of gene marking, occurrence of infections, failure to thrive, and quality of life. Mustang is planning to add more clinical trial sites in the near future.

READ MORE: Lentiviral Gene Therapy for Infants With X-Linked SCID Helps Build ‘Functional’ Immune System

“This first successful administration to a RAG1-SCID patient of a stem-cell based gene therapy represents a significant positive step forward for our MB-110 development program... XSCID and RAG1-SCID make up almost 60% of all SCID cases combined. We look forward to continuing to advance these clinical candidates, including plans to initiate a multicenter pivotal Phase 2 trial for MB-107 under Mustang’s IND in the second half of this year,” Manuel Litchman, MD, president and chief executive officer, Mustang, added to the statement.

CGTLive previously spoke with Bruce Dezube, MD, senior vice president and head, clinical development, Mustang Bio, for this year’s Rare Disease Day to learn more about the rare diseases that Mustang Bio is targeting, including SCID, glioblastoma, and chronic lymphocytic leukemia. He discussed importance of Rare Disease Day as well as the role of collaboration and advocacy to improve rare disease awareness and therapy development.

“Rare disease brings together government agencies, including both the funding and the regulatory agencies, pharmaceutical industries, and patient advocates. And, their priorities can sometimes differ... These different groups are involved with every aspect [of therapy development] and every aspect is working, but every aspect could be working even better,” Dezube told CGTLive.

Mustang Bio announces first patient successfully treated by ex vivo lentiviral gene therapy to treat RAG1 severe combined immunodeficiency. News release. Mustang Bio. July 27, 2022.
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