RARE Daily

FDA Places Hold on Mustang Bio’s XSCID Gene Therapy

January 26, 2022

The U.S. Food and Drug Administration has placed a hold on Mustang Bio’s New Drug application for MB-207, its experimental gene therapy for X-linked severe combined immunodeficiency, also known as bubble boy disease.

Photo: Manuel Litchman, president and CEO of Mustang

X-linked severe combined immunodeficiency (XSCID) is a rare genetic disorder that occurs in approximately 1 per 225,000 births. It is characterized by the absence or lack of function of key immune cells, resulting in a severely compromised immune system and death by 1 year of age if untreated. Patients with XSCID have no T-cells or natural killer cells. Although their B-cells are normal in number, they are not functional. As a result, XSCID patients are usually affected by severe bacterial, viral, or fungal infections early in life and often present with interstitial lung disease, chronic diarrhea, and failure to thrive.

Among patients who receive hematopoietic stem cell transplantation, many are unable to establish adequate T-cell immunity or lose T-cell immunity over time. Further, approximately two-thirds of patients who receive HSCT lack sufficient B-cell immunity and need lifelong immunoglobulin replacement therapy.

MB-207 is a lentiviral gene therapy for the treatment of patients with XSCID severe combined immunodeficiency, also known as bubble boy disease, who have been previously treated with a hematopoietic stem cell transplantation and for whom re-treatment is indicated. The FDA has previously granted MB-207 Orphan Drug and Rare Pediatric Disease designations. If MB-207 is approved by the FDA, it would be eligible for a rare pediatric disease voucher.

An additional phase 1/2 clinical trial for XSCID in newly diagnosed infants under the age of two is ongoing at St. Jude, UCSF Benioff Children’s Hospital in San Francisco, and Seattle Children’s Hospital. The product candidate in this trial is designated as MB-107.

The FDA previously granted Rare Pediatric Disease, Orphan Drug and Regenerative Medicine Advanced Therapy Designations to MB-107 for the treatment of XSCID in newly diagnosed infants. Additionally, the European Medicines Agency granted Advanced Therapy Medicinal Product Classification, Orphan Drug and PRIME designation to MB-107.

Mustang expects to initiate a multi-center pivotal phase 2 clinical trial of MB-107 under a Mustang-sponsored IND in newly diagnosed infants with XSCID who are between two months to two years of age in the third quarter of 2022. The trial is expected to enroll 10 patients who, together with 15 patients enrolled in the current multi-center trial led by St. Jude, will be compared with 25 matched historical control patients who have undergone HSCT. The primary efficacy endpoint will be event-free survival.

“In light of our positive experience managing the prior MB-107 CMC hold, and our ability to secure FDA clearance to proceed with that program, we believe that our CMC team is well positioned to address the Agency’s concerns around MB-207 once additional clarification of the hold becomes available,” said Manuel Litchman, president and CEO of Mustang. “Furthermore, we remain fully committed to the success of the pivotal Phase 2 MB-207 clinical trial for children with XSCID who have previously received HSCT and require re-treatment.”

Author: Rare Daily Staff

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