RARE Daily

FDA Removes Clinical Hold on Mustang Gene Therapies for SCID

February 2, 2021

Rare Daily Staff

Mustang Bio said the U.S. Food and Drug Administration has lifted a clinical hold on its MB-107 pivotal phase 2 clinical trial and Investigational New Drug application, and will initiate a pivotal phase 2 study in newly diagnosed patients with the rare condition X-linked severe combined immunodeficiency.

The lift came after the agency reviewed a comprehensive chemistry, manufacturing, and controls package that was submitted by Mustang in late December 2020.

X-linked severe combined immunodeficiency (XSCID) is a rare genetic disorder. 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 (NK)-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 HSCT, 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.

The specific genetic disorder that causes XSCID is a mutation in the gene coding for the common gamma chain (γc), a protein that is shared by the receptors for at least six interleukins. These interleukins and their receptors are critical for the development and differentiation of immune cells. The gene coding for γc is known as IL-2 receptor gamma, or IL2RG. Because IL2RG is located on the X-chromosome, XSCID is inherited in an X-linked recessive pattern, resulting in almost all patients being male.

The same lentiviral vector used in MB-107 is currently being assessed in a phase 1/2 clinical trial for XSCID in newly diagnosed infants under the age of 2 at St. Jude Children’s Research Hospital, UCSF Benioff Children’s Hospital in San Francisco, and Seattle Children’s Hospital. Additionally, it is being assessed in a phase 1/2 clinical trial at the National Institute of Allergy and Infectious Diseases for XSCID patients who have been previously treated with hematopoietic stem cell transplantation and for whom re-treatment is indicated.

“The clinical outcomes observed in XSCID patients in the ongoing phase 1/2 clinical trials continue to be encouraging,” said Manuel Litchman, president and CEO of Mustang. “It is especially gratifying to see the consistent safety and efficacy of our lentiviral vector over the course of more than eight years since the first patient was treated at NIAID in 2012.”

Photo: Manuel Litchman, president and CEO of Mustang

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