Mustang Bio, a Fortress Biotech Company, and St. Jude Children’s Research Hospital have entered into an exclusive worldwide license agreement for the development of a first-in-class ex vivolentiviral gene therapy for the treatment of X-linked severe combined immunodeficiency (“X-SCID”), also known as bubble boy disease. X-SCID is the most common form of severe combined immunodeficiency, affecting approximately one in 50,000 to 100,000 newborns worldwide.

The therapy, which includes a low dose of busulfan prior to reinfusion of the patients’ own gene-modified blood stem cells, is currently being evaluated in a Phase 1/2 multicenter trial in infants under the age of two at St. Jude, UCSF Benioff Children’s Hospital San Francisco; and Seattle Children’s Hospital. This study, led by Ewelina Mamcarz, M.D., Assistant Member at St. Jude, is the world’s first lentiviral gene therapy trial for infants with X-SCID. In addition, the therapy is being investigated in patients over the age of two in a second Phase 1/2 trial at the National Institutes of Health (“NIH”). The therapy was developed in the laboratory of Brian Sorrentino, M.D., Director of the Division of Experimental Hematology at St. Jude.

Eight patients under the age of two with X-SCID have been treated to date, with results presented at the 21st Annual Meeting of the American Society of Gene & Cell Therapy in May 2018. The therapy was well tolerated. In addition, six patients achieved reconstituted immune systems within three to four months following treatment, with the remaining two patients continuing to progress favorably in earlier stages of recovery. Two of these six patients have discontinued monthly infusions of intravenous immunoglobulin, and the remaining patients, at earlier stages of recovery, continue to progress favorably. In three patients who had disseminated infections prior to therapy, all infections resolved completely.

“Our therapy has been well tolerated thus far, and none of the infants required any blood product support after low dose of busulfan,” Dr. Mamcarz said. “Most importantly, we observe recovery of all cells of the immune system, which is truly an achievement over prior gene therapy trials, where B cell reconstitution did not occur, and patients required intravenous immunoglobulin for life.”

Mustang and St. Jude believe there may be as many as 1,000 to 1,500 patients in the U.S. with X-SCID, as well as a similar number in Europe, who continue to have significant impairment of immunity despite receiving previous allogeneic stem cell transplantation and who therefore could be eligible for this gene therapy. 

Manuel Litchman, M.D., president and chief executive officer of Mustang, said, “We are thrilled to announce the expansion of our pipeline into gene therapy for patients with X-SCID, a natural fit for our Worcester, Mass. cell processing facility. We look forward to working with St. Jude to advance this program through ongoing Phase 1/2 trials, with the goal of providing a novel, long-term treatment to the more than 80 percent of infants who lack fully matched bone marrow transplant donors and those patients who continue to have significant impairment of immunity. With our team’s extensive expertise in viral vector design, manufacturing and transduction, we are building a fully integrated cell and gene therapy company, with the goal of leveraging the transformative potential of these technologies to bring life-saving treatments to patients in need.”