Rare Daily Staff

Mustang Bio said it entered into an exclusive worldwide license agreement with St. Jude Children’s Research Hospital for the development of a first-in-class gene therapy for the treatment of X-linked severe combined immunodeficiency, or bubble boy disease.

Boys with the condition are at risk of recurrent infections because their immune system is unable to defend against common pathogens. Babies with X-SCID usually do not live beyond infancy. X-SCID is the most common form of severe combined immunodeficiency, affecting approximately one in 50,000 to 100,000 newborns worldwide.

Mustang and St. Jude believe there may be as many as 1,000 to 1,500 patients in the United States 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.

The therapy, which includes a low dose of the chemotherapeutic agent 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. The study 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.

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. 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. The therapy was well tolerated.

In the NIH study, which was reported in the April 2016 issue of Science Translational Medicine, five patients aged 10 to 23 years with progressively declining persistent immune dysfunction after haploidentical hematopoietic stem cell transplant in infancy were treated with the ex vivo lentiviral gene therapy.

The therapy appeared to be safe, and follow-up data from two older patients demonstrated immune system reconstitution and clinical improvement at 2 to 3 years following treatment. In three younger patients, similar levels of gene-modified immune cells were also observed at 6 to 9 months following treatment.

“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,” said Manuel Litchman, president and CEO of Mustang. “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.”

August 14, 2018
Photo: Manuel Litchman, president and CEO of Mustang