Shares of a small biotech company went stratospheric this week following news that its gene therapy had cured several children with a rare immune-deficiency disease.
St. Jude Children’s Research Hospital in Memphis, Tennessee, said Wednesday that it had cured several children with X-linked severe combined immunodeficiency, or SCID-X1. The disease, whose sufferers are born with no immune system and usually die very early in life, is often called “bubble boy” disease for the plastic protection systems in which they must spend their lives. But according to the hospital, the patients in its trial were producing functional immune cells – including T cells, B cells and natural killer cells – for the first time. So far, 10 patients have been treated, and a publication of data on eight has appeared Thursday in the New England Journal of Medicine.
The exact incidence of X-SCID is unclear, according to the National Institutes of Health, but it likely occurs in 1-in-50,000 to 100,000 newborns, much more frequently in males than in females. It may be more common in people with Turkish, Navajo or Apache ancestry, according to the National Organization for Rare Disorders.
Worcester, Massachusetts-based Mustang Bio is handling commercial development of the gene therapy, under the development name MB-107, with a 28-patient Phase I/II trial currently underway. In response to the news, shares of Mustang opened up 200 percent on the Nasdaq Thursday morning – at $8, from their $2.66 Wednesday closing price – and were still up 112 percent Friday morning. The trial is taking place at St. Jude and at the University of California San Francisco. MB-107 is a lentiviral vector-based gene therapy.
According to the NEJM paper, patients first received bone marrow ablation with busulfan in order to clear up space for the gene therapy. After infusion, they were followed for a median 16.4 months. Within three to four months, seven of the infants showed normalized numbers of immune cells, and the eighth showed T cell development after a boost of gene-corrected cells. As of the infants’ last follow-up, four had infections or ulcers that had received, four were no longer receiving intravenous immunoglobulin, and four had been vaccinated.
Special credit was given to UCSF, which played an important role in the treatment protocol by including targeted busulfan. According to the article, previous trials of a lentiviral vectors without bulsulfan produced growth of T cells, whereas B cell, myeloid cell and NK cell growth was relativley low, thereby resulting in insufficient immunity. The authors pointed out that busulfan conditioning in allogeneic stem cell transplantation in infants with genetic SCID was controversial and considered unnecessary in certain settings because “T-cell reconstitution is regularly achieved without conditioning and is sufficient for early patient survival.” However, most patients did not have reconstitution of functional B cells, and their T-cell immunity waned over time, meaning they had to receive additional therapies such as bone marrow transplantation and gene therapy.
Photo: jxfzsy, Getty Images