The race to use gene therapy to treat Duchenne muscular dystrophy, a progressive, deadly genetic disease that affects boys, is heating up this week. The FDA just cleared Solid Biosciences to resume clinical testing of a Duchenne gene therapy, a day before Sarepta Therapeutics will report human clinical data from a rival treatment that also uses the approach.
Solid (NASDAQ: SLDB) said this morning that it can restart IGNITE DMD, an early-stage study testing its experimental Duchenne gene therapy SGT-001. The FDA halted the study in March after Solid reported that a patient dosed with the gene therapy was hospitalized for several days. That patient had a decrease in platelet and red blood cells followed by “evidence of complement activation,” or the onset of an immune reaction, and temporary kidney problems, Solid said in a prepared statement.
The company said the patient returned to normal after standard medical care, steroids, and a “limited course” of the Alexion Pharmaceuticals (NASDAQ: ALXN) blood disease drug eculizumab (Soliris) to deal with the immune reaction. Solid said there were no signs of liver damage, abnormal bleeding, or clotting.
“After a thorough analysis of the clinical and laboratory data for the patient, I am confident the event was easily monitored and medically manageable,” said study investigator Barry Byrne, director of the University of Florida’s Powell Gene Therapy Center, in today’s statement. “Our patient quickly returned to his normal activities and planned study assessments.”
Nonetheless, Cambridge, MA-based Solid will now restart IGNITE DMD with a modified protocol. The company will give patients in the trial IV steroids in the “initial weeks” following treatment with SGT-001, make eculizumab available if there are signs of an immune reaction, and use “enhanced monitoring measures” on patients. Solid will also now enroll “several children” before trying the approach on additional adolescents, and may do a muscle biopsy at 45 days of treatment to get more information about the impact the gene therapy is having biologically.
Solid shares surged 11 percent on the news, to $29.50 apiece. They have steadily climbed since the FDA first announced the clinical hold in March and shares plummeted to just over $9 apiece. They closed at $26.50 per share last Friday. Solid went public in January at $16 per share.
Solid is one of a few companies developing a gene therapy for Duchenne, a progressive genetic disease that robs boys of their ability to walk and often kills them from other complications at an early age. There is no cure for Duchenne, just treatments that can help either deal with its symptoms or slow its grim march for some patients. After decades of research, however, gene therapy—which offers the potential of a one-time, possibly long-lasting treatment—is finally being tested in humans with the disease.
But there has been some controversy as human testing has arrived. For one, in its IPO prospectus, Solid disclosed that testing of SGT-001 had been partially suspended since November because of concerns in preclinical studies. Then, days after Solid completed its IPO, gene therapy pioneer James Wilson—who resigned from the company’s scientific advisory board in January—and his colleagues at the University of Pennsylvania published a paper sounding an alarm about the use of gene therapy to treat diseases like Duchenne. Their concerns emerged via animal tests of a potential gene therapy for the rare disease spinal muscular atrophy, but Wilson and colleagues warned that “careful monitoring” is needed in similar settings—that is, when performing a gene therapy procedure by infusing a high dose of adeno-associated viruses (AAV) containing genetic instructions directly into the bloodstream, as Solid is doing.
Along with Solid, Cambridge-based Sarepta (NASDAQ: SRPT) and New York-based Pfizer (NYSE: PFE) are each testing experimental Duchenne gene therapies. But neither Sarepta nor Pfizer have reported any safety problems. Sarepta is in the lead, and will reveal initial results tomorrow of its own Duchenne gene therapy in a few patients. Pfizer dosed its first patient in April and will report data early next year. Because of the clinical hold, Solid will now report its first interim data from the trial in the second half of 2019.
Solid will hold a conference call this morning to discuss the news.
[Solid CEO and founder Ilan Ganot is pictured above with his son, Eytani.]