[Updated, 1/26/18, see below] Solid Biosciences was expected to ride gene therapy’s wave of recent momentum to an IPO this week. But new revelations have clouded the offering, as the company revealed just before going public that its most advanced drug candidate has been under FDA scrutiny since mid-November.
The gene therapy, SGT-001, is being developed to treat Duchenne muscular dystrophy, an inherited disease that affects boys, often robbing them of the ability to walk in their teens and killing them at a young age. Now that the FDA has approved its first-ever gene therapy, Duchenne is widely seen as one of the next targets for the field; SGT-001 is one of four either in human clinical testing or slated to start this year.
[Updated with pricing details] The news was delivered Thursday through a regulatory filing, hours before Solid raised roughly $125 million by selling 7.8 million shares at $16 apiece (It will make its Nasdaq debut on Friday morning). Solid revealed that testing of SGT-001 has been partially suspended since November. The FDA’s “partial clinical hold,” as it is known, has stopped Solid from administering a high dose of its gene therapy to patients in its early-stage clinical study. The company said it is allowed to continue testing a lower dose.
According to Solid, the FDA wants Solid to ensure that it has the “appropriate manufacturing processes in place to support the higher-dose group.” Solid said it “doesn’t expect overall timing for clinical development to be affected.”
A spokesperson declined to comment further, citing an SEC-mandated “quiet period” that limits what a company can say to the public near an IPO.
The disclosure is the second in the span of nine days to cast a shadow over Solid’s program. On Jan. 16, also through a regulatory filing, Solid revealed that James Wilson, a gene therapy pioneer at the University of Pennsylvania, had resigned as the chair of the company’s scientific advisory board on Jan. 11. Wilson cited “emerging concerns about the possible risks” involved with the procedure, according to the filing. The filing also disclosed possible safety concerns in animal testing—one monkey in a preclinical test on a high dose of SGT-001 was euthanized. Solid “believe[s] the event was attributed to procedural errors,” though it couldn’t rule out the possibility that the virus used to deliver the gene therapy was a contributing factor.
Taken together, the disclosures raise questions about the push to use gene therapy for Duchenne. Side effects stemming from immune reactions to the engineered virus that delivers the restorative gene would resurface a problem that has haunted the field in the past.
Wilson has played a key role in that history. He co-led the study at UPenn that led to the death of teenager Jesse Gelsinger in 1999, a development that chilled investment in gene therapy work for many years. Continuing his lab work, however, Wilson helped advance the gene therapy delivery tool known as an adeno-associated virus, or AAV, which has become a critical part of gene therapy’s renaissance. Wilson’s AAV work led to a company called RegenXBio (NASDAQ: [[ticker:RGNX]]), which has deals in place with a number of gene therapy developers.
Wilson did not return a request for comment, and a UPenn spokeswoman deferred questions back to Solid.
Others working on Duchenne gene therapy responded quickly to the Solid revelations.
One high-profile doctor involved in a study of a different Duchenne gene therapy says he hasn’t seen safety problems, either in animals during preclinical testing or in the one patient who has received the treatment. “We have followed FDA guidelines. We’ve done similar toxicology studies in similar animals and haven’t seen any toxic effects,” said Jerry Mendell, the director of the gene therapy center at Nationwide Children’s Hospital in Columbus, Ohio.
Mendell has treated Duchenne patients for more than four decades. One patient in a study—one of two that Sarepta Therapeutics (NASDAQ: [[ticker:SRPT]]) is backing at Nationwide—hasn’t had
