Solid Biosciences Discloses DMD Trial Setback Amid $125M IPO Push

Solid Biosciences' failure to disclose some negative issues related to its work on a treatment for Duchenne muscular dystrophy (DMD) not only complicated its upcoming initial public offering (IPO), but is casting some shade on DMD research in general.

As John Carroll, with Endpoints News, writes, “In most IPOs, risk factors can range from anything from ‘our lead drug may not work’ to the threat of famine and plague—they’re intended to cover virtually every contingency.”

What Solid Biosciences failed to share, as it was building support for its $125 million IPO, was that the U.S. Food and Drug Administration (FDA) had placed a partial clinical hold on its product in November 2017. The company was only allowed to begin testing at its lowest dose. But Solid only filed that information with the U.S. Securities and Exchange Commission (SEC) today.

They also didn’t publicize that one of the key members of their scientific advisory board, gene therapy expert James Wilson from the University of Pennsylvania, had resigned over the safety concerns. Their last-minute filing stated, “Recently, James M. Wilson, MD, PhD, resigned from our Scientific Advisory Board citing emerging concerns about the possible risks of high systemic dosing of AAV. If in the future we are unable to demonstrate that any such adverse events were not caused by the administration process or related procedures, the FDA, the European Commission, the EMA or other regulatory authorities could order us to cease further development of, or deny approval of, SGT-001 or our other product candidate for any or all targeted indications.”

Solid, on its part, indicates that the FDA wanted to ensure the company had the “appropriate manufacturing processes in place to support the higher-dose group.” It also said it “doesn’t expect overall timing for clinical development to be affected.”

Gene therapy typically depends on using adeno-associated virus (AAV) as a vector for introducing the replacement gene. Apparently one of the monkeys used in testing at its high-dose treatment had to be euthanized. The company indicates it “believe[s] the event was attributed to procedural errors.” However, it can’t rule out that it might have been caused by the virus.

In 1999, Wilson was co-leader of a gene therapy study that led to the death of teenager Jesse Gelsinger. Wilson’s work since has led to AAV becoming a critical and relatively safe component of gene therapy. The revelation, or at least hints, that AAV may have caused problems with a DMD gene therapy is putting many on the industry into a defensive crouch.

Jerry Mendell, director of the gene therapy center at Nationwide Children’s Hospital in Columbus, Ohio, told Xconomy, “We have followed FDA guidelines. We’ve done similar toxicology studies in similar animals and haven’t seen any toxic effects.” Mendell is involved in two gene therapy clinical trials run by Sarepta Therapeutics. He says, “As far as I can see, we have a very safe product.”

And Pfizer which is involved in gene therapy for DMD, also indicates it hasn’t identified any preclinical data that would prevent it from moving into human testing.

“Whatever is going on with Solid that has required the chairman of their scientific advisory board to resign in protest and has acquired the FDA to place them on clinical hold is, to the best of our knowledge, something unique to whatever is going on at Solid,” Doug Ingram, Sarepta’s chief executive officer, told Xconomy. “It probably would benefit all of us, and the patient community, if Solid would provide more information about exactly what is going on with their program that is causing problems.”