FDA Slaps Clinical Hold on Solid Bioscience DMD Gene Therapy Program

A U.S. Food and Drug Administration decision to slap a clinical hold on Solid Biosciences’s experimental gene therapy treatment for Duchenne muscular dystrophy sent share prices plunging late Wednesday and into early trading this morning.

Shares are down more than 56 percent to $11.50 in pre-market trading today following the setback. The FDA placed the hold on the Phase I/II IGNITE DMD trial following concerns over the drug’s safety. The FDA’s decision follows closely on the heels of a partial clinical hold the federal regulatory agency placed on its product in November 2017. Solid Biosciences did not publicly disclose that information until January when it made the announcement in a filing with the U.S. Securities and Exchange Commission. The company played that information close to the vest as it was pushing for a $125 million initial public offering of stock.

Solid Biosciences’ lead candidate is SGT-001, a novel adeno-associated viral (AAV) vector-mediated gene transfer under investigation for its ability to address the underlying genetic cause of DMD. SGT-001 is designed to deliver a synthetic dystrophin gene, called microdystrophin, to the body of DMD patients. The company’s belief is that SGT-001 could be a one-time treatment for the devastating disease regardless of genetic mutation or stage of the disease.  

DMD is associated with specific errors in the gene that codes for dystrophin, a protein that plays a key structural role in muscle fiber function. One of the most common fatal genetic disorders, DMD affects approximately one in every 3,500 boys born worldwide. The condition is universally fatal, and death usually occurs before the age of 30.

On Wednesday Solid reported that the first patient in the Phase I/II trial dosed with 5E13 vg/kg of SGT-001 was hospitalized several days later. The patient, who was non-ambulatory, was hospitalized due to "laboratory findings that included a decrease in platelet count followed by a reduction in red blood cell count and evidence of complement activation," the company said. The FDA classified the unexpected event as a Suspected Unexpected Serious Adverse Reaction. During the visit to the hospital the patient showed no signs of coagulopathy, a bleeding disorder, and no relevant changes from baseline in liver function tests.

"The patient responded well to medical treatment and is currently asymptomatic. All laboratory parameters have either improved or returned to normal, and he is continuing outpatient assessments per protocol," the company said in its announcement.

Solid said it will work closely with the FDA to resolve the clinical hold. The FDA will have a number of points to examine before it considers releasing the hold. In addition to the partial hold in November and this most recent hold, the company also has another bit of company drama to examine – the resignation of one of Solid’s scientific advisors and a pioneer in AAV technology.

In January Solid disclosed that gene therapy expert James Wilson, a key member of the company’s scientific advisory board, to resign from the company due to safety concerns. In the same filing disclosing the partial clinical hold, Solid said Wilson "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."

While the shares of Solid Biosciences plunged, shares of rival DMD drugmaker Sarepta Therapeutics (Formerly known as AVI BioPharma, Inc.) jumped overnight and continue to climb in premarket trading. Sarepta announced earlier this week that it intends to seek approval for a second DMD treatment.  

Register as Visitor to CPhI China 2018!