- Solid Biosciences Inc. announced that the Food and Drug Administration has placed its Phase 1/2 Duchenne Muscular Dystrophy (DMD) trial on full clinical hold weeks after the first patient was treated.
- That patient in the IGNITE DMD study received 5E13 vg/kg of SGT-001 microdystrophin gene therapy on Feb. 14, and several days later was hospitalized due to lab findings that showed a decreased platelet count and reduced red blood cells.
- The patient showed no signs of bleeding disorders or reduced liver function and has since responded to medical treatment. Solid has halted both enrollment and dosing in the study as it works with FDA to resolve the hold.
Solid Biosciences hit the public market in January 2018, initially pricing its 7.8 million shares at $16 per share, well below its desired range of $18 to $19. Despite that, the biotech still managed to bring in $125 million in proceeds and saw its stock quickly jump above $22 per share.
The stock has performed well — reaching a high at one point of $33 per share, despite the company disclosing in Security and Exchange Commission filings days prior to its IPO that there had been a partial clinical hold put in place by the FDA for its IGNITE DMD trial due to manufacturing concerns related to the high dose of the therapy.
"Prior to dosing patients in our higher-dose group, we will be required to resolve the partial clinical hold on SGT-001 outlined in a November 2017 letter to us from the U.S. Food and Drug Administration, or the FDA. In order to do so we will need to decrease the number of vials and utilize no more than a single production lot per patient and demonstrate that we have the appropriate manufacturing processes in place to support the higher-dose group," said the filing.
The company had said at the time that it could move forward with the trial, but only at low doses.
Shares came crashing down on Thursday, closing the trading day down nearly 65%, at just $9.32, after the clinical hold was upgraded to a full hold based on the latest safety incident.
Solid's therapy works by delivering a dose of a synthetic dystrophin gene — the missing protein in boys with DMD. It is delivered by an adeno-associated viral (AAV) vector. This is a essentially a virus that can be engineered to deliver DNA to a targeted cell; it has become an attractive delivery mechanism for therapies because of its ability to infect both dividing and non-dividing cells. A number of companies use the technology and have not faced clinical holds.
In the Risk Factor section of Solid's S-1 filing with the SEC, the company disclosed that one animal could not be revived during a preclinical toxicology study. "We believe this event was attributed to procedural errors. However, AAV vector cannot be completely ruled out as a contributing factor to the toxicity that gave rise to the event," said the form.
The filing also revealed that gene therapy pioneer James Wilson had resigned from the company's Scientific Advisory Board after "citing emerging concerns about the possible risks of high systemic dosing of AAV."
Competitor Sarepta Therapeutics, which already has a treatment on the market for DMD, is also working to develop a gene therapy that could help cure the devastating pediatric disease. Sarepta's therapy is currently in the early days of in-human testing.