- An experimental gene therapy to treat Duchenne muscular dystrophy (DMD) failed to yield significantly higher levels of microdystrophin protein in three patients, according to preliminary three-month biopsy data released Thursday by Solid Biosciences, the treatment's developer.
- Although Solid's CEO said he remains confident in the company's approach, the results disappointed investors and analysts who had hoped to see the gene transfer treatment, called SGT-001, spur increased expression of microdystrophin — an approximation of the crucial dystrophin protein missing in DMD patients.
- Data from two patients showed no microdystrophin via a testing method known as Western blot and "very low levels" via another, called immunofluorescence, Solid stated. The third patient had slightly better results, showing protein expression in about 10% of fibers via immunofluorescence and some expression via Western blot, but below the 5% threshold. Company execs last month put out expectations of at least 10% expression based on preclinical data, according to SVB Leerink analyst Joseph Schwartz.
Wall Street's reaction to the underwhelming results was swift, sending shares in Solid down more than 70% in Thursday morning trading. The company went public a little more than a year ago, several years after launching with a mission to cure DMD, an inherited muscle-wasting disease almost always seen in boys.
Solid faced setbacks in advancing study of its treatment, receiving a partial clinical hold on the Phase 1/2 IGNITE study in November 2017. The hold, since resolved, prevented Solid from dosing patients in a higher-dose group due to manufacturing concerns.
In March 2018, however, Solid was hit with another regulatory hold after reports emerged of a serious adverse event in the first patient dosed in the study. By June, the Food and Drug Administration lifted the hold following that patient's recovery.
Altogether, Solid has enrolled six patients in the IGNITE study, with three in the active treatment arm and three in a delayed treatment control group. The three for whom data were released Thursday all received the lowest dose level in the study protocol.
Company executives noted the safety profile continues to be adequate and unchanged, with no additional serious adverse events.
The company plans to move forward by expediting its dose escalation strategy. At current funding levels, the company expects to be able to operate through early 2020.
However, the plan to escalate dose levels could renew safety concerns the company has faced before. About a year ago, James Wilson, a pioneer in gene therapy, resigned from Solid's scientific advisory board after "citing emerging concerns about the possible risks of high systemic dosing" by an adeno-associated viral vector, a company filing disclosed.
Sarepta Therapeutics remains the leader in the DMD space, RBC Capital's Brian Abrahams wrote in a Feb. 7 note to investors. While Solid's results are at a dosing level about one-fourth of Sarepta's, Abrahams stated he still believes the "not so-solid" data "should help reduce one of the competitive overhangs" on Sarepta.
The other major player in the space is Pfizer, with its own DMD gene therapy results expected to read out this quarter.