- Executives from Solid Biosciences believe the "totality" of new results from an early-stage trial show that an experimental gene therapy the biotech has been developing is having a positive impact on patients with Duchenne muscular dystrophy.
- The results, from three patients given a high dose of Solid’s treatment one year ago, however, are mixed. Changes on a commonly used test of motor function fell short of expectations. But on a conference call Monday afternoon, Solid executives pointed to patients’ apparent improvement on a variety of other measurements as evidence of a treatment benefit.
- Solid’s program is one of three gene therapies in advanced testing for Duchenne, one of which, from Pfizer, is already in a Phase 3 trial. Though each treatment appears to help patients produce a small, modified version of the muscle-protecting protein they lack, it’s unclear if, as long hoped, they can change the trajectory of the progressive and fatal disease.
In what was supposed to be a defining year for gene therapy in Duchenne, more questions have been raised than answered.
The field’s first-ever data from a randomized, placebo controlled trial, a study run by Sarepta Therapeutics, disappointed in January. Though the company blamed its results on bad luck in the patient randomization process — and still has the chance to prove the theory later this year — that outcome lowered the expectations for the other gene therapies in development. The result also triggered doubt that the treatments, which each help patients produce "micro" or "mini" versions of the dystrophin protein they lack, can slow or stop the progression of the disease.
But Sarepta’s setback did leave an opening for Pfizer and Solid to gain ground. Pfizer, which once trailed Sarepta, became the first to begin a Phase 3 study. And Solid, whose gene therapy was twice stalled due to safety concerns, was able to restart testing and move its program forward.
The technology underlying each program is slightly different, which could lead to different product profiles. Solid’s gene therapy, for instance, has led to less microdystrophin production than the others. But its treatment produces a different type of dystrophin, which some analysts have suggested might lead to more potent results.
That isn’t clear, however, from the data Solid released Monday afternoon, which come from the first three patients to get a high dose of its gene therapy in its early-stage study. Forty-eight weeks after treatment, the three patients saw their scores on the North Star Ambulatory Assessment, a 17-item scale commonly used to gauge motor function in Duchenne, climb by an average of 0.3 points.
That result is better than what would be expected of those Duchenne patients, who were roughly 7 to 11 years of age at the start of the trial and thus expected to sharply decline each year. But the number is lower than the 1.0 point mean improvement in those who got a lower dose. It also fell short of what Sarepta reported, albeit it can be tough to compare across trials and Sarepta tested its treatment in younger patients. Shares of Solid fell about 30% in early trading Tuesday morning.
On a conference call with analysts, however, Solid chief medical officer Cathryn Clary pointed to the "totality of the data" the company reported. Patients had relatively high NSAA scores at the start of the trial, which may have made it harder to see a treatment effect, she said. Solid reported improvements in patients’ lung function, as well as on a standard test measuring how far they can walk in six minutes. It also reported encouraging signs on a series of patient-reported outcomes, which tracked their ability to function and perform daily activities over time. And since changing its trial protocol and upgrading its manufacturing work, Solid hasn’t seen the same safety concerns that caused testing to be stopped.
"We believe that examining the totality of these endpoints will help clinicians, patients and parents understand potential benefits that [treatment] may have on the trajectory of the disease," Clary said.
Analysts had differing views of Solid’s presentation. Raymond James analyst Danielle Brill noted that the positive results Solid cited varied widely between patients, making the data hard to square. "At the end of the day, these effects are relatively modest, difficult to interpret, and are not too convincing," Brill wrote. SVB Leerink’s Joseph Schwartz conceded the variability, but pointed to positive signs "across a broad range of clinical outcomes."
Those other outcomes may become more relevant for Solid as time goes on. The company is currently working through the design of a Phase 3 trial, and Clary said that Solid isn't sure if the NSAA, which is the current gold standard study goal in Duchenne, would be the primary endpoint. The company is exploring composite or alternative measures based on data it collects in the study.
“While it remains to be seen if the FDA would be open to alternative endpoints, we are intrigued by the possibility,” SVB analyst Schwartz wrote.
Solid hasn’t said when it plans to start a late-stage study.