- Solid Biosciences announced Monday that one of two patients in the "dose-escalation" phase of its Duchenne muscular dystrophy gene therapy trial experienced liver enzyme elevations and platelet declines that researchers determined were related to the treatment.
- The dose was four times what earlier patients were given, a level that did not stimulate higher levels of microdystrophin, which is an approximation of the key muscle-building protein missing in DMD.
- The data cast doubt on Solid's ability to compete against Sarepta Therapeutics, which is nearing the end of dosing of its microdystrophin gene therapy. Pfizer is also in this space, with data from its mini-dystrophin gene therapy expected at a conference next month. Shares in Solid tumbled 29% Tuesday to their lowest levels since the company's initial public offering in early 2018.
Duchenne muscular dystrophy represents a small population of patients, so the first company to reach the market with a one-time treatment — as gene therapy is designed to be — will be at a considerable competitive advantage.
Monday's announcement by Solid casts some doubt on whether its entrant, SGT-001, can find a safe therapeutic window, much less catch up to Sarepta's candidate, known as AAVrh74.MHCK7.Micro-dystrophin.
Dose escalation is a common practice to establish an optimal safe and effective dose, and Solid knew it needed to increase the number of gene-carrying viral vectors it injected into patients after the first try disappointed.
In the first two patients exposed to the new dose levels, however, one experienced what was in essence three adverse events. The patient had a gastrointestinal infection determined to be unrelated to SGT-001, along with a drop in platelet levels and elevation of transaminases and bilirubin that were judged to be related to the gene therapy.
Solid reported that liver enzyme levels had fallen following treatment with glucocortioids, while the platelet levels returned to normal on their own. Still, researchers viewed the liver-related side effects as a "serious adverse event," a declaration that could lead to a review of trial protocols.
For example, Spark Therapeutics has been using a course of steroids for its hemophilia A gene therapy SPK-8011 in order to prevent liver enzyme elevations.
It doesn't help that SGT-001 had been subjected to a clinical hold thanks to a previous patient experiencing a drop in platelet counts. This time, however, Solid is continuing to enroll patients and expects to be able to share more data later this year.
Sarepta, meanwhile, has continued to push its microdystrophin gene therapy through the clinic, with a late March update showing improvements in both biomarkers and functional tests in four patients who have completed nine months of follow-up since their initial treatment. A trial of commercial-scale gene therapy is expected to begin later this year.
And Pfizer appears to be close to revealing two- and 12-month muscle biopsy data from a Phase 1 trial of its mini-dystrophin project PF-06939926 at the Parent Project Muscular Dystrophy conference in June.
A company with the marketing might of Pfizer needs to be watched closely whenever it enters a space against smaller competitors.
However, SVB Leerink analyst Joseph Schwartz wrote in a May 10 note to clients that Sarepta is at least a year ahead of Pfizer, giving it that important early-mover advantage. Moreover, Pfizer's project is dosing at three times the level of Sarepta's candidate, which raises questions of whether Pfizer's could have more side effects.