Dive Brief:
- Solid Biosciences restarted dosing of SGT-001 microdystrophin gene therapy in the Phase 1/2 IGNITE Duchenne muscular dystrophy (DMD) clinical trial earlier this year after a clinical hold, and has announced the dosing of two additional patients.
- The resumption of dosing was "complemented by continued work on our innovative and scalable manufacturing process, which enabled us to move forward with the study as planned and without delay," the biotech's CEO Ilan Ganot said in a Nov. 13 statement.
- Concerns about the therapy's safety arose after researchers dosed the first patient in that trial, but there were no serious adverse events seen in the second or third patients dosed. Enrollment is ongoing, with six patients randomized to either the active treatment or the delayed treatment group.
Dive Insight:
Improvements in manufacturing have helped Solid BioSciences move forward IGNITE, which is evaluating SGT-001 in DMD patients. That's a good position to be in, considering manufacturing has proved to be a stumbling block for other gene therapy developers.
Key competitor Sarepta Therapeutics, for instance, also had a Phase 1/2a trial of its microdystrophin gene therapy put on clinical hold earlier this year after a manufacturing problem left trace levels of DNA fragments in research-grade plasmids. Sarepta has turned to a contract development and marketing organization (CDMO), Paragon Bioservices, to support it in upscaling to commercial manufacturing.
"We are encouraged by the company working to improve their scalable manufacturing capabilities ... since manufacturing will become increasingly more important as gene therapies near market," Joseph Schwartz, analyst at Leerink, wrote in an investor note.
"We believe that the company’s current 250 liter scale could be poised to gain higher scale and yield, positioning them favorably, assuming SGT-001 is approved and gets to market," Schwartz added.
IGNITE appears to be getting past some of the turbulence it experienced earlier this year. In July, the FDA lifted a clinical hold placed on the trial when the first patient treated with SGT-001 experienced an unexpected adverse event. The patient recovered fully after a drop in platelet counts, transient renal impairment and signs of complement activation, which could indicate an immune reaction.
Since restarting, Solid said there was a transient decline in platelet count, but it was "quickly identified and managed per the study protocol." The company expects preliminary biopsy data in the first quarter of 2019 and an interim analysis to roll out sometime in the first half of next year.
SGT-001 has fast track designation from the FDA. Schwartz believes this, along with the FDA recognizing there are limited treatment options for DMD and other rare diseases, could mean the agency will be more flexible toward a speedier regulatory pathway.
"Furthermore, we view the trial design of IGNITE Ph.1/2 study (active group vs delayed treatment control group) conducive to collecting more patient data that could help support an expedited path forward," Schwartz wrote.
Solid's R&D expenses have gone up to $14.7 million for the third quarter of 2018, compared with $10.6 million for the same quarter in 2017. According to the company in its third quarter earnings release, the increase was primarily due to personnel- and facility-related expenses in clinical development and manufacturing for SGT-001, as well as other pipeline products.