- The Food and Drug Administration ordered a clinical hold on a trial of Solid Biosciences' gene therapy for Duchenne muscular dystrophy after a patient experienced an immune response accompanied with blood, kidney, heart and lung complications.
- The patient was the third in a group receiving the highest dose of Solid's SGT-001 tested so far. Another patient in a group receiving a dose one-fourth as big had a drop in red-blood cell counts, triggering a clinical hold last year.
- Solid's shares fell 70% to $3.32 in early Tuesday trading, their lowest point since the company's initial public offering in early 2018. Since shares reached their highest point last September, Solid has lost $2.4 billion worth of market capitalization, or about 93% of its value.
The race to launch a Duchenne muscular dystrophy gene therapy already has a clear leader in Sarepta Therapeutics. Another major setback for rival Solid should only help solidify that lead.
Solid said the patient in question received a dose of 200 trillion vector genomes per kilogram of body weight at the end of October. He subsequently experienced the triggering of an immune pathway called complement activation, along with a drop in platelet and red-blood cell counts, kidney damage and cardio-pulmonary insufficiency.
Solid reported that the patient "is recovering and continues to improve."
The first clinical hold of SGT-001 also resulted from a patient who experienced complement activation. SVB Leerink analyst Joseph Schwartz wrote in a note to clients that the case announced Tuesday makes two out of six dosed having that immune response. SGT-001's safety, therefore, "will most likely be under increased scrutiny," he said.
It's the third clinical hold placed on a gene therapy in the past two weeks, with a high dose of Novartis' intrathecal version of Zolgensma and Regenxbio's RGX-314 both hitting safety roadblocks with the FDA. The latter of those two was related to the delivery device, and Regenxbio has decided to sue the FDA.
Both Solid and Sarepta, with its gene therapy SRP-9001, seek to help DMD patients gain physical function by replacing a missing gene with a shortened version that can help stimulate production of muscle-building protein. They both use the same delivery mechanism, called adeno-associated virus (AAV).
They have a rival in Pfizer, whose treatment uses a slightly longer, version of the gene than Solid's and Sarepta's do, which in turn produces a bigger version of the protein. Pfizer's gene therapy has faced its own safety woes, with a kidney complication slowing research.
SRP-9001 has been tested in 16 patients at 200 trillion vector genomes per kilogram of body weight without having a clinical hold, noted RBC analyst Brian Abrahams, who covers Sarepta. In a note to clients, he wrote that the better looking safety profile "supports our view that SRP-9001 will likely ultimately make it over the line — increasingly likely as a sole player."