- Solid Biosciences can resume a trial of its experimental gene therapy for Duchenne muscular dystrophy. The company announced Thursday that the Food and Drug Administration will allow the study's continuation after Solid improved its manufacturing and enrollment procedures.
- The trial of SGT-001 was put on hold twice because of side effects in two patients, with one experiencing kidney damage as well as reduced heart and lung function. The side effects were linked to activation of a part of the immune system known as the complement pathway.
- Solid is in a three-way race with Pfizer and Sarepta Therapeutics to prove out a gene therapy in Duchenne muscular dystrophy, or DMD, but the clinical holds have put it behind its two rivals. The company's shares more than doubled in morning trading, but are still valued at less than one-tenth their all-time high, hit in September 2018.
In spite of two FDA approvals, gene therapy remains in its infancy. Developers are attempting to navigate a tricky path between delivering enough genetic material to correct disease-causing mutations, but not so much as to expose patients to too much of the viruses that are used to carry corrective genes into cells.
Solid's therapy appeared to miss that balance, triggering the two holds that have significantly set back progress on the company's IGNITE-DMD trial, which so far has enrolled six of a planned 16 patients. The patients were split into two groups, the first three receiving a dose of 50 trillion vector genomes per kilogram of body weight and the second three receiving 200 trillion.
The third patient in that latter group experienced multiple complications involving the kidneys, heart, lungs and blood. This resulted in the FDA stopping the study to review the safety data.
In a release Thursday, Solid said the agency agreed to lift the hold after reviewing new manufacturing and enrollment procedures.
The company said it refined its manufacturing so most empty viral protein shells are removed, allowing for lower viral exposure at the 200 trillion vector genome dose. To pass FDA muster on this change, the company had to demonstrate the therapy produced by the new manufacturing practice would stimulate production of a similar amount of muscle-building protein as did the old process.
The next two patients receiving the 200 trillion vector genome dose must weigh no more than 18 kilograms, again to reduce viral exposure. Based on safety data from those two, the company could potentially dose heavier children afterwards.
While Solid continues to study patients to identify the best dose for pivotal trials, its rivals are nearing milestones that could lead to asking the FDA for approval.
Sarepta could submit its treatment to regulators next year, using data from placebo-controlled trials, plus early data from a study that will test its gene therapy made with a manufacturing-scale process.
Pfizer, meanwhile, announced Thursday it has received Fast Track designation for its gene therapy, which will speed review if its data are positive. The big pharma expects to start a Phase 3 trial by the end of the year, which could yield data in 2022.