Solid Biosciences has given its Duchenne muscular dystrophy (DMD) gene therapy without causing the sort of adverse events that forced it to shutter the study in 2019. The experience provides early evidence that the manufacturing changes and clinical mitigation strategy could rescue the program.
Dosing in Solid Bio’s IGNITE DMD clinical trial stopped after three of the first six recipients of the gene therapy developed four serious adverse events. Two of the adverse events related to activation of the terminal pathway of the classical complement system. Activation happened in all six patients but only led to serious adverse events twice.
After amending the protocol and manufacturing process, Solid Bio got the green light to resume the study. Limited data from the first participant treated under the revised protocol are now available.
Solid Bio said the seventh patient “was dosed safely with mild to moderate adverse events, all of which have fully resolved.” The lack of serious adverse events provides early evidence that Solid Bio’s changes have had the desired effect, with the big caveat that it has only treated one patient. That one subject still had complement activation but at substantially lower levels than the other patients.
Having cleared that early safety test, Solid Bio is now screening additional subjects. The next patient will need to meet the 18-kg weight limit imposed to reduce total viral load and, in doing so, cut the risk of adverse events. Solid Bio may later adjust weight upward, relying on manufacturing changes that reduced viral load and pretreatment with Soliris to mitigate the threat of adverse events.
The small step forward represented by the safe dosing of the seventh patient still leaves Solid Bio a long way back in the DMD gene therapy race. Pfizer and Sarepta Therapeutics have more advanced candidates, although the failure of the latter company in a randomized trial in January shows their path to market is far from certain.
Solid Bio shared an update on the six subjects who received the gene therapy under the old protocol, none of whom have suffered further serious adverse events. The small size and open-label nature of the study make it hard to draw firm conclusions, particularly in light of how Sarepta stumbled when it moved into a larger, randomized trial, but the update offers some encouragement.
Overall, Solid Bio saw a slight improvement in North Star Ambulatory Assessment scores in recipients of the gene therapy, compared to a 4.0 decline in the untreated control cohort. The gene therapy group also performed better on the six-minute walk test and an assessment of pulmonary function.
Investors need convincing that Solid Bio is back on track. Shares in the biotech fell 15% premarket.