Fulcrum rises on trial failure

Sometimes biopharma investors ought to expect the expected. A phase 2b trial of Fulcrum Therapeutics’ losmapimod in a rare muscle disorder, having failed at the interim analysis, has duly failed at the final one. Redux4 had aimed to show that the p38 MAPK inhibitor could reduce Dux4-driven gene expression – aberrant expression of Dux4 in skeletal muscle causes the muscle degeneration that characterises facioscapulohumeral muscular dystrophy. No such reduction was seen. Fulcrum tried to claim significance for some of the other endpoints, including muscle fat infiltration, a measure of upper extremity range of motion and function and patients’ self-reported change in feel and function, but an asterisked disclaimer in its statement admitted that the p values it had given were nominal. Remarkably, the company’s contention that the trial had failed because Dux4 expression varies between patients and is hard to measure appears to have convinced: the group’s shares are up 7% in early trading. The company intends to discuss a path forward with the FDA, and as the days when the agency might have regarded a non-significant hit on a surrogate endpoint with scepticism are long past, perhaps this strategy has merit.

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