Ten months after saying its losmapimod treatment had performed no better than placebo in an interim analysis, Fulcrum Therapeutics once again has said the oral drug failed to meet the primary endpoint.
The news comes just one month after the FDA granted fast track designation to Fulcrum for the potential treatment in patients with facioscapulohumeral muscular dystrophy (FSHD). The setback comes amid a recent shake-up to the leadership team, which got a new chief medical officer in May and an internally promoted CEO in March.
Fulcrum said Thursday losmapimod did not show changes in DUX4-driven gene expression, which was included in the phase 2b trial as an experimental biomarker endpoint. FSHD is a rare, progressive disease with no approved treatment.
Fulcrum picked up the molecule from GlaxoSmithKline in 2019 with commitments of up to $37.5 million in clinical and regulatory milestones. Fulcrum had believed the asset might block expression of DUX4 in treating the progressive muscle wasting disorder, after the drug led to no success for GSK in a cardiovascular disease indication.
The company’s trial was the first major clinical test of that hypothesis, and it came up short once again in the 48-week analysis.
Despite the headline news, Fulcrum is pushing ahead with the drug as it believes it has “strong support” for “meaningful” clinical benefit in what it saw as relevant measures.
“We are thrilled with the data reported from ReDUX4,” said Fulcrum CEO and President Bryan Stuart in a statement. “These results showing consistent reduction in fat infiltration and correlating benefit on multiple measures with losmapimod represent a major advance for the potential treatment of this devastating disease.”
The treatment showed statistically significant and clinical relevant benefits across structural, functional and patient reported endpoints, including decreasing muscle fat infiltration and improved reachable workspace. Fatty infiltration in lean muscle tissue is correlated with severity of the FSHD disease, the company said. Reachable workspace, or the measure of range of motion and function in the upper body, is important, as FSHD typically progresses from the upper to lower body.
These silver linings are giving the company hope for its meetings with health authorities, including the FDA, slated for the second half of this year, to determine next steps on the regulatory journey.
Fulcrum reported no treatment-related discontinuations or related serious adverse events from the equally randomized, double-blind trial of 80 patients, who were given 15 mg of losmapimod twice per day. The company extended the trial from 24 to 48 weeks as a result of the COVID-19 pandemic.