Just four months after Sanofi bet $80 million in upfront cash on Fulcrum Therapeutics’ losmapimod, the program has ended in a phase 3 failure.
The licensing deal with the Big Pharma was agreed upon while counting down to the release of late-stage data in the progressive muscle wasting disorder facioscapulohumeral muscular dystrophy (FSHD) which, if successful, could have opened the door to the p38 inhibitor becoming the first approved therapy for the disease.
But the results are just in, and it looks like a wipeout. Not only did the 260-patient study miss its primary endpoint of showing an improvement in an individual’s arm reach when taking a 15-mg losmapimod tablet twice a day compared to placebo, but the study’s secondary endpoints like muscle fat infiltration and patient-reported improvements “did not achieve nominal statistical significance,” Fulcrum explained in a Sept. 12 premarket release.
Specifically, the primary endpoint of reachable workspace (RWS)—an analysis of how far an individual can reach—saw a 0.013 improvement among patients receiving losmapimod at Week 48 compared to a 0.010 improvement among those who received placebo.
Fulcrum’s chief medical officer Pat Horn, M.D., Ph.D., blamed the results on the lack of deterioration among the placebo cohort.
“These results in patients receiving losmapimod when compared to baseline were similar to those observed in our phase 2 study,” Horn said. “However, in contrast to what was seen in the ReDUX4 study as well as what has been reported in other FSHD studies, the patients receiving placebo in REACH did not show a decline in functional status as measured by RWS and shoulder dynamometry over the 48 weeks of the study.”
The safety and tolerability of losmapimod was consistent with previously reported studies, according to Fulcrum, which said it will fully evaluate the data before sharing the results at an upcoming medical meeting.
“We are deeply disappointed that the REACH trial did not replicate the clinical results observed in the phase 2 ReDUX4 trial,” Fulcrum’s CEO Alex Sapir said in the release. “In light of these results, we plan to suspend the losmapimod program in FSHD.”
The biotech’s stock plummeted 70% in premarket trading Thursday morning to $2.60 from a Wednesday closing price of $8.85.
Massachusetts-based Fulcrum said it would use its $273.8 million in cash and equivalents to swiftly pivot to its remaining pipeline. This is headed up by pociredir, a phase 1-stage small molecule designed to treat sickle cell disease by increasing expression of fetal hemoglobin.
Today’s results mark a fork in the road for Fulcrum, which could have been on track to get the first-ever FSHD drug to market if the phase 3 data had shown promise. Losmapimod had a two- to three-year head start on Roche’s myostatin inhibitor that is being targeted at FSHD, while Avidity Biosciences and Arrowhead Pharmaceuticals both have antibody-oligonucleotide complexes in clinical development for the condition.
It also means Fulcrum can wave goodbye to potentially $975 million in milestone payments that were tied to the Sanofi licensing deal. When the French Pharma secured the ex-U.S. rights to losmapimod in May, the drugmaker’s global head of rare disease Burcu Eryilmaz pointed to “meaningful clinical benefits” shown in phase 2 studies that “underscore the disease-modifying potential and opportunity to address the high unmet need for a safe and effective drug that slows disease progression.”
But losmapimod already had a number of clinical misses on its scorecard. Fulcrum rescued the molecule in 2019 from the vault of GSK, where losmapimod had failed a phase 3 trial in patients with acute coronary syndrome and a midstage study in chronic obstructive pulmonary disease.
Under its new owner, it had also failed a phase 2 trial in FSHD in 2021, although Fulcrum was heartened by phase 2b data showing losmapimod could still slow disease progression and improve function in FSHD patients.
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