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Fulcrum's Phase 3 for old GSK drug fails, stock sinks

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Fulcrum Therapeutics reported a Phase 3 fail Thursday morning, sending its stock plummeting.

The biotech said that a study testing the former GSK cardio drug losmapimod in facioscapulohumeral muscular dystrophy (FSHD) missed its primary endpoint and several secondary measurements. Fulcrum shares $FULC were down more than 65% Thursday, dropping from $8.85 at Wednesday’s close to about $3 apiece.

“In light of these results, we plan to suspend the losmapimod program in FSHD,” CEO Alex Sapir said in a statement.

Losmapimod’s development history stretches back years, with GSK expecting big things from the drug in the early- to mid-2010s. GSK had hoped it could prevent repeat heart attacks and launched an ambitious clinical program in high-risk heart failure and COPD, but the last research was scuttled in 2016 after multiple trial failures.

Fulcrum licensed the drug three years later, aiming to repurpose it for FSHD, a rare genetic disease where patients’ muscle dies and is replaced by fat. After a Phase 2 study missed its primary in 2020, Fulcrum tried to move forward by highlighting a potential effect in a subpopulation of patients with high expression of the DUX4 gene that plays a major role in FSHD.

After 48 weeks, however, the Phase 3 revealed almost no difference between the primary endpoint’s active and placebo arms, with a p-value that came in at p=0.75. Fulcrum said three other secondary endpoints also missed statistical significance.

Leerink analyst Joseph Schwartz previewed the readout earlier this week. He expected Fulcrum might have had a chance at approval if the trial showed some signal toward a benefit, given that there are no approved treatments for FSHD. The company had several shots on goal to make this effort even if the primary endpoint failed and the “bar may not be as high as one might think,” he wrote.

But Thursday’s results were clear-cut, as Fulcrum announced it would pause development of losmapimod in FSHD. Schwartz had estimated a 30% chance of a clear failure, compared to a 20% chance of everything going well and 50% odds of being able to move forward with messy data.


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