Regeneron's bone disease drug delivers in phase 2, poised for FDA filing

Regeneron’s rare disease drug outshone placebo in a phase 2 study, warding off the majority of new bone formation in adults with a disorder that causes the body’s soft tissues to turn into bone. Full results from the trial will form the backbone of the drug’s regulatory submission. 

The study pitted garetosmab, also called REGN2477, against placebo in 44 patients aged 18 to 60 with the inherited disorder fibrodysplasia ossificans progressiva (FOP). The muscles and soft tissues of people with FOP gradually transform into bone, sometimes spontaneously but often after an injury or illness. This transformation makes movement difficult or impossible. FOP has no treatment, but doctors may prescribe drugs to relieve pain and swelling. 

The patients in the study had varying disease severity—some had difficulty moving specific parts of their body while others had “near-total immobility.” After 28 weeks of treatment, patients taking garetosmab saw a 25% reduction in number of bone lesions, Regeneron said in a statement. The drug also reduced the number of new bone lesions by nearly 90%.  

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"This disease is relentless and devastating, leaving many patients wheelchair-bound or locked in a position unable to move, with a dramatically curtailed lifespan,” said Regeneron President and Chief Scientific Officer George Yancopoulos, M.D., Ph.D., in the statement. “We believe garetosmab may offer important new hope that can potentially transform the course of FOP and look forward to working closely with the FDA and other regulatory authorities to make garetosmab available.” 

Garetosmab is designed to reduce the formation of heterotopic bone—that is, bone in the wrong place—by neutralizing the Activin A protein. The drug also beat placebo at preventing flare-ups, or episodes of localized inflammation. Investigators reported a 10% flare-up rate for the garetosmab arm compared to 42% for placebo. 

"These data prove the hypothesis that Activin A is required for the formation of new heterotopic bone lesions in people with FOP. Activin A inhibition by garetosmab markedly reduced the occurrence of new abnormal bone formation and flare-ups, providing a true opportunity for a disease-modifying therapy for FOP," said Aris Economides, Ph.D., Regeneron’s research chief, in the statement. 

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Although all of the patients in the treatment and placebo groups experienced side effects, all 24 placebo patients and 19 out of 20 garetosmab patients finished the 28-week course of treatment. Most of the side effects were mild to moderate, but two patients in the open-label part of the trial developed serious abscesses that required hospitalization. Both continued on garetosmab. 

In addition to filing the drug for approval to treat adults, Regeneron plans to start testing garetosmab in children. 

Regeneron’s data come shortly after the FDA slapped a clinical hold on two trials of Ipsen’s FOP program, palovarotene, picked up in its $1 billion buyout of Canada’s Clementia. The agency placed the holds on the pediatric portions of a phase 2 study in multiple osteochondromas and a phase 3 study in FOP after reports of growth plate closure in children participating in the latter trial. A few weeks later, Ipsen chief David Meek jumped ship to take the helm of Ferring Pharmaceuticals' gene therapy spinout FerGene.