Regeneron Reports Positive Data in Mid-Stage Ultra-Rare Bone Disease Drug Study

Regeneron Pharmaceuticals reported encouraging results from its LUMINA-1 mid-stage study evaluating garetosmab in patients with the ultra-rare bone disease fibrodysplasia ossificans progressive that showed a 225 percent decrease in total bone lesions and a nearly 90 percent reduction in the formation of new lesions in patients taking the drug compared to placebo.

Fibrodysplasia ossificans progressiva (FOP) is a genetic disorder in which muscles, tendons, and ligaments are progressively replaced by bone, a process known as heterotopic ossification (HO), leading to skeletal deformities, progressive loss of mobility, and premature death. There are approximately 800 patients diagnosed with FOP worldwide, with many others thought to remain undiagnosed or misdiagnosed.

Regeneron’s experimental monoclonal antibody garetosmab reduces the formation of heterotopic bone lesions by neutralizing the Activin A protein, which Regeneron found is critical in the development of HO.

“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, vice president of research at Regeneron. “We hope garetosmab can change the course of disease for these long-suffering patients around the world.”

The phase 2, double-blind placebo-controlled LUMINA-1 trial enrolled 44 adult patients with a clinical diagnosis of FOP and documentation of an ACVR1 genetic mutation. Patients in the trial had a range of disease severity from localized functional compromise to near-total immobility.

After 28 weeks of treatment, garetosmab decreased total lesion activity (both new and existing lesions) compared to placebo by 25 percent driven by a nearly 90 percent reduction in the formation of new lesions in patients with FOP. There was also an approximate 25 percent relative decrease in bone lesion volume (both new and existing lesions) compared to placebo. Patient-reported flare-ups were reduced by 50 percent. Investigator-reported adverse events of flare-ups were 10 percent for garetosmab and 42 percent for placebo.

Regeneron plans to use detailed results from this trial as the basis of regulatory submissions. Plans for a pediatric trial are also underway, the company said.

Regeneron has been granted Fast Track and Orphan Drug designations by the U.S. Food and Drug for garetosmab for the prevention of HO in patients with FOP. In the U.S. and European Union (EU), garetosmab has also been granted Orphan Designation in the European Union.

Photo: Aris Economides, vice president of research at Regeneron

Author: Rare Daily Staff