Study: Regeneron's garetosmab reduces bone lesions in patients with fibrodysplasia ossificans progressiva

Regeneron Pharmaceuticals said Thursday that the experimental drug garetosmab decreased total lesion activity, consisting of both new and existing lesions, by 25% versus placebo in a Phase II study of patients with fibrodysplasia ossificans progressiva (FOP). The company indicated that based on the results it plans to discuss marketing applications with regulatory authorities. 

The LUMINA-1 trial included 44 adults with FOP and documentation of an ACVR1 genetic mutation. Regeneron noted that study participants had a range of disease severity from localised functional compromise to near-total immobility. LUMINA-1 consisted of a six-month treatment period in which patients were randomised to receive either garetosmab or placebo, a six-month open-label treatment period during which patients in the placebo group cross over to garetosmab, and open-label follow-up treatment. Investigators used 18F-NaF positron emission tomography (PET) imaging and computed tomography (CT) scans to assess the effect of garetosmab on change in heterotopic ossification, with the primary analysis recorded at week 28. 

Regeneron reported that the 25% decline in total lesion activity in garetosmab-treated patients was driven by a nearly 90% decrease in the number of new lesions, compared to placebo, as measured by PET. The company said CT scans also revealed a corresponding 25% relative decrease in total bone lesion volume, driven by a nearly 90% reduction in new bone lesions. Meanwhile, patient-reported flare-ups were reduced by half, while investigator-reported adverse events of flare-ups were 10% for garetosmab and 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," remarked Aris Economides, vice president of research at Regeneron. The executive added "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." 

According to Regeneron, garetosmab, also known as REGN2477, is a VelocImmune-derived fully-human monoclonal antibody that binds and neutralises Activin A, which is involved in heterotopic bone formation in FOP. The company noted that trial planning for garetosmab in paediatric patients is underway. In 2017, the FDA granted garetosmab fast-track status for the prevention of heterotopic ossification in patients with FOP, while the drug has also received an orphan designation in the US and Europe. 

In February last year, Ipsen agreed to acquire Clementia Pharmaceuticals for up to $1.3 billion to gain access to palovarotene, a RAR-gamma agonist in Phase III testing to treat FOP. The company later also signed a deal with Blueprint Medicines for up to $535 million for exclusive rights to BLU-782, an ALK2 inhibitor in Phase I testing for FOP. For related analysis, see ViewPoints: Ipsen keeps boning up on FOP

Meanwhile, BioCryst Pharmaceutical is also developing drug candidates for FOP, namely BCX9250 and BCX9499. 

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