Fighting back against FOP

Regeneron reports encouraging garetosmab Phase 2 results in patients with ultra-rare bone disease

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TARRYTOWN, N.Y.—Regeneron has announced encouraging top-line results from LUMINA-1, a 44-patient Phase 2 trial evaluating garetosmab (REGN2477), an investigational treatment for patients with fibrodysplasia ossificans progressiva (FOP). FOP is a progressive, ultra-rare genetic disorder that causes to abnormal bone formation, which results in skeletal deformities, progressive loss of mobility and premature death. At present, there are no approved treatments. This “extremely clinically meaningful result may alter the course of the disease for people with FOP, (fibrodysplasia ossificans progressiva),” according to Regeneron.
There are approximately 800 patients diagnosed with FOP worldwide, with many others thought to remain undiagnosed or misdiagnosed.
The results of the Phase 2 trial, announced Jan. 9, suggest that treatment can decrease new bone formation and flareups (episodic, localized inflammation).
“After nearly 20 years of researching FOP, Regeneron is excited to share the encouraging results from LUMINA-1,” the company stated Feb. 26. “We are encouraged by these data and look forward to more data later this year, with plans for presentation at a future medical congress, and are eager to discuss this data with the FDA and EMA, so we can find the best path to bring this potential treatment option to people with FOP.”
“Plans for a pediatric study are also in development,” Regeneron adds.
Dr. George D. Yancopoulos, president and chief scientific officer at Regeneron, commented that “This disease is relentless and devastating, leaving many patients wheelchair-bound or locked in a position unable to move, with a dramatically curtailed lifespan. 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.”
In the Phase 2 study, after 28 weeks of treatment, garetosmab decreased total lesion activity (both new and existing lesions) by 25 percent compared to placebo, as measured by PET bone scans (p=0.07). This was driven by a nearly 90-percent reduction in the number of new lesions compared to placebo, as measured by PET.
Garetosmab treatment also led to an approximate 25-percent relative decrease in bone lesion volume (both new and existing lesions) as measured by CT scan (p=0.37), also driven by a nearly 90-percent decrease in the number of new bone lesions as measured by CT. Patients reported 50-percent fewer flareups, and investigator-reported adverse events from flareups were 10 percent for garetosmab and 42 percent for placebo.
In people with FOP, abnormal bone formation occurs in soft tissue outside of the normal skeleton, a process known as heterotopic (in the wrong place) ossification (HO). Regeneron scientists discovered the role of Activin A in FOP, a critical protein in the development of HO, and used VelocImmune technology to invent garetosmab, a monoclonal antibody that reduces the formation of heterotopic bone lesions by neutralizing the Activin A protein.
Most people with FOP are wholly reliant on wheelchairs by 30 years old, and the median age of survival is approximately 56 years. Death often results from complications such as pneumonia, heart failure and aspiration stemming from HO, and loss of mobility in the chest, neck and jaw.
“The prevention of new heterotopic bone is of paramount importance to the treatment of FOP,” stated Dr. Frederick S. Kaplan, The Isaac & Rose Nassau Professor of Orthopaedic Molecular Medicine at The Perelman School of Medicine of the University of Pennsylvania and the global primary investigator for LUMINA-1. “The preliminary results of the LUMINA-1 clinical trial are encouraging as these results clearly show a great reduction in the formation of new lesions, which is incredibly important when we consider future studies in pediatric populations.”
Dr. Marelise Eekhoff, head of the International Amsterdam FOP Expert Center at Amsterdam University Medical Centers (Amsterdam UMC) and a LUMINA-1 investigator states, “The trial is not only a groundbreaking result for people with FOP, but significantly improves our understanding of the disease by demonstrating that untreated people with FOP experience far more frequent and widespread new bone lesions than previously thought, and that these new lesions appear dependent on Activin A for their formation.”
In 2017, the U.S. Food and Drug Administration (FDA) granted Fast Track designation for garetosmab for the prevention of HO in patients with FOP. In the U.S. and European Union, garetosmab has been granted Orphan Designation. The drug is currently under clinical development, and its safety and efficacy have not been evaluated by any regulatory authority.

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