Regeneron Pharmaceuticals, Inc. announced results from LUMINA-1, a 44-patient, Phase 2, double-blind placebo-controlled trial evaluating garetosmab (REGN2477) in patients with fibrodysplasia ossificans progressiva (FOP). FOP is an ultra-rare genetic disorder with no approved treatments that leads to abnormal bone formation resulting in skeletal deformities, progressive loss of mobility and premature death. On the primary analysis after 28 weeks of treatment, garetosmab decreased total lesion activity (both new and existing lesions) compared to placebo by 25% as measured by PET bone scans (p=0.07); this result was driven by a nearly 90% decrease compared to placebo in the number of new lesions, as measured by PET. Correspondingly, there was an approximate 25% 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% decrease in the number of new bone lesions as measured by CT. Patient-reported flare-ups were reduced by 50% (nominal p=0.03). Investigator-reported adverse events of flare-ups were 10% for garetosmab and 42% 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. LUMINA-1 enrolled 44 adult patients (18-60 years old) from North America (U.S. and Canada) and Europe 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. The trial employed 18F-NaF PET imaging and CT scans to investigate the effect of garetosmab on change in HO in patients with FOP. 18F-NaF is a widely approved and extensively used bone-seeking PET tracer with high sensitivity to detect abnormal bone growth, turnover and mineralization in several bone-related diseases such as Paget's disease and cancers with bone involvement. LUMINA-1 has a three-period trial design consisting of a randomized, double-blind placebo-controlled treatment period (6 months), open-label treatment period, during which placebo-treated patients cross over to garetosmab treatment (6 months), and open-label follow-up treatment. The primary analysis was recorded at week 28. During the 28-week treatment period treatment emergent adverse events (TEAEs) occurred in 100% of both treated and placebo groups; the majority were mild to moderate in severity. Notable imbalances in TEAEs included epistaxis (50.0% vs 16.7%) and skin events (madarosis [loss of eyebrows, 25.0% vs 0%], acne [30.0% vs 8.3%] and a composite of skin infections including abscess, carbuncle, folliculitis, furuncle). Two treated patients in the open-label portion of the trial developed serious abscesses requiring hospitalization for drainage but resolved while continuing garetosmab treatment. Nineteen out of 20 garetosmab patients and 24 out of 24 placebo-group patients completed the 28-week treatment period. One patient in the open-label portion of the trial died due to trauma unrelated to treatment. Detailed results from this trial will be used as the basis of regulatory submissions. The data will also be submitted for presentation at a future medical congress. Plans for a pediatric trial are also underway. Fibrodysplasia ossificans progressiva (FOP) is a relentless, progressive, ultra-rare genetic disorder in which muscles, tendons and ligaments are progressively replaced by bone, a process known as heterotopic ossification (HO). There are approximately 800 patients diagnosed with FOP worldwide, with many others thought to remain undiagnosed or isdiagnosed. HO of the jaw, spine, hip and rib cage can make it difficult to speak, eat, walk or breathe, leading to weight loss and escalating loss of mobility and skeletal deformity. People with FOP also experience episodic, localized inflammation known as "flare-ups," although HO may occur both silently as well as in association with symptoms. Most people with FOP are wheelchair bound 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.