FDA Approves Garetosmab-grts, First Treatment for FOP Bone Growth

Adults living with fibrodysplasia ossificans progressiva (FOP), an ultrarare genetic disorder in which muscle, tendon, and ligament are progressively replaced by bone, now have their first FDA-approved therapy. The FDA approved garetosmab-grts (Pasatru; Regeneron) to reduce the formation of new heterotopic ossification (HO) lesions and clinician-assessed flare-ups in adults with FOP, providing pharmacists with a novel monoclonal antibody to dispense and monitor for a population that has had no approved disease-directed option.¹

A First Option for a Burdensome Disease

FOP is driven by rogue bone formation, or HO, that infiltrates connective tissue and can immobilize the jaw, spine, hip, and rib cage. This can make it difficult to speak, eat, walk, or breathe. Roughly 900 people worldwide are diagnosed with FOP; most are wheelchair-bound by age 30, and the median age of survival is approximately 56 years. Garetosmab is a VelocImmune-derived, fully human monoclonal antibody that binds and neutralizes activin A, a protein identified as central to HO development in FOP.¹

OPTIMA Trial Efficacy

Approval rests on the OPTIMA trial (NCT05394116), a multicenter, multinational, placebo-controlled phase 3 study that enrolled 63 adults 18 years and older with an FOP-causing variant of the type I activin A receptor and a cumulative analog joint involvement scale score at screening of 19 or lower. Participants were randomly assigned to intravenous (IV) garetosmab at either 10 mg/kg (n = 23) or 3 mg/kg (n = 19), or placebo (n = 21) once every 4 weeks for 56 weeks.^1-3

At 56 weeks, both doses met the primary end point of reducing total new HO lesions as assessed by CT: an approximate 90% reduction with 10 mg/kg (2 vs 19 lesions) and a 94% reduction with 3 mg/kg (1 vs 19 lesions) vs placebo. For the key secondary end point of clinician-assessed flare-ups, the approval release reported 9 flare-ups with 10 mg/kg (88% reduction), 53 with 3 mg/kg (15% reduction), and 66 with placebo. Changes in patient-reported flare-ups through week 56 did not differ significantly between groups.¹

Dosing, Safety, and Counseling

The recommended starting dose is 10 mg/kg, administered IV over 60 minutes once monthly; it may be reduced to 3 mg/kg over 60 minutes monthly if not tolerated. Because many patients face significant mobility challenges, garetosmab can be administered across care settings, including home infusion, where appropriate. This is a logistics point pharmacists coordinating rare-disease infusions should note.¹

“The starting dose and subsequent titration should be determined through an individualized discussion between the physician, the patient, and caregivers, balancing the potential benefit of greater suppression of heterotopic ossification and flare-ups against the safety profile at that dose,” Kathryn McCrystal Dahir, MD, professor of medicine at Vanderbilt Health and lead investigator of OPTIMA, told Pharmacy Times. “Factors such as disease severity and activity, the patient’s treatment goals, prior infections or other adverse events, and their tolerance of therapy should all inform that discussion.”

Safety counseling is central. Garetosmab carries warnings for embryo-fetal harm; patients who can become pregnant should have a pregnancy test before starting and use effective contraception during treatment and for 6 months after the last dose.

“Pregnancy should be excluded before treatment, and effective contraception should be used throughout therapy and for 6 months after the final dose; treatment should be stopped immediately if pregnancy occurs,” Dahir cautioned.

Skin and soft-tissue infections, including abscesses and cellulitis, and epistaxis—some of them serious—have occurred. Among all 63 participants, serious treatment-emergent adverse events (AEs) occurred in 2 patients on 10 mg/kg, 1 on 3 mg/kg, and 2 on placebo. The most common AEs (10% or greater frequency) were abscess, acne, increased hair growth, madarosis, oral ulcers, epistaxis, folliculitis, paronychia, and rash.¹

“Patients should be encouraged to have frequent reporting and open communication of possible early signs and symptoms to their prescribing physician,” Dahir noted.

What Comes Next

A regulatory submission is under review by the European Medicines Agency, with additional filings planned, including in Japan. OPTIMA 2, a phase 3 trial enrolling children and adolescents, is scheduled to begin later this year.¹

REFERENCES

1. Pasatru (garetosmab-grts) first and only FDA-approved treatment demonstrating reduction in new heterotopic ossification (HO) lesions and clinician-assessed flare-ups in a placebo-controlled trial in adults with fibrodysplasia ossificans progressiva (FOP). News release. Regeneron. August 19, 2026. Accessed August 19, 2026. https://investor.regeneron.com/news-releases/news-release-details/pasatrutm-garetosmab-grts-first-and-only-fda-approved-treatment

2. Regeneron announces positive phase 3 trial in adults with ultra-rare genetic disorder fibrodysplasia ossificans progressiva (FOP), demonstrating that garetosmab prevents greater than 99% of abnormal bone formation. News release. Regeneron. September 17, 2025. Accessed August 19, 2026. https://investor.regeneron.com/news-releases/news-release-details/regeneron-announces-positive-phase-3-trial-adults-ultra-rare

3. A study to assess safety, tolerability and efficacy of garetosmab versus placebo administered intravenously (IV) in adult participants with fibrodysplasia ossificans progressiva (FOP) (OPTIMA). ClinicalTrials.gov. Updated July 17, 2026. Accessed August 19, 2026. https://clinicaltrials.gov/study/NCT05394116