Product information and disease description Place of product in therapy Approaches to treatment Current treatment options and standard of care

Limitations of current therapies

5 evidence topics · 9 sources

Summary: limitations of therapies available before and after the 2026 approvals

The international clinical guideline states that no medication has been proven to alter the natural history of fibrodysplasia ossificans progressiva and that its evidence-based statements are "generally moderate to low". Its management rests on injury avoidance and symptomatic treatment of flare-ups; corticosteroids are limited to 4-day courses started within 24 hours of onset, and no definitive evidence shows that NSAIDs, COX-2 inhibitors, bisphosphonates, or off-label agents prevent flare-ups or heterotopic ossification. The guideline predates the approvals of garetosmab-grts (August 2026) and zilurgisertib (September 2026) and lists both as investigational Class III agents.

Until 2026, palovarotene was the only approved therapy. Its approval rested on post hoc analyses against an external natural history control after the prespecified month-18 analysis showed no statistically significant difference, and at month 48 the 46.4% lower annualized new HO volume was not significant (nominal p = .0585). Premature physeal closure occurred in 24 of 80 participants younger than 18 years (30.0%), all younger than 14 years, and the European Medicines Agency refused marketing authorisation. Garetosmab-grts is labeled for adults only, requires intravenous infusion every 4 weeks, and did not show a statistically significant difference in new HO volume. Zilurgisertib is not established in patients younger than 12 years. No approved therapy is labeled for females younger than 8 years or males younger than 10 years. Fidrisertib, a second ALK2 inhibitor, did not meet its primary endpoint in 113 participants.

No medication proven to alter the natural history

“At the present time, there are limited treatments for FOP.” (opens the source at this quote in a new tab)
“PHYSICIANS TREATING PATIENTS WHO HAVE FOP SHOULD KEEP IN MIND THAT NONE OF THESE MEDICATIONS (OR ANY OTHER MEDICATIONS TO DATE) HAVE BEEN PROVEN TO ALTER THE NATURAL HISTORY OF FOP” (opens the source at this quote in a new tab)

Strength of the evidence behind guideline recommendations

“As FOP is an ultra-rare condition, evidence-based statements are generally moderate to low.” (opens the source at this quote in a new tab)
“In the absence of clear evidence-based research from controlled clinical trials, it is difficult to advocate a particular therapy with enthusiasm.” (opens the source at this quote in a new tab)

Standard of care limited to symptom management, and constraints in growing patients

“The current standard of care (SoC) for FOP is limited to symptom management and flare-up prevention.” (opens the source at this quote in a new tab)
“This may limit the ability to treat growing patients with palovarotene and thus highlights the need for additional disease-modifying therapies for these individuals.” (opens the source at this quote in a new tab)

Multiple pathway nodes under investigation, with no approach yet established as most effective

“The development of therapies for FOP have focused on targeted inhibition of the ACVR1 receptor, ACVR1 ligands, BMP pathway signaling, preosseous chondrogenic anlagen of HO, and inflammatory triggers of disease activity (Figure 1).” (opens the source at this quote in a new tab)
“Currently, it is too early to determine which one of these approaches or combinations of approaches will be most effective in FOP, and all are being studied intensively in preclinical and/or clinical studies” (opens the source at this quote in a new tab)