Regeneron Pharmaceuticals (REGN) has secured a landmark FDA approval for its monoclonal antibody garetosmab, now commercially known as Pasatru, after more than ten years in development.
The drug becomes the second FDA-cleared treatment for fibrodysplasia ossificans progressiva, known as FOP, and the first shown to reduce clinician-assessed flare-ups in adults living with the condition.
FOP is an ultrarare genetic disorder affecting roughly 900 people worldwide, in which the body’s soft tissues progressively and permanently convert to bone.
The disease is marked by painful flare-ups involving hot, swollen masses in tissue that precede the irreversible conversion of muscle, tendons, and ligaments into bone over time.
As ossification advances, patients lose movement, suffer chronic pain from nerve compression, and experience joints fusing without warning.
“It is a particularly cruel disease that is very unpredictable,” said Susan Rhee, M.D., executive medical director of clinical sciences at Regeneron and clinical program lead for Pasatru.
Rhee noted that patients can be relatively stable and then wake up one morning to find their jaw or shoulder has locked overnight, illustrating the disease’s brutal unpredictability.
Pasatru, administered intravenously every four weeks, is designed to block activin A, the key protein believed to drive the FOP disease process, which Regeneron scientists identified as a target more than a decade ago.
The approval was supported by data from the phase 3 Optima trial, which randomised 63 adults with FOP to receive one of two doses of the drug or placebo every four weeks across 56 weeks.
Both the 10-mg/kg and 3-mg/kg doses of Pasatru reduced new bone lesions by 90% and 94% versus placebo, respectively, according to data Regeneron released alongside the approval announcement.
High-dose Pasatru also reduced bouts of painful localised inflammation by 89% compared with placebo, a result that marked a significant clinical advance over existing treatment options.
By the trial’s conclusion, an independent data monitoring committee recommended that all patients on placebo be switched to Pasatru as soon as possible given the strength of the results.
Importantly, the phase 3 trial reported no deaths, no serious bleeding events, and no patients discontinuing Pasatru treatment, addressing safety concerns that had previously delayed the drug’s regulatory path.
Pasatru had been slated for FDA filing in 2021 following promising phase 2 results but stalled after five of 44 trial patients died in late 2020, with researchers unable to rule out a link to the drug.
The approval is a “huge milestone” for Regeneron and “the incredibly resilient community” of FOP patients, Rhee said, adding: “We’re just so thrilled to be able to translate our science into a potential product for these patients.”
The drug will now be available to approximately 220 adult FOP patients in the United States, a narrow but critically underserved population with very few therapeutic options.
Pasatru’s only competitor, Sohonos, received approval in 2023 but underperformed commercially due to low patient uptake, a high price tag, and a challenging side effect profile that led to permanent discontinuation in 8% of pivotal trial enrollees.
Ipsen recorded a loss of 279 million euros, equivalent to around $330 million, tied to Sohonos in 2024, underscoring the commercial difficulty of launching drugs in ultra-rare disease categories.
“One of the greatest challenges is, widely, a lack of familiarity within physician and patient communities with FOP,” said John Ryan, Regeneron’s head of global rare disease commercial business unit.
Ryan said Regeneron is committed to expanding awareness beyond academic centres and FOP specialists, and confirmed the company will offer financial assistance, co-pay support, and free medicine for patients meeting certain eligibility criteria.
Regeneron declined to disclose Pasatru’s list price but said the drug would be available very quickly after approval, with plans to seek regulatory clearance outside the United States and to begin a paediatric FOP trial later this year.