After more than 10 years in development, Regeneron secured a landmark approval for its monoclonal antibody garetosmab, now commercially known as Pasatru. The drug has become the second cleared by the FDA to treat fibrodysplasia ossificans progressiva (FOP) and the first to reduce clinician-assessed flare-ups in adults with the disease.
Pasatru, given intravenously every four weeks, is designed to block what is believed to be the key protein behind the FOP disease process—activin A—which was pinpointed by Regeneron scientists as a possible target for treating FOP more than a decade ago.
The approval follows a victory last year in a phase 3 study, which randomized 63 adults with FOP to receive one of two doses of the anti-activin A antibody or placebo every four weeks for 56 weeks. In the trial, both high- and low-dose Pasatru reduced new bone lesions in FOP patients by 90% over 56 weeks. And high dose Pasatru reduced bouts of painful localized inflammation by 89% compared to placebo, too.
By the end of the trial, an independent data monitoring committee recommended all patients on placebo be switched to Pasatru as soon as possible.
FOP is an ultrarare genetic disorder—there are roughly 900 cases worldwide—wherein the body’s soft tissues progressively turn to bone. It’s marked by painful flare-ups: hot and swollen masses in the tissue that precede the permanent conversion of muscle, tendons and ligaments to bone. Over time, the ossification restricts patient movement, and the pain becomes chronic as the increasing bone mass compresses nerves and fuses joints.
“It is a particularly cruel disease that is very unpredictable,” Susan Rhee, M.D., executive medical director of clinical sciences at Regeneron and clinical program lead for Pasatru, told Fierce. Patients can be relatively stable and then wake up one morning to find their jaw or shoulder has locked overnight.
The approval is a “huge milestone” for both Regeneron and “the incredibly resilient community” of FOP patients, Rhee said. “We’re just so thrilled to be able to translate our science into a potential product for these patients.”
Pasatru won its go-ahead thanks to data from the late-stage Optima trial linking the 10- and 3-mg/km doses of the drug to 90% and 94% reductions in lesions versus placebo, respetively, Regeneron said in a release Wednesday.
The approval will make Pasatru available to the roughly 220 adult FOP patients in the U.S. But launching a drug in the rare disease category is no small feat, especially when the broader patient population hovers around or below just 1,000 confirmed cases worldwide.
The drug’s only competitor, Sohonos, gained approval in 2023 but underperformed at launch due to low patient uptake, a high price tag and its side effect profile. In the drug’s pivotal trial, 8% of enrollees permanently discontinued treatment due to adverse events. Ipsen took a loss of 279 million euros ($330 million) tied to the product in 2024.
“One of the greatest challenges is, widely, a lack of familiarity within physician and patient communities with FOP,” John Ryan, Regeneron’s head of global rare disease commercial business unit, said in an interview with Fierce. Part of the drugmaker’s mission, he said, is to increase awareness about FOP beyond academic centers and FOP specialists to improve time to diagnosis and treatment.
The drug is expected to be available “very quickly after approval,” but Regeneron declined to comment on Pasatru’s list price. Ryan said the company is “committed to supporting patients’ access,” adding that those efforts will include things like “providing financial assistance for eligible patients, including co-pay support,” and “free medicine for people who meet certain criteria.”
Pasatru was slated for FDA filing in 2021 after delivering promising phase 2 results but stalled out due to concerning safety data in late 2020. Five of the 44 patients in the drug’s trial at the time died. While there was no clear link to Pasatru as the cause of death, researchers said it could not be ruled out and plans for FDA filing were temporarily dropped.
Safety became the priority of the approval-winning phase 3 Optima trial, which went on to report no deaths or serious bleeding events. No patients receiving Pasatru discontinued treatment, either, per Regeneron.
There was one serious treatment-emergent adverse event in the low-dose group and two in the high-dose group compared to two in the placebo arm. The strong safety profile was welcome relief for the patient community and the Regeneron team, alike. “There were tears,” Rhee said of the research team’s reaction
Regeneron has plans to pursue approval outside the U.S. and to launch a pediatric FOP trial later this year, Rhee said. “The time to treat is as early as possible. So, we’re very keen on getting a pediatric trial started as soon as possible,” she said.