Zilurgisertib Could Give FOP Patients a Third Treatment on September 26th

Roughly 300 people in the United States live with fibrodysplasia ossificans progressiva, a genetic disease in which muscle, tendon, and ligament gradually turn into bone. Researchers at the University of Pennsylvania, who identified the causative gene in 2006, describe what forms as a second skeleton. Extra bone bridges across joints and locks them in place, one by one, until reaching for a shelf or turning to look over a shoulder becomes impossible. The disease has been in the medical literature since the 1600s. For nearly all of that time, there was nothing to prescribe for it.

That has changed with startling speed. On September 25th, the FDA approved zilurgisertib, a once-daily pill from Mirum Pharmaceuticals and Incyte, as Atebrioz. That makes it the third FOP treatment cleared in just over 3 years, in a disease that measured its history in centuries of waiting. The story of how a 300-person disease suddenly has a crowded pipeline, and what this particular decision rested on, is worth telling in full.

Why FOP Builds a Second Skeleton

Nearly everyone with FOP carries the same single-letter mutation in a gene called ACVR1, which builds a bone-growth receptor known as ALK2. The mutation leaves that receptor stuck partway on, so signals that should only fire during skeletal development keep firing in adults, telling muscle and connective tissue to become bone. The process moves in episodes called flare-ups: painful, swollen periods, often triggered by a bump, a fall, or even an intramuscular injection, that frequently end with a new piece of permanent bone. This is why FOP care has long revolved around avoiding harm. Biopsies, dental injections, and minor surgeries can all set off new bone growth, and the misdiagnosis rate is high because early symptoms look like tumors or aggressive fibrosis.

The 3 drugs now converging on this disease attack that biology at 3 different points, which matters more than it might seem. More on that below.

Sohonos (palovarotene), a retinoid from Ipsen, became the first approved FOP treatment in August 2023. Its road was rough. The FDA had rejected an earlier filing, European regulators refused to authorize it, and BioPharma Dive reported that the eventual US clearance came "despite questions about its benefits" (BioPharma Dive, 2023). Retinoids also carry real burdens, including skin and mucosal side effects and a risk of early growth plate closure that requires careful monitoring in growing children. Sohonos was still the first approved option for a disease that had none.

The pace picked up in 2026. On August 19, 2026, the FDA approved Regeneron's Pasatru (garetosmab), an antibody given by intravenous infusion that blocks Activin A, a protein that the mutant ALK2 receptor mistakenly reads as a signal to build bone. In the Phase 3 OPTIMA trial, Pasatru cut new bone lesions by 90% or more versus placebo, which Regeneron says makes it the first FOP treatment to show that benefit in a placebo-controlled trial (Regeneron, 2026). Its label covers adults only.

Zilurgisertib is the third, and it works at a different point from the other 2. It is a small-molecule inhibitor of ALK2 itself, the actual mutated receptor, taken as a pill once a day. Incyte developed it, Mirum licensed worldwide rights in April 2026 for $16 million upfront plus milestones, and the FDA granted the application Priority Review with a target date of September 26th (Mirum, 2026). The application covers patients 12 and older.

Sohonos (palovarotene), approved 2023

An oral retinoid taken chronically at a low dose, with higher weight-based dosing during flare-ups. Works downstream of the faulty signal. Approved for females 8 and older and males 10 and older.

Pasatru (garetosmab), approved August 2026

An intravenous antibody that traps Activin A before it can reach the mutant receptor. Regeneron calls it the first FOP treatment to show this benefit in a placebo-controlled trial. Approved for adults only.

Atebrioz (zilurgisertib), approved September 2026

A once-daily oral ALK2 inhibitor that blocks the mutated receptor at the source. Approved September 25, 2026 for patients 12 and older based on the PROGRESS study.

What the PROGRESS Study Showed

PROGRESS Cohort 1 enrolled 63 people with FOP, 35 adolescents and 28 adults aged 12 to 64 with a median age of 16, and randomized them evenly to zilurgisertib 100mg once daily or placebo for 24 weeks, followed by an open-label extension in which everyone received the drug. New bone was measured the hard way, by whole-body CT scan.

The results, presented at the Endocrine Society's ENDO 2026 meeting in June, favored zilurgisertib most clearly on the measures that describe how much bone formed. Patients on zilurgisertib developed new lesions totaling 0.003 cubic centimeters on average. The placebo group's average was 6.57, a difference of more than 99%. The volume of total new bone, the measure the FDA later used as the basis for approval, fell by 3.2 cubic centimeters on the drug while growing by 24.6 cubic centimeters on placebo (FDA, September 25, 2026). Flare-ups ran at roughly half the placebo rate, 2.34 versus 4.55 a year on average, a result the companies reported without a significance test. In the extension period through Week 48, not a single new lesion appeared in any of the 61 patients with scans, including those who had crossed over from placebo (Mirum and Incyte, 2026).

Incyte chief medical officer Steven Stein called the ENDO results "an important milestone for the zilurgisertib program."

Mirum and Incyte reported that most side effects were mild or moderate and that none led to a dose reduction or to anyone stopping the drug. The FDA label lists the most common side effects as headache, joint pain and upper respiratory infections (22% each), and nosebleeds and nausea (13% each). The label also reports rises in blood iron levels that stayed in the normal range, and it notes that long-term animal cancer studies have not been done.

The Number the FDA Weighed

One complication deserves a plain explanation. In the company's June results, the share of patients who developed any new lesion favored zilurgisertib by 81%, 1 of 32 patients (3.1%) against 5 on placebo (16.7%), but the p-value for that comparison was 0.0986, above the conventional 0.05 bar for statistical significance. With 63 patients and only 6 total events, the result could not rule out chance at the usual bar, which is not proof of benefit or of no benefit. When the FDA approved the drug on September 25th, it based effectiveness on the volume measure instead: the change in total new bone volume over 24 weeks, which Mirum and Incyte say was maintained through week 48 of the extension.

Who Could Take Zilurgisertib and Who Cannot Yet

The approval covers patients 12 years and older, matching PROGRESS Cohort 1. Younger children are not included yet, with 2 additional PROGRESS cohorts still studying children aged 2 to 11, and FOP is usually diagnosed in early childhood, so that gap matters to many families. ClinicalTrials.gov lists the PROGRESS study (NCT05090891) as recruiting, with an age range that starts at 2 years, so families of younger children can ask the study team whether a child qualifies.

“We are pleased to welcome Mirum to the FOP community”

International FOP Association (IFOPA), May 2026

Why 3 Different Mechanisms Matter for One Tiny Disease

A disease with 300 US patients now has a retinoid acting downstream, an antibody trapping the rogue signal, and a pill blocking the broken receptor itself, each with a different route, schedule, age range, and side effect profile. That is not redundancy. Pasatru is approved only for adults, so teenagers 12 and older have Sohonos and Atebrioz as approved choices. An adult who had trouble with retinoid side effects now has other approved options to discuss with a doctor. Nobody yet knows whether any of these can be combined safely, and the field will spend years sorting out sequencing, but choice itself is new here.

“Today marks an important milestone for people living with FOP.”

Chris Peetz, Chief Executive Officer, Mirum Pharmaceuticals, September 25, 2026

In an open letter to the FOP community, Mirum chief executive Chris Peetz wrote that the company shares "a goal of bringing new treatment options to people living with FOP." Atebrioz is now 1 of 4 medicines Mirum sells, alongside Livmarli, Cholbam and Ctexli, so its launch runs through commercial infrastructure the company already has.

What the September 25th Approval Means

The outcome came a day early: approval on September 25th, for patients 12 and older, as a once-daily 100mg dose of 4 tablets sold as Atebrioz. The label is now posted. It sets a continuous 100mg dose once a day rather than dosing tied to flares, says the drug must not be used during pregnancy, and lists drug interactions, including strong CYP3A4 inhibitors and metformin. The PROGRESS extension and pediatric cohorts continue, and children under 12 remain outside the approval for now.

Zilurgisertib's approval came in the middle of the busiest rare disease stretch the FDA has had in years. We cover the full docket in our September decisions guide, and every date is tracked on the FDA decision calendar. The FOP disease page has trial listings and specialist resources for families.