FDA nod for Mirum’s Atebrioz makes 3 options for ultra-rare bone disease
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The FDA has approved Mirum Pharmaceuticals' Atebrioz (zilurgisertib) for fibrodysplasia ossificans progressiva, expanding options for the ultra-rare bone disease.
The approval of Mirum Pharmaceuticals’ ALK2 inhibitor for fibrodysplasia ossificans progressiva on Friday adds a third option for patients who had long been without any treatments, joining Regeneron’s recently approved Pasatru and Ipsen’s Sohonos. Mirum Pharmaceuticals notched an FDA approval Friday for zilurgisertib — to be marketed as Atebrioz—for the treatment of an ultra-rare bone-forming disease that for decades had no treatments. Mirum joins Regeneron and Ipsen in the tiny space as it brings a third option to the market in as many years.
Colloquially called “stone man syndrome,” fibrodysplasia ossificans progressiva (FOP) causes bone formation within connective tissue including tendons, ligaments and muscles—known as heterotopic ossification (HO)—leading to pain, stiffness and immobility over time.
“To put it simply, it’s a terrible disease,” Mirum CEO Chris Peetz told BioSpace ahead of the company’s new approval. “Even bumping into something and bruising can result in signaling that turns soft tissue into bone and accumulates over time. Into young adulthood, it can become life-threatening, and before these treatments, there was nothing that could stop progression.” The genetic disorder is estimated to affect one in a million people globally.
FOP specialist Angela Cheung, director of the osteoporosis program at University Health Network in Toronto, described the patient experience. “People get trapped in their own skeleton, like tin soldiers, and they progressively get worse over time with an average life expectancy of 56 years, many even younger.”
Cheung called the 20-year-old discovery of the ACVR1 gene, which causes this abnormal signaling, “groundbreaking,” adding that the knowledge enabled clinicians and researchers to develop therapies for patients with the disease. Ipsen’s Sohonos was the first to market, approved by the FDA in August 2023, then Regeneron’s Pasatru followed just last month.
Mirum’s approval has thus now tripled the available options for patients with FOP in just five weeks’ time. Cheung told BioSpace that in a disease like FOP, patients need options, and that the three drugs available, each of which works in a different way and is “not for everyone,” offer just that.
Atebrioz, approved by the FDA for patients 12 years and older, is a once-daily pill that inhibits the activin receptor-like kinase 2 (ALK2) protein, which has been found to cause abnormal bone growth in FOP. Originally discovered by Novartis and later licensed by Incyte for clinical development, rare disease–focused Mirum gained full ownership of Atebrioz in April.
Friday’s approval was based on data from Cohort 1 of the Phase 2 PROGRESS study, in which treatment with Atebrioz elicited an 81% reduction in new lesion volume and a 99% reduction in total volume compared with placebo at 24 weeks, meeting the primary endpoint. These treatment effects were maintained through week 48 of an open-label-extension study, according to a press release issued by Mirum and Incyte on Friday.
The drug was generally well tolerated, the companies said, with only mild or moderate side effects, including headache, joint pain, respiratory infection, nosebleed and nausea. There were no adverse events that led to treatment discontinuation or dose reduction.
