In just over a month, the FDA has cleared not one, but two treatments for fibrodysplasia ossificans progressiva (FOP), an ultra-rare genetic condition that causes soft tissues to turn to bone.
Regeneron’s Pasatru earned regulatory clearance in late August, and Friday, Mirum Pharmaceutical’s zilurgisertib, to be marketed as Atebrioz, joined the race. The FDA has granted Mirum’s once-daily oral medication a green light to treat FOP in patients ages 12 and up.
Atebrioz has fallen under Mirum's purview thanks to a licensing deal between the rare disease pharma and Incyte in April. Under the deal, Mirum paid $16 million up front for global commercial rights to the drug, with additional regulatory and sales milestones potentially to follow.
FOP is incredibly rare, affecting roughly 900 patients worldwide and 300 in the United States. The disease progressively turns soft tissues to bone in unpredictable waves. Patients can see significant decreases in mobility overnight, and over time, increasing bone mass restricts mobility, fuses joints, and compresses nerves to cause chronic pain.
Atebrioz works to interrupt that disease process by blocking a receptor called activin receptor-like kinase 2 (ALK2), which is overly active in patients with FOP. By blocking the receptor, Atebrioz stops the downstream signaling that mistakenly initiates bone growth in the muscles and ligaments.
The latest approval marks a tripling of the treatment options available to the FOP community. At the start of the summer, only Ipsen’s 2023-approved Sohonos was on the U.S. market.
In Mirum’s research on the patient landscape over the past five years, “we actually estimate there were more [FOP] patients on clinical studies than on commercial drugs. Which we take as a real statement,” Chris Peetz, Mirum’s CEO, told Fierce in an interview. There is a clear unmet need and “an opportunity for bigger impact.”
The FDA’s approval decision was based on the phase 2 Progress trial. In the study, 63 adults and teens took Atebrioz for 24 weeks. Over that period, one person on Atebrioz formed a new bone growth compared to five on placebo. Because the study population is so small, that 81% decline in ossifications missed statistical significance. But the secondary endpoint, the total size of new bone growths, fell by more than 99% compared to placebo.
When patients on placebo were switched to Atebrioz at week 24, their follow-up scans at week 48 showed no new ossifications, and total ossifications decreased.
Mirum’s Atebrioz and Regeneron’s newly approved Pasatru are now set up for a likely rivalry. The two drugs act on the same signaling pathway, albeit in a different manner: Where Atebrioz blocks the ALK2 receptor, Pasatru blocks the protein that binds to ALK2, known as Activin A.
Regeneron has a head start advantage as well as strong phase 3 data showing Pasatru not only reduces ossification formation and growth, but also significantly reduces the painful flare-ups that proceed bone formation.
Atebrioz, however, enters the race with a potential commercial edge. It’s an oral medication compared to Pastaru, which is given by intravenous infusion. And Atebrioz’s newly approved label includes teens and adults ages 12 and up, compared to Pasatru’s adults-only label.
“We’re stepping into those younger patients, where the urgency to prevent the volume of new ossifications is so present,” Peetz said. “The hope is that by preventing these new ossifications, the volume of them, especially in the younger patients, you preserve mobility…even preserve more of a normal day-to-day life.”
Mirum is working to expand the label to even younger patients, too. The Progress trial has a second cohort of patients younger than 12 expected to read out in time for a supplemental application by next year. Peetz credits Incyte’s thoughtful study design for the speed of the potential label expansion.
Regeneron has also announced plans for a pediatric trial, but so far the company has not released any specific details.
Peetz, meanwhile, said that Mirum is geared up for an October launch of Atebrioz. The Foster City-based pharma already has a rare disease team in place to find and support patients through treatment and expects to set the drug’s list price then.
“It’s a really important medicine to get out there,” Peetz said. “I’m excited that the Mirum team was trusted with it.”