When Ipsen ponied up $1 billion in 2019 to acquire Clementia Pharmaceuticals for its rare disease drug palovarotene, the Paris-based company referred to the asset as “largely de-risked.”
Four years, two clinical trial holds, a complete response letter, a European Commission rejection, a scrapped trial in another indication and multiple safety flags, resubmissions and delays later, Ipsen finally has gotten checkered palovarotene across the FDA finish line.
Wednesday, the U.S. regulator signed off on Sohonos, an oral medication to treat the ultra-rare bone disease fibrodysplasia ossificans progressive (FOP) in females ages 8 and older and males ages 10 and older.
Sohonos is a retinoic acid receptor gamma agonist that curbs progression of the genetic disease by reducing the volume of new, abnormal bone growth.
FOP, which affects roughly 400 people in the U.S., causes loss of mobility, leaving most patients in a wheelchair by age 30 and reducing life expectancy to age 56. Many die from respiratory failure caused by excessive bone formation around the rib cage, Ipsen’s R&D chief Howard Mayer, M.D., said in an interview.
“This is a really important moment in that it actually provides the first therapy available for patients with FOP,” Mayer said.
Paving the way for approval were data from a phase 3 trial that showed Sohonos reduced new bone growth by 54%.
The treatment will carry a boxed warning for children outlining the risk of premature closure of growth plates, which can cause bone deformities and stunted growth. There also is a warning for embryo-fetal toxicity.
Ipsen will charge $624,000 annually for a 5-mg daily dose, the company told Reuters, though dosage will depend on disease severity and the weight of a patient, Mayer said.
The company could eventually face competition in the indication from Regeneron. That company's pipeline drug is set up for an FDA submission next year.
Along with the approval, Ipsen receives a priority review voucher, which it can sell or use to speed the processing of a subsequent FDA application.
Roche developed palovarotene but sold its worldwide rights to Canadian company Clementia in 2013 after the treatment flunked a phase 2 trial in emphysema. The fortunes of palovarotene changed when a phase 2 trial in FOP set it up for an FDA submission in 2019.
But soon after Ipsen acquired Clementia, the FDA put two clinical trials of palovarotene on partial clinical holds because of safety concerns. The situation went from bad to worse in the first quarter of 2020, when an interim analysis found the phase 3 trial in FOP was unlikely to meet its primary endpoint.
Two months later, Ipsen scrapped a pivotal trial in a second, potentially more lucrative indication because the pause in dosing under the clinical hold may have compromised the integrity of the data. Between the setbacks, Ipsen recorded a 669 million euro impairment charge.
But through post hoc analysis in the FOP trial, Ipsen found a potential route to approval. While the new approach won over regulators in Canada in 2022, it got a final thumbs-down in Europe last month.
In October of last year, the FDA was set to assemble an advisory committee to discuss palovarotene but canceled the meeting and asked Ipsen for additional data. Two months later, the regulator rejected Ipsen’s application for approval.
Early this year, Ipsen provided the needed data, and a lengthy June advisory committee meeting produced a 10-4 vote in favor of approval.
“There were many surprises,” Mayer said of Ipsen’s initial struggles with palovarotene. “It’s been an obstacle course. But we really followed the science for the benefit of patients and worked collaboratively with FDA.”