FDA Approves Ipsen’s Palovarotene for Ultra-Rare Bone Disease
Pictured: U.S. FDA headquarters in Maryland/iStock, Grandbrothers
Sohonos is an oral medication indicated for the reduction of heterotrophic ossification in adults and children with fibrodysplasia ossificans progressiva (FOP). It is the first medicine authorized by the FDA to treat FOP.
“For the first time, doctors have an approved medicine available to them, shown to reduce the formation of new, abnormal bone growth,” Ipsen R&D head Howard Mayer said in a statement.
Afflicting approximately 400 patients in the U.S. and 900 globally, FOP is an ultra-rare genetic disease in which muscles and connective tissues are gradually replaced by bone. Patients with FOP often suffer from hindered movements and, in cases where joints are affected, lose their mobility. FOP also manifests as breathing problems and difficulties in speaking and eating.
Ipsen’s answer to FOP is Sohonos, an oral small molecule agonist of the gamma subtype of retinoic acid receptors, which are crucial to skeletal development. Sohonos tempers the interaction between the receptors and its ligands, as well as other growth factors and proteins within the retinoid signaling pathway, in turn reducing the abnormal and pathologic extra-skeletal bone formation in FOP.
Sohonos’ label comes with a boxed warning for premature physeal closure in growing pediatric patients and embryo-fetal toxicity. The drug is contraindicated in pregnancy.
The FDA’s approval was backed by data from the Phase III MOVE trial, which according to Ipsen is the first and largest multicenter, open-label study in this space involving both adult and pediatric patients.
In MOVE, Sohonos was able to reduce the annualized heterotrophic ossification by 54% as compared with standard of care without introducing new and uncharacterized safety signals. The most common treatment-emergent adverse events were dry skin and lips, rashes, alopecia and pruritus, and Sohonos’ toxicity profile was consistent with that of other systemic retinoids.
Wednesday’s approval is also the culmination of a long and often bumpy road for Ipsen’s FOP drug. The biotech first tried for an approval in 2021 but voluntarily withdrew its application in August of the same year after the FDA asked for more data during a meeting.
Ipsen filed a resubmission a few months later, which the FDA rejected in December 2022 and requested additional information regarding the data that the company had already provided. In June 2023, after Ipsen responded to the FDA’s request, an advisory committee voted that the benefits of the FOP treatment outweighed its risks.