Palovarotene


Palovarotene is a highly selective retinoic acid receptor gamma agonist that is under investigation as a potential treatment for fibrodysplasia ossificans progressiva, an ultra-rare and severely disabling genetic disease characterized by extra-skeletal bone formation in muscle and soft tissues.
Palovarotene is being developed by Clementia Pharmaceuticals and was granted Fast Track and orphan drug designations by the United States Food and Drug Administration for the treatment of FOP and Orphan Medicinal Product Designation by the European Medicines Agency in 2014. Phase II clinical studies yielded positive results.

History

Palovarotene is a retinoic acid receptor gamma agonist licensed to Clementia Pharmaceuticals from Roche Pharmaceuticals. At Roche, palovarotene was evaluated in more than 800 individuals including healthy volunteers and patients with chronic obstructive pulmonary disease. A one-year trial did not demonstrate a significant benefit on lung density in moderate-to-severe emphysema secondary to severe α-antitrypsin deficiency.
In 2011, animal studies demonstrated that RARγ agonists, including palovarotene, blocked new bone formation in both an injury-induced mouse model of heterotopic ossification and a genetically modified biological mouse model of FOP containing a continuously active ACVR1/ALK2 receptor in a dose-dependent manner. A 2016 study demonstrated that palovarotene also inhibited spontaneous heterotopic ossification, maintained limb mobility and functioning, and restored skeletal growth in FOP mouse models.

Clinical Trials

Phase 2

Clementia Announces Plan to Submit a New Drug Application for Palovarotene for the Treatment of FOP Based on Positive Phase 2 Results.

Phase 3

On the 6th of December 2019, Ipsen issued a partial clinical hold for patients under the age of 14. Due to reports of early fusion of growth plates. Ipsen acquired Clementia in 2019.