|Chemical and physical data|
|Molar mass||414.5393 g/mol|
|3D model (Jmol)||Interactive image|
Palovarotene is a highly selective retinoic acid receptor gamma (RAR-γ) agonist that is under investigation as a potential treatment for fibrodysplasia ossificans progressiva (FOP), an ultra-rare and severely disabling genetic disease characterized by extra-skeletal bone formation (heterotopic ossification or HO) 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 (EMA) in 2014. Phase II clinical studies are currently underway.
Palovarotene is a retinoic acid receptor gamma (RARγ) 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 (COPD). A one-year trial did not demonstrate a significant benefit on lung density in moderate-to-severe emphysema secondary to severe α(1)-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 (HO) 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.
Palovarotene is currently being investigated as a potential therapy for FOP, a disorder of heterotopic ossification, in humans. Palovarotene began phase 2 clinical trials for human testing in October 2016.
Currently phase 3 is beginning clinical trials at LA biomed.
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