Health Canada has approved a new drug to treat fibrodysplasia ossificans progressiva (FOP), a debilitating condition that leads to formation and accumulation of bone where it does not belong. The drug, palovarotene, was originally identified for this treatment by Maurizio Pacifici, PhD and his team members in the Division of Orthopaedic Surgery at Children’s Hospital of Philadelphia (CHOP). The drug, which will be sold in Canada by Ipsen as Sohonos, targets the pathological process that leads to excess bone and has been approved for use by adults, girls over the age of 8, and boys over the age of 10 with FOP. This is the first-ever approved drug for FOP.
Caused by a genetic mutation, FOP involves a process called heterotopic ossification (HO), which starts with the formation of cartilage that turns into bone in a severe, aggressive, and unrelenting fashion. Starting around the age of 2 or 3, patients with FOP begin to form cartilage and bone at diverse sites outside the skeleton, either spontaneously or after local inflammation, first through the upper body and later, over several years, down the trunk and along the limbs.
The HO bone crowds out muscle and neighboring tissues, which damages and blocks joints and other structures. Eventually it becomes impossible for FOP patients to perform basic life functions, like opening the mouth or using the legs to walk. By the time patients reach their 30s or 40s, very little mobility is usually left. While HO does not occur within internal organs such as the heart or liver, it can cause constriction of the chest wall, impeding normal respiration and circulation. Most patients die prematurely, often from lung and heart complications.
Maurizio Pacifici, PhD, Director of Orthopaedic Research at CHOP, began to explore the possibility of using the retinoic pathway to treat FOP more than 20 years ago, knowing that this mechanism had been shown by his and other labs to regulate cartilage and bone formation. In 2011, Pacifici and his collaborators published a study in Nature Medicine showing that one such retinoid agonist drug, later named palovarotene, was able to inhibit HO formation in an animal model of FOP, with tolerable side effects. In subsequent studies with colleagues at Penn Medicine, the team confirmed that palovarotene also blocked HO in animals carrying the exact human disease-causing mutation for FOP.
“The approval of this drug by Health Canada is a major milestone for patients with FOP, who until now had no approved treatment options for their debilitating condition,” Pacifici said. “This news gives hope to FOP patients and their families, and we look forward to this drug being made available to other patients around the world.”
Ipsen plans to file for approval of the drug in the United States this year. Learn more about this approval here.