CHOP Researchers Develop First Drug Treatment Approved for Severe Bone Disease

The first approved drug treatment for FOP, palovarotene, was discovered and developed in the Pacifici Laboratory at CHOP.

mccannn [at] chop.edu (By Nancy McCann)

Canada is the first country worldwide to approve the use of palovarotene (Sohonos) as a treatment against heterotopic ossification (HO) in adults and children with fibrodysplasia ossificans progressiva (FOP), a debilitating, ultra-rare and often fatal disease. The Pacifici Laboratory at Children's Hospital of Philadelphia discovered and developed the treatment. Palovarotene is a retinoid agonist drug manufactured by the pharmaceutical company Ipsen and is approved for females who are 8 years old and older, and for males who are 10 years old and older.

HO is the formation of excess skeletal tissue at abnormal anatomical locations — outside the skeleton —and is caused by a genetic mutation in patients with FOP. Starting at the age of 2 or 3 in these children, HO begins through the upper body and then develops down the torso and along the limbs, forming either spontaneously or after local inflammation. Once the bone forms, it is irreversible and leads to loss of mobility, severe health complications and shortened life expectancy.

Dr. Pacifici's Research Reveals Pathway to Treatment

Maurizio Pacifici, PhD

Maurizio Pacifici, PhD, director of Research in the Department of Orthopaedic Surgery at CHOP, has been studying the use of the retinoic pathway to treat FOP for more than 20 years, as his lab and others had shown this mechanism to regulate cartilage and bone formation. If his lab could identify a clinically suitable pharmacologic compound that would turn this pathway on, Dr. Pacifici hypothesized they could use it to turn off the development of unwanted cartilage and bone in FOP patients.

After demonstrating that one such retinoid agonist drug known as R667, or palovarotene, was able to inhibit HO formation in an animal model of FOP with tolerable side effects, Dr. Pacifici and his collaborators published their findings in Nature Medicine. Subsequent studies with colleagues at the University of Pennsylvania showed that palovarotene also blocked HO in animals carrying the exact human disease-causing mutation for FOP. Clinical trials followed, including positive results from the MOVE trial, the first global multicenter Phase III trial in FOP. The trial findings demonstrated a 62 percent reduction in mean annualized new HO volume in participants treated with palovarotene.

"The dream of every biomedical researcher is to go from the lab to the bedside and discover a treatment that improves the lives of patients," Dr. Pacifici said. "We are very excited that Health Canada approved this drug and look forward to other countries doing the same, as the patients currently lack an effective treatment that will slow down or block their debilitating disease."

Ipsen plans to file for approval of the drug in the United States later this year and is in discussions with other regulatory authorities around the world.

For more information see CHOP News.