The U.S. Food and Drug Administration has issued a partial clinical hold in two studies underway to test palovarotene chronic treatment of fibrodysplasia ossificans progressiva (FOP) and multiple osteochondromas, respectively. The partial clinical hold is aimed at the population in the studies who are under the age of 14 years. The hold is in response to reports of early growth plate closure occurring in some pediatric patients with FOP treated with palovarotene.
The hold means that the current phase II and phase III studies involving children with FOP receiving palovarotene must immediately stop (for those under the age of 14 years) while the FDA assesses the information. The FDA plans to issue further information within the next 30 days.
FOP is rare severely disabling disorder characterized by heterotopic ossification— condition in which bone forms outside of the skeleton (i.e., in muscles, tendons or soft tissue). FOP is caused by a mutation in the ACVR1 gene, resulting in excess signaling in the bone morphogenetic pathway. There is currently no approved treatment for FOP.
Multiple osteochondromas are rare chronic disease in which multiple benign bone tumors (osteochondromas or osteocartilaginous exostoses) develop on bones. multiple osteochondromas are typically diagnosed in early childhood during early growth and development. Children often develop limb deformity and restricted movement as they grow. Surgery is the only treatment option available for this condition.
Palovarotene is a retinoic acid receptor gamma (RAR-γ) agonist that was initially developed by Roche pharmaceuticals, and later by Clementia Pharmaceuticals. Earlier year, Ipsen bought Clementia for $1.04 billion, largely based on the promising palovarotene data.