Zilurgisertib for the treatment fibrodysplasia ossificans progressiva

Zilurgisertib is in development for the treatment of patients with fibrodysplasia ossificans progressiva (FOP). FOP is an ultra-rare disease which results in development of abnormal bone in muscles, tendons, and ligaments where bone would not normally be present, this is known as heterotopic ossification (HO). FOP is caused by spontaneous mutations within the gene that codes for a protein called Activin a Receptor type I (ACVR1), which is responsible for regulating muscle and bone growth. Mutations in this gene result in over-activation of ACVR1 which in turn causes the overgrowth of bone and cartilage seen in the disease. As the disease progresses, patients with FOP experience increasingly limited mobility due to progressive bone formation.
This results in wheelchair use, usually by the second decade of life, respiratory complications and eventually death. Current treatment options for patients with FOP are limited to managing the risk of soft-tissue injury and symptom relief, so there is a need for additional treatment options that target the underlying cause of the disease.