Background: Fibrodysplasia Ossificans Progressiva (FOP) is an invalidating disorder marked by severe heterotopic ossifications (HO), causing diffuse ankylosis and early death. Currently there is no approved treatment for FOP in the world except in the USA and Canada. AZD0530 (saracatinib), originally designed for ovarian cancer treatment, was identified by our team as a potent inhibitor of the ALK2-kinase which, through R206H mutation of the ACRV¹-gene, causes this rare bone disease. The purpose of this study is to investigate the repositioning of AZD0530 to treat patients with FOP after it proved effective in preventing HO in FOP mouse models. This study is funded by the Innovative Medicines Initiative and supported by IFOPA.

Methods: The Saracatinib Trial to Prevent FOP (STOPFOP) is a phase 2a, double blinded multicentre trial, wherein patients are randomized to receive 6 months AZD0530 or placebo, followed by 12 month open-label phase comparing AZD0530 treatment with control data from a previous trial. Although the COVID pandemic resulted in study delays we continue to include 16 FOP patients, aged 18-65 years, with the classic FOP mutation (R206H). Endpoints are objective change in heterotopic bone volume as measured by low-dose whole-body computer tomography, [18F] NaF PET activity and patient reported outcome measures such as the FOP-IADL questionnaire.

Discussion: Drug repositioning is especially useful in rare diseases with limited study populations, such as FOP. It represents an ideal solution for limiting risks in early clinical studies and existing pre-clinical and clinical knowledge may also allow more affordable pricing once an indication is approved.

With positive study outcome, AZD0530 may provide a rapidly translatable therapy for FOP due to the availability of extensive safety data from over 600 patients in more than 28 registered clinical trials using AZD0530. At the time of writing, 17 patients are included and 11 hav