Introduction to dordaviprone-Modeyso: what is it a medicine for?

Dordaviprone - Modeyso is a protease activator specifically indicated for the treatment of diffuse midline glioma in adult and pediatric patients 1 year of age and older, specifically those with the H3 K27M mutation and whose disease has progressed after prior therapy. Gliomas originate from glial cells in the central nervous system, and the H3 K27M mutation is a specific mutation in the gene encoding histone H3 that is commonly found in most diffuse midline gliomas, especially tumors located in important regions such as the brainstem and thalamus.

The active ingredient in Modeyso, dordaviprone, is an activator of mitochondrial caseinolytic protease P (ClpP) and also inhibits dopamine D2 receptor (DRD2). In in vitro studies, dordaviprone was able to activate integrated stress responses, induce apoptosis, alter mitochondrial metabolism, and restore the K27 trimethylation status of histone H3 in H3 K27M mutant diffuse gliomas.

Modeyso's accelerated FDA approval was based on a comprehensive efficacy analysis of 50 patients with recurrent H3 K27M-mutant diffuse midline glioma who participated in five open-label clinical studies (ONC006, ONC013, ONC014, ONC016 and ONC018). Subsequent approval will be subject to validation of the safety and clinical benefit of Modeyso in an ongoing Phase 3 clinical trial (NCT05580562) in patients with newly diagnosed H3 K27M mutated diffuse glioma after radiation therapy.

Currently, Modeyso is administered orally once a week on an empty stomach (at least 1 hour before or 3 hours after eating) until disease progression or unacceptable toxicity occurs. Common adverse reactions include fatigue, headache, vomiting, nausea, and musculoskeletal pain. On laboratory testing, common grade 3 or 4 abnormalities include lymphopenia, decreased calcium, and increased alanine aminotransferase.

Reference materials:https://www.drugs.com/history/modeyso.html