Rare and aggressive brain cancers that affect children receive FDA-approved drugs
A rare and aggressive type of brain cancer that is often fatal after diagnosis in children and young people, is now an FDA-approved therapy, a once-weekly capsule by Jazz Pharmaceuticals.
The drug approval, dordaviprone covers adults and children aged 1 and over who have previously treated at least one (surgical or radiation) called H3 K27M mutation diffuse midline glioma. Dublin-based Jazz will sell its latest oncology products under the Modeyso brand. The approval announced late Wednesday is subject to regulatory decisions ahead of the target date of August 18. The Jazz said Modeyso is expected to be launched in the coming weeks.
The diffuse midline glioma with the H3 K27M mutation is named after the genetic mutation of this cancer. This malignant tumor mainly affects the midline structure of the brain and spinal cord, making surgery a dangerous treatment option. While radiation therapy provides an alternative, it does not cure and introduces other complication risks. According to Jazz, patients with H3 K27M mutations survived a median year after diagnosis, while cancer progressed less than six months after first-line treatment. An estimated 2,000 U.S. patients are affected by this cancer each year.
Modeyso is part of a new cancer drug called acetylate, a drug targeting small molecules and enzymes that target certain G protein-coupled receptors (GPCRs) that cause cancer cell death. Modeyso inhibits GPCR called the dopamine D2 receptor and activates an enzyme called mitochondrial casein protease P (CLPP). The drug comes from Chimerix, North Carolina-based, a jazz music that was acquired last spring for $935 million. Chimerix is now a Jazz subsidiary.
Chimerix's regulatory submission to Modeyso is based on data from the Phase 2 program, which consists of five open-label clinical trials that recruit children and adults with H3 K27M Mutant diffuse midline glioma. The FDA's decision was based on a comprehensive efficacy analysis of 50 patients selected from five studies. The overall response rate to treatment was 22%, and the median response duration was 10.3 months. The results also show that among those who responded to Modeyso, 73% maintained a response for at least six months, while 27% maintained a response for at least 12 months. The most common adverse events reported in the study include fatigue, headache, nausea, and muscle pain.
In the process of announcing the approval of jazz, Patrick Wen, director of the Center for Neuro-Oncology at the Dana-Farber Cancer Institute, a professor of neurology at Harvard University, said Modesyo was the main turning point in the treatment of brain cancer.
“This is the first time we have provided FDA-approved therapy for patients with diffuse midline glioma with recurrent H3 K27M mutations,” said Wen, a researcher at the Modesyo clinical trial. “Although the results remain challenging for many patients, the objective responses observed with dordaviprone, including the lasting benefits of some patients, represent meaningful advances. This therapy has been developed in the basic biology of brain tumors and has introduced a new treatment for the population that has historically limited options.”
Chimerix started as an antiviral drug developer who conducted cancer drug research with Onceceutics, acetone-focused in 2021. In addition to becoming Modeyso's plan, the deal includes two other meridone candidates: cancer in the central nervous system is developing ONC206, ONC212, a potential treatment for pancreatic cancer and leukemia. Oncoutics shareholders are eligible for milestone payments of up to $360 million associated with the progress of all three programs and receive sales royalties for approved therapies.
Modeyso's regulatory decision is based on accelerated FDA approval of phase 2 data. Jazz will need to verify the clinical benefit of the drug through data from an ongoing phase 3 study, with targeted enrollment rates for 450 children and adults. The main goal is to measure overall survival and progress-free survival. In addition to being a confirmatory study of the drug, this phase 3 clinical trial could support the extension of Modeyso to the first-line treatment of diffuse gliomas with H3 K27M mutations.
Jazz specializes in neuroscience and oncology drugs. Modeyso is now the sixth recognized cancer drug for jazz. The company has scheduled a webcast on August 27 to discuss clinical data supporting Modeyso and its commercialization strategies.
Image: Wildpixel, by Getty Images
