A rare and aggressive type of brain cancer that often becomes fatal a year after its diagnosis in children and young adults now has its first FDA-approved therapy, a once-weekly capsule from Jazz Pharmaceuticals.
Approval of the drug, dordaviprone, covers adults as well as children age 1 and older who have had at least one prior treatment — either surgery or radiation — for the brain cancer called H3 K27M-mutant diffuse midline glioma. Dublin-based Jazz will market its newest oncology product under the brand name Modeyso. The approval announced late Wednesday came ahead of the Aug. 18 target date for a regulatory decision. Jazz said it expects to launch Modeyso in coming weeks.
H3 K27M-mutant diffuse midline glioma is named for the genetic mutation that drives tumor growth in this type of cancer. This malignancy mainly affects the midline structures of the brain and spinal cord — locations that make surgery a risky treatment option. While radiation therapy offers an alternative, it is not curative and introduces other complication risks. According to Jazz, patients with H3 K27M-mutant diffuse midline glioma survive a median of one year after diagnosis and less than six months when the cancer progresses following frontline therapy. An estimated 2,000 patients in the U.S. are affected by this cancer each year.
Modeyso is part of a new class of cancer drugs called imipridones, small molecules that target certain G protein-coupled receptors (GPCRs) and enzymes to cause cancer cell death. Modeyso inhibits a GPCR called dopamine D2 receptor and activates an enzyme called mitochondrial caseinolgyic protease P (ClpP). The drug comes from Durham, North Carolina-based Chimerix, a biotech that Jazz acquired this past spring for $935 million. Chimerix now operates as a Jazz subsidiary.
Chimerix’s regulatory submission for Modeyso was based on data from a Phase 2 program consisting of five open-label clinical trials that enrolled children and adults with recurrent H3 K27M-mutant diffuse midline glioma. The FDA’s decision was based on an integrated efficacy analysis of 50 patients selected from the five studies. The overall response rate to the therapy was 22% and the median duration of response was 10.3 months. Results also showed that among those who responded to Modeyso, 73% maintained a response for at least six months and 27% maintained a response for at least 12 months. The most common adverse events reported in the studies included fatigue, headache, nausea, and muscle pain.
In Jazz’s announcement of the approval, Patrick Wen, director of the Center for Neuro Oncology at the Dana-Farber Cancer Institute and a professor of neurology at Harvard University, said Modesyo represents a major turning point for treating brain cancer.
“For the first time, we have an FDA-approved therapy for patients with recurrent H3 K27M-mutant diffuse midline glioma,” said Wen, an investigator in Modesyo’s clinical trials. “While outcomes remain challenging for many patients, the objective responses observed with dordaviprone, including durable benefit in some patients, represent a meaningful advancement. This therapy was developed with the underlying biology of the tumor in mind and introduces a new treatment option for a population with historically limited choices.”
Chimerix, which started as an antiviral drug developer, entered cancer drug research with the 2021 buyout of imipridone-focused Oncoceutics. Besides the program that became Modeyso, the deal included two other imipridone drug candidates: ONC206 is in development for cancers of the central nervous system and ONC212 is a potential treatment for pancreatic cancer and leukemia. Shareholders of Oncoceutics are eligible to receive up to $360 million in milestone payments tied to the progress of all three programs, plus royalties from sales of approved therapies.
The regulatory decision for Modeyso is an accelerated FDA approval based on the Phase 2 data. Jazz will need to verify the drug’s clinical benefit with data from an ongoing Phase 3 study with a targeted enrollment of 450 children and adults. The main goals are measuring overall survival and progression-free survival. In addition to serving as the drug’s confirmatory study, this Phase 3 clinical trial could also support expansion of Modeyso to first-line treatment of H3 K27M-mutant diffuse glioma.
Jazz specializes in neuroscience and oncology drugs. Modeyso is now Jazz’s sixth approved cancer drug. The company has scheduled an Aug. 27 webcast to discuss the clinical data supporting Modeyso as well as the commercialization strategy for the product.
Image: wildpixel, via Getty Images
