Modeyso becomes 1st FDA-approved treatment for rare glioma
Accelerated approval applies to diffuse midline glioma with H3 K27M mutation
Jazz Pharmaceuticals said the U.S. Food and Drug Administration (FDA) granted accelerated approval to the weekly oral therapy dordaviprone, to be marketed under the brand name Modeyso. According to the company and the FDA, the drug is the first approved treatment for a rare and aggressive form of glioma.
The approval covers Modeyso’s use in adults and children ages 1 and older who have diffuse midline glioma harboring an H3 K27M mutation, with disease that continues to progress following earlier lines of therapy. According to Jazz, this rare form of the disease affects roughly 2,000 people in the U.S. each year.
Jazz acquired Modeyso’s original developer, Chimerix, earlier this year. Chimerix submitted an application to the FDA requesting the accelerated approval of Modeyso late last year, and the agency granted it priority review, shortening the typical review time.
“The FDA approval of Modeyso is a milestone moment for the patients and families who have long needed new options, the clinicians who have tirelessly searched for solutions, and the researchers and advocates who never gave up,” Joshua E. Allen, PhD, chief scientific officer of Chimerix, said in a press release from Jazz. “This approval not only equips clinicians with the first targeted option for this disease but also signals a meaningful shift in what patients and families can expect after diagnosis.”
Accelerated approval is a type of conditional approval that the FDA can give to treatments that have shown promising signs of clinical benefit in clinical trials. Therapies granted accelerated approval are allowed to be brought to market on the condition that developers conduct additional trials to confirm the clinical benefit of the treatment and future approval is contingent upon those data.
Continued approval may rest on trial data
Jazz said Modeyso’s full approval may be contingent on data from an ongoing Phase 3 trial, ACTION (NCT05580562), which is assessing the safety and clinical benefit of the therapy in newly diagnosed patients with H3 K27M-mutant diffuse glioma who have received frontline radiotherapy.
The FDA’s decision to grant accelerated approval to Modeyso was based on data from 50 adults and children with recurrent H3 K27M-mutant diffuse midline glioma who were treated with the therapy in one of five open-label clinical trials: ONC006 (NCT02525692), ONC013 (NCT03295396), ONC014 (NCT03416530), ONC016 (NCT05392374), and ONC018 (NCT03134131).
Findings showed that 11 of the patients, or 22%, had an overall objective response, essentially meaning a reduction in tumor growth. The median duration of response was 10.3 months, and the response lasted at least six months in most patients.
“This is a major turning point in neuro-oncology,” said Patrick Wen, MD, director of the Center for Neuro-Oncology at Dana-Farber Cancer Institute and a neurology professor at Harvard Medical School. “For the first time, we have an FDA-approved therapy for patients with recurrent H3 K27M-mutant diffuse midline glioma. While outcomes remain challenging for many patients, the objective responses observed with dordaviprone, including durable benefit in some patients, represent a meaningful advancement.”
The H3 K27M mutation in glioma cells alters the way DNA is physically packaged within cells, disrupting their normal genetic activity. This is ultimately thought to help drive cancer growth.
Modeyso is an oral small molecule designed to interfere with processes cancer cells use to survive and multiply. Laboratory experiments have shown that Modeyso can help normalize DNA packaging inside cells harboring the H3 K27M mutation, making it a promising therapy for patients with gliomas containing this mutation.
“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,” Wen said.
According to the therapy’s prescribing information, the most common side effects of Modeyso include fatigue, headache, vomiting, nausea, and musculoskeletal pain. The most common serious side effects include low immune cell counts, low calcium levels, and elevated levels of liver enzymes (a potential sign of liver damage). Data from more than 370 patients showed that about one in three patients experiences serious side effects, according to Jazz.
David F. Arons, president and CEO of the National Brain Tumor Society, said H3 K27M-mutant diffuse midline glioma “is a fast-moving, devastating disease that turns families’ lives upside down.”
“For years, this diagnosis has lacked an approved treatment and today, that changes,” Arons said. “Families finally have a treatment option, and a reason to believe in more time together to make memories that might not have otherwise been possible.”
About the Author
