Jazz Pharmaceuticals has announced that the US Food and Drug Administration (FDA) has granted accelerated approval for Modeyso (dordaviprone) for the treatment of adult and pediatric patients 1 year of age and older with H3 K27M-mutant diffuse midline glioma – a rare and highly aggressive brain tumour – with progressive disease following prior therapy.

Continued approval for this indication may depend on verification and description of clinical benefit in the Phase 3 ACTION confirmatory trial, the Irish global biopharma company said.

Modeyso is the first and only treatment option approved by the FDA for this ultra-rare and aggressive brain tumour that affects an estimated 2,000 people in the US each year, many of whom are children and young adults.

The disease is characterised by rapid progression and historically has had no effective systemic treatment options. In response to this critical unmet need, Modeyso is expected to become commercially available in the coming weeks.

"This is a major turning point in neuro-oncology," said Patrick Wen, Director, Center for Neuro-Oncology, Dana-Farber Cancer Institute and Professor of Neurology, 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. 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,” he added.

Modeyso is administered as an oral capsule once weekly.

The FDA’s decision was supported by an integrated efficacy analysis of 50 patients with recurrent H3 K27M-mutant diffuse midline glioma, drawn from five open-label clinical studies based on predefined eligibility criteria. The overall response rate (ORR), as assessed by blinded independent central review (BICR) using Response Assessment in Neuro-Oncology (RANO) 2.0 criteria, was 22 percent, with an additional responder identified by integrated RANO 2.0. Among responders, the median duration of response was 10.3 months, with 73 percent maintaining their response for at least six months and 27 percent for at least 12 months.

"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," added Joshua E. Allen, Chief Scientific Officer, Chimerix, a Jazz Pharmaceuticals Company.

H3 K27M-mutant diffuse midline glioma primarily affects the midline structures of the brain and spinal cord. It is characterised by a specific genetic mutation (H3 K27M) that disrupts epigenetic regulation and drives tumour growth. Most commonly diagnosed in children and young adults, patients with this type of glioma often face an extremely poor prognosis, with limited therapeutic options and very low survival rates following recurrence. Median survival is approximately one year from diagnosis and less than six months after progressing following frontline therapy.

Modeyso (dordaviprone) is a protease activator of the mitochondrial caseinolytic protease P (ClpP) and also inhibits dopamine D2 receptor (DRD2). In vitro, dordaviprone activates the integrated stress response, induces apoptosis, and alters mitochondrial metabolism, leading to restored histone H3 K27 trimethylation in H3 K27M-mutant diffuse glioma.

Headquartered in Dublin, Ireland, Jazz is focused on developing potentially life-changing medicines for people with serious diseases – often with limited or no therapeutic options. With research and development laboratories and manufacturing facilities in multiple countries, it has a diverse portfolio of marketed medicines, including leading therapies for sleep disorders and epilepsy, and a growing portfolio of cancer treatments.