Chimerix is seeking accelerated approval from the U.S. Food and Drug Administration (FDA) for dordaviprone, a novel small molecule imipridone, for the treatment of patients with recurrent H3 K27M-mutant diffuse glioma. The company has submitted a New Drug Application (NDA) supported by positive Phase 2 clinical data and is requesting Priority Review, which, if granted, could lead to a decision in the third quarter of 2025.
H3 K27M-mutant gliomas are aggressive tumors that occur in both children and adults, impacting over 2,000 patients annually in the United States. These gliomas are characterized by a mutation in the H3 K27M gene, leading to a loss of H3K27 trimethylation, a critical epigenetic modification. Currently, there are limited treatment options available, highlighting a significant unmet medical need.
Clinical Efficacy and Safety Data
The NDA submission is based on the objective response rate (ORR) observed in a Phase 2 clinical trial involving 50 patients. Dordaviprone demonstrated an ORR of 28%, as assessed by blinded independent central review using the Response Assessment in Neuro-Oncology (RANO) 2.0 criteria. The median duration of response was 10.4 months, and the median time to response was 4.6 months. These data suggest that dordaviprone has the potential to provide meaningful clinical benefit to patients with this aggressive form of glioma.
In addition to efficacy data, the NDA includes a comprehensive safety database from glioma patients and healthy volunteers, supporting a favorable benefit/risk profile. Dordaviprone has also demonstrated the ability to reverse H3K27 trimethyl loss, the central hallmark of H3 K27M-mutant glioma, in both clinical and nonclinical studies.
Regulatory Pathway and Market Potential
Chimerix has requested that the FDA grant Priority Review to the dordaviprone NDA. If granted, the review period would be reduced to six months from the standard ten months, potentially leading to approval in the third quarter of 2025. Dordaviprone has already received Rare Pediatric Disease Designation for H3 K27M-mutant glioma, making Chimerix eligible for a Rare Pediatric Disease Priority Review Voucher, which can be used to expedite the review of another drug or sold to another company.
"In anticipation of a potential approval, we have bolstered our commercial leadership team and will be ready for a U.S. launch as early as the third quarter of 2025, pending application acceptance and Priority Review, if granted," said Mike Andriole, CEO of Chimerix. If approved, dordaviprone would be the first FDA-approved treatment for H3 K27M-mutant glioma and among the first molecularly targeted therapies for high-grade gliomas.
