On this week’s episode of The CheckRare Brief, we discuss FDA’s approval of Orzeyful (oveporexton) to treat patients with narcolepsy type 1, CAMP4’s first-in-human clinical trial for patients with SYNGAP1-related disorders, and BioMarin’s termination for their ENPP1 deficiency program following mixed results from their phase 3 clinical trial.
The US Food and Drug Administration (FDA) approved Takeda’s Orzeyful (oveporexton) for narcolepsy type 1 on August 5, 2026. The approval came nearly two months ahead of its September 30th PDUFA date. Oveporexton is an orexin receptor 2 agonist designed to directly target the pathway involved and the underlying biology of narcolepsy. This novel mechanism of action could dramatically change how patients with narcolepsy are managed, giving patients more choices. Plans to dispense the drug via specialty pharmacies following the DEA’s review are underway.
CAMP4 is advancing CMP-002 into a first-in-human phase 1/2 trial for SYNGAP1-related disorder, a genetic condition that causes debilitating autistic-like behaviors, seizures, gastrointestinal problems, and intellectual disabilities. There are currently no treatments approved for this rare condition. CMP-002 is an antisense oligonucleotide that binds to regulatory RNA to increase activity of the SYNGAP1 gene and restore SYNGAP1 protein to normal levels.
This clinical trial is a good example of how the rare disease landscape has changed. Advances in genetic testing and the work of patient advocacy groups helped identify these patients and give a once unknown condition a name. Identifying a patient population is crucial to understanding the natural history of the disease, developing clinical trials, and ultimately attracting investment in treatments.
Finally, BioMarin has terminated the development of enzyme replacement therapy BMN 401 after their phase 3 trial in ENPP1 deficiency failed to meet one of its two co-primary endpoints. ENPP1 deficiency is a genetic disorder that results in a reduction of pyrophosphate, causing rickets or soft bones. While the trial showed the drug improving pyrophosphate levels, improvements in bone health, the clinically relevant measure required by the FDA, were not observed. This failed trial is very disheartening for the ENPP1 community, but will hopefully aid in providing the foundation for more robust clinical trials going forward.
Sources
FDA approves Orzeyful (oveporexton)
SYNGAP 1 Clinical Trial To Begin
EENP1 Clinical Program Terminated
2026 Orphan Drugs: PDUFA Dates and FDA Approvals
https://checkrare.com/2026-orphan-drugs-pdufa-dates-and-fda-approvals/
