FDA Accepts NDA for TRN-257, First Once-Nightly Low-Sodium Oxybate for Narcolepsy and Idiopathic Hypersomnia
Key Insights
The FDA has accepted Tris Pharma's New Drug Application for TRN-257, a controlled-release, low-sodium oxybate product for treating narcolepsy (search) and idiopathic hypersomnia (search) in adults.
TRN-257 represents the lowest sodium oxybate treatment currently in development, containing only 80 mg sodium per 9g dose with once-nightly dosing.
The drug combines Tris Pharma's proprietary RaftWorks and LiquiXR technologies to eliminate the need for disruptive twice-nightly dosing while reducing cardiovascular risks.
Tris Pharma announced that the US Food and Drug Administration has accepted the New Drug Application for TRN-257, a controlled-release, low-sodium oxybate product designed to treat cataplexy (search) or excessive daytime sleepiness (search) in adults with narcolepsy (search) and idiopathic hypersomnia (search) in adults. The FDA has set a Prescription Drug User Fee Act goal date of June 20, 2026.
Addressing Critical Treatment Limitations
TRN-257 represents a significant advancement in sleep disorder therapeutics as the lowest sodium oxybate treatment currently in development, containing only 80 mg sodium for a 9g dose with once-nightly administration. This formulation addresses two major limitations of existing oxybate treatments: high sodium content that poses cardiovascular risks and disruptive twice-nightly dosing that interrupts sleep.
"Currently, patients face a difficult trade-off with existing treatments that either burden them with high sodium levels, posing significant cardiovascular risks, or require disruptive twice-nightly dosing that interrupts sleep, that otherwise is intended to induce sleep," said Maurice M. Ohayon, MD, DSc, PhD, Professor and Director of the Stanford Sleep Epidemiology Research Center at Stanford University. "As the first oxybate formulation to combine a convenient once-nightly regimen with the lowest sodium content, TRN-257 is uniquely designed to eliminate this compromise."
Innovative Drug Delivery Technology
TRN-257 was developed by combining two of Tris Pharma's proprietary technologies: RaftWorks™ and LiquiXR®. The RaftWorks technology enables sustained, controlled release and absorption of drugs that have a narrow window of absorption, slowly and continuously releasing drug from the raft to enable absorption in the upper gastrointestinal tract. Meanwhile, LiquiXR is a particle-based technology that combines principles of ionic chemistry and controlled release science to enable delivery in oral liquid and solid dosage forms while maintaining benefits of immediate release.
Regulatory Pathway and Supporting Data
The 505(b)(2) NDA submission is supported by data from multiple pharmacokinetic and safety studies and involves Model Informed Drug Development-based approaches to demonstrate efficacy and safety of TRN-257. The submission includes the FDA's previous safety and efficacy findings from currently-marketed oxybate products as well as a comprehensive Human Factors Engineering and Usability Engineering study report.
The HFE/UE validation study demonstrated the ease of use of TRN-257, with representative patients generally able to perform critical tasks and use TRN-257 as intended when following the proposed labeling.
Clinical Significance for Sleep Disorders
Narcolepsy (search) affects an estimated 1 in 2,000 individuals in the U.S., representing over 200,000 Americans, and is characterized by excessive daytime sleepiness (search) and cataplexy (search). Idiopathic hypersomnia (search) is a separate, rare disorder estimated to affect tens of thousands of diagnosed adults in the U.S. and is characterized by chronic, disabling excessive daytime sleepiness.
Patients with these conditions suffer from profound fatigue, impaired quality of life, and an increased risk of serious cardiovascular comorbidities. The need for low-sodium treatment options in this population is critical due to the potential for existing high-sodium oxybates to exacerbate hypertension (search) and other cardiovascular risks.
"The FDA's acceptance of our NDA for TRN-257 reflects Tris Pharma's commitment to solving complex therapeutic challenges," said Ketan Mehta, Founder and Chief Executive Officer of Tris Pharma. "The unique formulation design developed by Tris scientists—using our innovative RaftWorks and LiquiXR platforms—achieves drug delivery capabilities that are expected to redefine the patient experience, potentially offering a life-changing improvement in how they manage their condition and protect their long-term health."