FDA Accepts NDA for Low-Sodium Oxybate TRN-257 in Narcolepsy and Idiopathic Hypersomnia

According to a new announcement, the FDA has accepted Tris Pharma’s new drug application (NDA) for TRN-257 for the treatment of cataplexy or excessive daytime sleepiness in adults with narcolepsy, as well as excessive daytime sleepiness in adults with idiopathic hypersomnia, with a PDUFA date set for June 20, 2026.¹ The agent incorporates 2 of the company’s proprietary technology platforms, RaftWorks and LiquiXR, to achieve a controlled-release profile and support a once-nightly, low-sodium dosing regimen.

"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," Maurice M. Ohayon, MD, DSc, PhD, professor and director of the Stanford Sleep Epidemiology Research Center at Stanford University, said in a statement.¹ "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."

The NDA submission is supported by data from multiple pharmacokinetic and safety studies and incorporates Model-Informed Drug Development-based approaches to showcase the efficacy and safety of TRN-257. According to Tris Pharma, the submission also references the agency's prior safety and efficacy findings for currently marketed oxybate products. In addition, it includes a comprehensive Human Factors Engineering and Usability Engineering study report, which demonstrated that representative patients were generally able to perform tasks and use TRN-257 as intended when following the proposed labeling.

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“The FDA’s acceptance of our NDA for TRN-257 reflects Tris Pharma's commitment to solving complex therapeutic challenges,” Ketan Mehta, founder and chief executive officer at Tris Pharma, said in a statement.¹ “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.”

TRN-257’s design seeks to address two main drawbacks of traditional sodium oxybates:

• Lower sodium burden: significantly reduces daily sodium intake compared to high-sodium oxybate therapies — potentially lowering long-term cardiovascular risk.
• Once-nightly dosing: eliminates the need to wake up for a second dose, making therapy more convenient and potentially improving sleep consolidation and adherence.

Traditional sodium oxybate (e.g., Xyrem) has been used since about 2002 to treat narcolepsy — particularly cataplexy and excessive daytime sleepiness. Findings from a recent meta-analysis of randomized controlled trials published in Sleep and Breathing reinforced the efficacy of sodium oxybate, which has been FDA-approved for several years, for patients living with the sleep disorder, particularly in managing cataplexy and improving daytime wakefulness.²

In the analysis, treatment with sodium oxybate resulted in a significant reduction in weekly cataplexy attacks compared with placebo (mean difference [MD] = -5.04; 95% CI, -6.35 to -3.72; P <.00001). Measures of wakefulness and sleepiness also improved, with notable gains observed in the Maintenance of Wakefulness Test (MD = 4.66; 95% CI, 2.24 to 7.07; P =.0002) and Epworth Sleepiness Scale (ESS) scores (MD = -1.93; 95% CI, -2.73 to -1.13; P <.00001). Global clinical improvement, measured by the Clinical Global Impression-Improvement (CGI-I) scale, was more than twice as likely reported in sodium oxybate-treated patients (risk ratio [RR] = 2.15; 95% CI, 1.69 to 2.73; P <.00001).

REFERENCES
1. Tris Pharma Announces FDA Acceptance of NDA for Once-Nightly, Low-Sodium Oxybate Product for Narcolepsy and Idiopathic Hypersomnia. News release. Tris Pharma. December 9, 2025. Accessed December 9, 2025. https://www.trispharma.com/tris-pharma-announces-fda-acceptance-nda-oxybate-narcolepsy/
2. Amin AM, Hassan A, Khlidj Y, et al. Efficacy and safety of sodium oxybate treatment in adults with narcolepsy and cataplexy: a systematic review and meta-analysis. Sleep Breath. 2024;29(1):12. Published 2024 Nov 27. doi:10.1007/s11325-024-03163-5