The FDA is expected to issue a decision by June 20, 2026 on TRN-257, a once-nightly, controlled-release formulation of sodium oxybate developed by Tris Pharma for adults with narcolepsy and idiopathic hypersomnia. If approved, it would become the lowest-sodium oxybate on the market and the only version that does not require patients to wake up in the middle of the night for a second dose.
The Sodium Problem
Sodium oxybate has been a cornerstone of narcolepsy treatment for over two decades. Sold as Xyrem since 2002, it remains one of the most effective drugs for reducing cataplexy attacks and excessive daytime sleepiness. But it comes with a significant drawback: at the maximum recommended 9-gram nightly dose, Xyrem delivers approximately 1,640 mg of sodium — nearly 70% of the American Heart Association's recommended daily limit of 2,300 mg, consumed in a single medication.
For patients with narcolepsy who also have hypertension, heart failure, or kidney disease — conditions that require strict sodium restriction — this has been a serious clinical concern. A lower-sodium alternative, Xywav, was approved in 2020 and reduced the sodium content to 131 mg at the same dose, a 92% reduction. But even Xywav still requires twice-nightly dosing.
TRN-257 pushes both numbers further. Its sodium content is just 80 mg at a 9-gram dose — roughly 95% less than Xyrem and 39% less than Xywav. And its controlled-release technology eliminates the need for a second dose entirely.
How It Works
The drug uses two proprietary technology platforms developed by Tris Pharma: RaftWorks and LiquiXR. Together, these create a controlled-release profile that sustains therapeutic blood levels of sodium oxybate through the night from a single bedtime dose.
This is a meaningful practical advance. Current oxybate regimens require patients to take one dose at bedtime and set an alarm to wake up 2.5 to 4 hours later for a second dose — a routine that fragments the very sleep the medication is supposed to improve. Many patients and their physicians consider the middle-of-the-night dosing to be the most burdensome aspect of oxybate therapy.
The Regulatory Path
Tris Pharma submitted a 505(b)(2) New Drug Application — a regulatory pathway that allows a company to rely partly on the FDA's existing safety and efficacy findings for previously approved drugs. The submission is supported by multiple pharmacokinetic and safety studies and incorporates Model Informed Drug Development (MIDD) approaches to bridge efficacy data from currently marketed oxybate products.
The FDA accepted the application in December 2025 and set a Prescription Drug User Fee Act (PDUFA) target action date of June 20, 2026.
A Crowded but Differentiated Field
The narcolepsy treatment landscape has expanded considerably in recent years. Xywav addressed the sodium problem; Lumryz (approved 2023) introduced an extended-release, once-nightly oxybate but with a higher sodium load. And an entirely different class of drugs — orexin receptor agonists like Takeda's oveporexton — is approaching FDA review with a mechanism that targets the underlying neurotransmitter deficit in narcolepsy type 1.
TRN-257 does not represent a new mechanism. It is the same active ingredient that has been used for decades. What it offers is a practical refinement: the lowest sodium content, the simplest dosing regimen, and potentially the lowest barrier to long-term adherence among the available oxybate options.
What This Means for Patients
Narcolepsy affects an estimated 200,000 Americans, though the majority remain undiagnosed. For those who are diagnosed and treated with oxybate, the middle-of-the-night second dose is a persistent source of frustration and nonadherence. A once-nightly, ultra-low-sodium alternative could meaningfully improve quality of life — particularly for patients who also manage cardiovascular or renal conditions that make high-sodium medications risky.
The June 20 PDUFA date means patients and clinicians should have clarity within days on whether TRN-257 will join the available treatment options. If approved, it would give prescribers a third generation of oxybate that addresses the two most common complaints about the drug class: too much sodium, and too many doses.
