The Quest for Unbroken Sleep: A New Drug Aims to End a Painful Trade-Off

MONMOUTH JUNCTION, NJ – December 09, 2025 – For hundreds of thousands of Americans living with the chronic neurological disorders narcolepsy and idiopathic hypersomnia (IH), the night offers little respite. Instead, it presents a difficult choice, a frustrating trade-off between effective treatment and the very thing they crave most: uninterrupted sleep. Now, a development from biopharmaceutical company Tris Pharma may signal a turning point. The U.S. Food and Drug Administration (FDA) has accepted the company’s New Drug Application (NDA) for TRN-257, a novel formulation designed to tackle this long-standing dilemma head-on.

TRN-257 is an investigational oxybate product, a class of medication known to be highly effective for treating the debilitating excessive daytime sleepiness (EDS) and cataplexy (sudden loss of muscle tone) that characterize these conditions. Yet, its true innovation lies not in what it is, but how it works. By combining a convenient once-nightly dose with the lowest sodium content of any oxybate therapy, it aims to eliminate what one expert calls a “difficult trade-off” for patients who currently must choose between cardiovascular risk and a sleep cycle shattered by middle-of-the-night dosing.

The Human Cost of a Broken Night

To understand the significance of this development, one must first understand the burden carried by patients. The current treatment landscape, while effective, is fraught with compromises. The first-generation standard, Xyrem, and the more recent once-nightly option, Lumryz, both contain a staggering amount of sodium—approximately 1,640 mg at the maximum dose. This single-handedly exceeds the American Heart Association’s ideal daily limit of 1,500 mg, a serious concern for a patient population already at a higher risk for hypertension and cardiovascular disease.

“Every night, it’s a calculation,” one patient shared on an online forum. “I know this medicine helps me function during the day, but I can’t stop thinking about what the salt is doing to my heart long-term.”

In response to this risk, another product, Xywav, was introduced with 92% less sodium. While a major step forward for cardiovascular health, it retained the other significant drawback of the original therapy: a twice-nightly dosing regimen. Patients must take one dose at bedtime and then wake themselves with an alarm 2.5 to 4 hours later to take a second. This forced interruption perpetuates the very sleep fragmentation the medication is supposed to treat.

“They call it ‘alarm anxiety’ for a reason,” explained a caregiver for a spouse with narcolepsy. “You go to bed dreading the alarm. Sometimes he can’t fall back asleep, and the next day is a write-off. It feels like you’re solving one problem by creating another.” This disruptive schedule impacts adherence, with studies and patient anecdotes revealing that many struggle with or skip the second dose, compromising the treatment's efficacy.

This is the paradox TRN-257 aims to solve. As Maurice M. Ohayon, MD, DSc, PhD, of the Stanford Sleep Epidemiology Research Center noted, “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.”

Engineering a Better Patient Experience

The innovation behind TRN-257 is not a new chemical entity but a feat of pharmaceutical engineering. Tris Pharma has leveraged two of its proprietary drug delivery platforms, LiquiXR® and RaftWorks™, to create a sophisticated release profile that was previously out of reach.

LiquiXR® is a particle-based technology that has been the backbone of several previously approved drugs. It works by binding the active drug to tiny, ion-exchange resin particles. These particles are then coated with a polymer film. Once ingested, ions in the gastrointestinal (GI) tract swap places with the drug, allowing it to be released and absorbed steadily over time. By varying the thickness of the coating, the technology can program a sustained release that lasts for hours, all from a single dose.

The RaftWorks™ platform adds another layer of control. It creates an “in-situ floating raft” in the stomach from an inter-penetrating polymer network. This raft slowly and continuously releases the drug in the upper GI tract, an area of the body with a narrow window for absorption. The combination of these technologies allows TRN-257 to deliver its therapeutic payload throughout the night from a single administration, mimicking the effect of a second dose without requiring the patient to wake up.

This focus on the delivery mechanism underscores a critical aspect of modern medicine: the patient experience is an integral part of therapeutic efficacy. To that end, the company’s NDA submission included a comprehensive Human Factors Engineering and Usability study, which validated that patients could easily prepare and use the product as intended, a crucial step in building trust with a community accustomed to complex and burdensome regimens.

Reshaping a Multi-Billion-Dollar Market

The FDA’s acceptance of the NDA sets a Prescription Drug User Fee Act (PDUFA) goal date of June 20, 2026, marking the start of a new chapter in a highly competitive and lucrative market. The global narcolepsy therapeutics market is estimated to be worth over $3.5 billion and is projected to grow to more than $6 billion by 2030.

Currently, the market is a battleground of trade-offs. Jazz Pharmaceuticals' Xyrem and Xywav have long dominated, with Avadel Pharmaceuticals' Lumryz recently entering the fray as the first once-nightly option. TRN-257 is poised to challenge this dynamic by offering a “best of both worlds” solution: the convenience of Lumryz and the low-sodium profile of Xywav. If approved, it could significantly disrupt the market by capturing patients and physicians seeking a simpler, safer long-term treatment.

As a privately held company, Tris Pharma has a history of leveraging strategic partnerships to commercialize its innovations, particularly outside the United States. The press release confirms it is actively exploring US and global partners for TRN-257. This strategy allows the company to focus on its core strength—solving complex formulation challenges—while relying on partners with established commercial infrastructure to bring the product to a global patient population. Finding the right partner will be critical to navigating the entrenched competition and realizing the drug’s full market potential.

The road ahead involves a thorough FDA review of the submitted data, which relies on pharmacokinetic studies and modeling rather than large-scale efficacy trials, a common approach for 505(b)(2) applications that bridge to existing approved drugs. For the thousands of patients with narcolepsy and IH, the next two years will be a period of watchful waiting, hoping that this innovative approach to drug delivery will finally grant them the restorative, uninterrupted night of sleep they have been seeking for so long.