The past year brought several important updates in sleep medicine, including new US Food & Drug Administration (FDA) approvals, trial results, and guideline changes with direct implications for clinical practice. These updates affected the management of obstructive sleep apnea (OSA), narcolepsy, restless legs syndrome (RLS), and idiopathic hypersomnia (IH), giving clinicians additional evidence-based treatment options.

Clinical research highlighted alternative therapies, optimized treatment strategies, and novel mechanisms of action for sleep disorders. Check out the top 7 sleep health news stories from 2025.

FDA News

FDA Rejects Pitolisant NDA for Idiopathic Hypersomnia

Harmony Biosciences received a Refusal to File (RTF) from the FDA for its supplemental New Drug Application (NDA) seeking approval of pitolisant (WAKIX) to treat excessive daytime sleepiness in adults with IH. The Phase 3 INTUNE study did not meet its primary endpoint during the randomized withdrawal phase, though open-label data showed clinically meaningful improvements on the Epworth Sleepiness Scale, with most patients maintaining normal wakefulness for over a year.

Pitolisant, already approved for narcolepsy-related sleepiness and cataplexy, is a selective H₃ receptor antagonist. Harmony plans to conduct a pivotal phase 3 trial for an enhanced formulation, Pitolisant HD, targeting a 2028 PDUFA date.

Related: Pitolisant Shows Benefit for IH in Phase 3 Open-Label Trial, with Bruce Corser, MD

FDA Grants Approval of Hypoglossal Nerve Stimulation System for Obstructive Sleep Apnea Treatment

The FDA has approved Nyxoah’s Genio hypoglossal nerve stimulation system for adults with moderate to severe OSA and an apnea-hypopnea index (AHI) of 15–65. The leadless, bilateral stimulation system features a wearable, nonimplanted battery compatible with MRI.

DREAM trial data demonstrated significant reductions in AHI and Oxygen Desaturation Index (ODI), with 82% of participants achieving an AHI < 15. Efficacy was consistent across supine and nonsupine positions, addressing a key challenge in OSA treatment. Safety was favorable, with few device-related serious adverse events.

FDA Clears Kricket PAP Device for OSA

On December 17, 2025, SleepRes announced that the FDA had cleared its Kricket Positive Airway Pressure (PAP) device for obstructive sleep apnea in patients who weigh > 66 pounds. KPAP technology is designed to reduce CPAP-related discomfort by synchronizing therapy with a patient’s natural breathing and airway dynamics.

The device offers the KPAP algorithm alongside traditional CPAP and automatic PAP modes. SleepRes plans to launch Kricket for use at home, in hospitals, or other institutions in the first half of 2026.

Trial Updates and New Guidelines

RLS Guidelines Advise Against Dopamine Agonists, With John Winkelman, MD, PhD

At SLEEP 2025, John W. Winkelman, MD, PhD, highlighted the American Academy of Sleep Medicine’s updated guidelines advising against dopamine agonists for restless legs syndrome (RLS) due to augmentation risks.

The guidelines now favor iron therapies—oral or intravenous—and alpha-2-delta ligands such as gabapentin, gabapentin enacarbil, and pregabalin. Winkelman emphasized a gradual transition strategy, addressing aggravating factors like serotonergic antidepressants, sleep apnea, and alcohol, before slowly tapering dopamine agonists over 6–12 months, ensuring safer, more effective RLS management for long-term patient outcomes.

Axsome Presents Positive Phase 3 Data for AXS-12 in Narcolepsy at SLEEP 2025

Axsome Therapeutics presented positive phase 3 ENCORE and SYMPHONY data at SLEEP 2025, showing roboxetine (AXS-12) significantly reduced cataplexy attacks and improved daytime functioning in patients with narcolepsy.

Roboxetine, a selective norepinephrine reuptake inhibitor and cortical dopamine modulator with FDA Orphan Drug Designation, enhanced wakefulness, cognition, and overall patient function. ENCORE results showed a lower mean weekly cataplexy frequency versus placebo during a randomized-withdrawal period.

Aroxybutynin and Atomoxetine (AD109) Reduces Obstructive Sleep Apnea Burden in Phase 3 SynAIRgy

Phase 3 SynAIRgy data demonstrated that the combination therapy AD109—aroxybutynin plus atomoxetine—significantly reduced AHI scores and improved oxygen desaturation and hypoxic burden in adults with OSA. Conducted over 26 weeks in 639 participants intolerant of positive airway pressure therapy, AD109 improved AHI4 events by 55.6% versus placebo and enhanced fatigue and sleep impairment scores.

The oral regimen, combining an antimuscarinic and norepinephrine reuptake inhibitor, was well-tolerated, with manageable adverse events. These results support Apnimed’s plans to submit an FDA New Drug Application for AD109, offering a promising treatment for OSA.

Tirzepatide Shows Consistent Benefit for OSA Regardless of Baseline Severity

A post-hoc analysis of the Phase 3 SURMOUNT-OSA trials showed that tirzepatide provided consistent benefits in adults with moderate to severe OSA and obesity, regardless of baseline OSA severity or use of PAP therapy. The analysis revealed significant improvements compared to the placebo in AHI, sleep apnea–specific hypoxic burden, systolic blood pressure, C-reactive protein, and body weight across all severity subgroups. Tirzepatide increased the likelihood of achieving clinically meaningful AHI reductions in nearly all groups, with no consistent association between baseline severity and treatment response.

Phase 3 Data Shows Iptacopan Eases Fatigue in C5i-Experienced, -Naïve PNH Patients

Phase 3 trials APPLY-PNH and APPOINT-PNH demonstrate that iptacopan, a first-in-class oral selective complement factor B inhibitor, significantly improves fatigue, quality of life, and hematologic outcomes in patients with paroxysmal nocturnal hemoglobinuria (PNH). In C5 inhibitor-experienced and C5i-naïve patients, iptacopan monotherapy increased hemoglobin and reduced lactate dehydrogenase.

APPLY-PNH showed 51% of C5i-experienced patients achieved meaningful fatigue improvement versus 11% with prior therapy. APPOINT-PNH reported 56% of C5i-naïve patients reached fatigue improvement thresholds.