Q1 Sleep Medicine Updates

In the first quarter of 2025, sleep medicine saw a mix of regulatory shifts and promising clinical data. Although the US Food and Drug Administration (FDA) rejected the New Drug Application (NDA) for pitolisant in idiopathic hypersomnia, plans for a new registrational trial are underway.

Emerging evidence also underscored the broader health impacts of poor sleep and highlighted therapeutic advances that may improve fatigue and sleep-related quality of life across diverse patient populations.

Q1 2025 Regulatory Updates in Sleep

FDA Rejects Pitolisant NDA for Idiopathic Hypersomnia

Harmony Biosciences received a Refusal to File (FTL) letter by the FDA for its supplemental NDA for pitolisant for the treatment of excessive daytime sleepiness in adult patients with idiopathic hypersomnia.

Despite this letter, it is not over for pitolisant. Harmony Biosciences plans to conduct a double-blind, randomized, parallel-group phase 3 registrational trial in patients with idiopathic hypersomnia. This study, with its design created with input from the FDA, will begin in Q4 2025.

Investigators assessed the efficacy of pitolisant in the phase 3 INTUNE study, which failed to meet the primary outcome for statistical significance in excessive daytime sleepiness between pitolisant and placebo in the randomized withdrawal phase. However, data from the open-label phase demonstrated improvements with pitolisant on the Epworth Sleepiness Scale that were 5 times greater than what is recognized as clinically meaningful. Most patients in the long-term extension study achieved normal levels of wakefulness sustained for > 1 year.

Clinical Trial Updates in Sleep

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

Phase 3 data from APPLY-PNH and APPOINT-PNH trials show that iptacopan, an oral complement factor B inhibitor, significantly improves fatigue and quality of life in patients with paroxysmal nocturnal hemoglobinuria (PNH), regardless of prior C5 inhibitor (C5i) treatment.

APPLY-PNH assessed C5i-experienced patients with persistent anemia, while APPOINT-PNH focused on C5i-naïve patients. In both trials, patients receiving iptacopan were more likely to achieve meaningful improvements in FACIT-Fatigue and EORTC QLQ-C30 scores compared with those on C5i therapy. Hemoglobin increases and lactate dehydrogenase reductions were strongly correlated with improved fatigue scores.

Notably, 51% of iptacopan-treated patients in APPLY-PNH reached the meaningful within-patient change threshold for FACIT-Fatigue versus 11% on C5i. In APPOINT-PNH, 56% reached this threshold. The results highlight iptacopan’s potential to deliver clinically meaningful disease control and alleviate the burden of fatigue in both C5i-naïve and -experienced PNH patients after 168 days of treatment.

Poor Sleep Quality Linked to Greater Blood Pressure in Adults with Optimal Sleep Duration

A recent study found that poor subjective sleep quality is associated with greater systolic blood pressure in adults aged ≤ 49 years, even when they get optimal sleep duration (6–7.9 hours). Among younger adults, those with poor sleep had a significantly greater average systolic blood pressure (127.8 mm Hg) than those with good sleep quality (121.0 mm Hg; P = .01). No such difference was found in participants aged ≥ 50 years.

Investigators suggested that the sympathetic nervous system's diminished responsiveness with age may explain the age-related differences. The study underscores that even among individuals with healthy sleep duration, subjective sleep quality may be an important marker for hypertension risk, particularly in younger adults.

Narrative Review Links Allergies and Impaired Sleep in Children

A recent narrative review highlights the strong association between childhood allergies and sleep disturbances, such as insomnia and obstructive sleep apnea (OSA). Allergic conditions, including allergic rhinitis, asthma, and atopic dermatitis can disrupt sleep through symptoms such as nasal congestion, itching, and wheezing. These disturbances may impair cognitive function, behavior, and overall well-being in children.

The review, which included research from Saudi Arabia—a region with high rates of pediatric allergies—emphasizes that poor sleep and allergy symptoms often exacerbate each other. Effective management involves addressing both conditions concurrently. Treatment options include pharmacological therapies (e.g., antihistamines, corticosteroids), lifestyle modifications, and behavioral therapies like cognitive-behavioral therapy for insomnia. More advanced interventions such as CPAP therapy, adenotonsillectomy, and various forms of immunotherapy—including emerging methods like epicutaneous and intralymphatic immunotherapy—may also be considered. The review underscores the importance of personalized, comprehensive care.