Treatment of narcolepsy: A rare disease of unknown etiology

Background: Narcolepsy, also known as Gélineau syndrome, is a chronic and neurological disease that affects 0.05% of the European population, though that percentage could be higher due to the diagnostic difficulties. The main symptom is excessive daytime sleepiness, although it may be accompanied by cataplexy, sleep paralysis and hypnagogic hallucinations. Objective: Nowadays, there is no cure for narcolepsy and the treatment is symptomatic: psychostimulants for the sleepiness by means of amphetamines, methylphenidate or modafinil, and antidepressants and sodium oxybate for treating cataplexy. Method: This is a short review regarding pharmacotherapy for narcolepsy. Result: Hypocretins were discovered in 1998. They are neuropeptides whose deficit is responsible for this symptomatology, has opened up a new field of investigation. Conclusion: Agonists of hypocretins could be a promising therapy against this disease.

Once-Nightly Sodium Oxybate (FT218) Demonstrated Improvement of Symptoms in a Phase 3 Randomized Clinical Trial in Patients With Narcolepsy

Study Objectives To assess the efficacy and safety of FT218, a novel once-nightly formulation of sodium oxybate (ON-SXB), in patients with narcolepsy in the phase 3 REST-ON trial. Methods Narcolepsy patients aged ≥16 years were randomized 1:1 to uptitration of ON-SXB (4.5, 6, 7.5, and 9 g) or placebo. Three coprimary endpoints were change from baseline in mean sleep latency on the Maintenance of Wakefulness test, Clinical Global Impression-Improvement rating, and weekly cataplexy attacks at 9, 7.5, and 6 g. Secondary endpoints included change from baseline on the Epworth Sleepiness Scale. Safety included adverse drug reactions and clinical laboratory assessments. Results In total, 222 patients were randomized; 212 received ≥1 dose of ON-SXB (n=107) or placebo (n=105). For the 3 coprimary endpoints and Epworth Sleepiness Scale, all 3 doses of ON-SXB demonstrated clinically meaningful, statistically significant improvement vs placebo (all P<0.001). For ON-SXB 9 g vs placebo, increase in mean sleep latency was 10.8 vs 4.7 min (LSMD [95% CI], 6.13 [3.52–8.75]), 72.0% vs 31.6% were rated much/very much improved on Clinical Global Impression-Improvement (OR [95% CI], 5.56 [2.76–11.23]), change in mean weekly number of cataplexy attacks was –11.5 vs –4.9 (LSMD [95% CI], –6.65 [–9.32 to –3.98]), and change in Epworth Sleepiness Scale was –6.5 and –2.7 (LSMD [95% CI], –6.52 [–5.47 to –2.26]). Common adverse reactions included nausea, vomiting, headache, dizziness, and enuresis. Conclusions ON-SXB significantly improved narcolepsy symptoms; its safety profile was consistent with SXB. ON-SXB conferred efficacy with a clearly beneficial single nighttime dose.