The study will be presented today during the 2021 American Academy of Neurology Annual Meeting.
Jazz Pharmaceuticals today announced favorable results from its phase 3 clinical trial of a mixed-salts oral solution for the treatment of adults with idiopathic hypersomnia (IH).1
The study data will be presented during the Clinical Trials Plenary Session of the 2021 American Academy of Neurology (AAN) Annual Meeting today.
Patients with IH experience chronic excessive daytime sleepiness, which is characterized by the inability to stay awake and alert during the day; consequently, patients suffer an irrepressible need to sleep or unplanned lapses into sleep or drowsiness that is unrelated to other medical, behavioral, or psychiatric conditions. Additionally, IH can manifest through prolonged main sleep episodes of more than 9 hours, sleep durations of 11 hours or more over a 24-hour period, prolonged and non-restorative nighttime sleep, long and unrefreshing naps, and severe sleep inertia.
The calcium, magnesium, potassium, and sodium oxybates oral solution (Xywav, also called JZP-258) is a lower-sodium oxybate that has been approved by the FDA for the treatment of cataplexy or excessive daytime sleepiness in individuals 7 years of age and older with narcolepsy and is currently being investigated for the treatment of IH in adults. Though investigators have not pinned down the treatment’s precise method of action, it is hypothesized that JZP-258 employs γ-aminobutyric acid metabotropic receptors (GABAB) during sleep at noradrenergic and dopaminergic neurons, as well as thalamocortical neurons.
The phase 3, multi-national, double-blind, multicenter, placebo-controlled randomized withdrawal study included 154 patients between the ages of 18 and 75 years diagnosed with IH according to the International Classification of Sleep Disorders ICSD-2 or ICSD-3 criteria.2 Investigators evaluated change in Epworth Sleepiness Scale (ESS) score within a 2-week time frame, with lower scores indicating less daytime sleepiness. The study design also included a titration and optimization period of up to 14 weeks, a JZP-258 stable-dose period (SDP) of 2 weeks, followed by 1:1 randomization to either the treatment group or placebo.1
Researchers from the study reported that at the end of the double-blind randomized withdrawal period, patients in the placebo group (n=59) experienced significant worsening in ESS scores compared with those continuing JZP-258 treatment (n=56). At the beginning of the study, participants displayed a mean Idiopathic Hypersomnia Severity Scale (IHSS) score of 31.6; by the end of SDP, the mean was 15.3.
The most comment adverse events (AEs) for JZP-258 were nausea (21.4%), headache (16.2%), dizziness (11.7%), anxiety (10.4%), and vomiting (10.4%).
"The dramatic improvements Xywav provided for participants within this study give hope to not only those living with idiopathic hypersomnia, but also to their families, friends and care teams," said Yves Dauvilliers, MD, director of the Sleep Disorders Centre at the Gui de Chauliac Hospital in Montpellier, France, and lead investigator of the phase 3 study.
"People with idiopathic hypersomnia sleep a normal, or longer than normal, amount of sleep each night, but still experience excessive sleepiness during the day.6,7 If the new indication is approved by the FDA, I believe Xywav will make an immediate impact on patients living with idiopathic hypersomnia."