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DUBLIN, Jan. 5, 2022 /PRNewswire/ -- Jazz Pharmaceuticals plc (Nasdaq: JAZZ) today announced positive data from the Phase 3 multicenter, placebo-controlled, double-blind, randomized withdrawal study of Xywav® (calcium, magnesium, potassium, and sodium oxybates) oral solution for the treatment of adults with idiopathic hypersomnia were published online in The Lancet Neurology.
The results of the Phase 3 clinical trial showed clinically meaningful and statistically significant differences with Xywav compared to placebo in the primary endpoint of change in the Epworth Sleepiness Scale (ESS) score and key secondary endpoints, which included measures that assessed patients' perceptions of the changes in their idiopathic hypersomnia overall (PGIc), symptom severity, including excessive daytime sleepiness (EDS), sleep inertia and prolonged sleep duration (Idiopathic Hypersomnia Severity Scale), and improved daytime performance.1 In August 2021, Xywav became the first and only drug approved for patients with idiopathic hypersomnia by the U.S. Food and Drug Administration (FDA).2 Xywav for idiopathic hypersomnia was made commercially available in November 2021.
"The full data set from the largest global Phase 3 trial in adults with idiopathic hypersomnia represents a major advance in this condition and will enable physicians to make more informed, evidence-driven treatment decisions," said Yves Dauvilliers, M.D., Ph.D., lead investigator of the study and director of the Sleep and Wake Disorders Centre in the Department of Neurology at the Gui de Chauliac Hospital in Montpellier, France. "The trial results demonstrate that Xywav offers significant and clinically meaningful improvements to multiple aspects of this debilitating condition that can benefit the sleep and daily lives of adults diagnosed with this unique sleep disorder."
Additionally, the FDA has recognized seven years of Orphan Drug Exclusivity for Xywav for the treatment of idiopathic hypersomnia in adults. The FDA's Orphan Drug Designation program is designed to advance the development of drugs that treat a condition affecting 200,000 or fewer U.S. patients annually. The seven-year market exclusivity for Xywav for idiopathic hypersomnia began on August 12, 2021, the date of FDA approval for this indication. In June 2021, the FDA recognized seven years of Orphan Drug Exclusivity for Xywav for the treatment of cataplexy or excessive daytime sleepiness in patients 7 years and older with narcolepsy.
Idiopathic hypersomnia is a debilitating neurologic sleep disorder characterized by chronic excessive daytime sleepiness, which is the inability to stay awake and alert during the day resulting in the irrepressible need to sleep or unplanned lapses into sleep or drowsiness. Core symptoms of idiopathic hypersomnia may include confusion, irritability and severe sleep inertia or sleep drunkenness (prolonged difficulty in waking up with frequent reentries into sleep). In addition, people with idiopathic hypersomnia may experience prolonged, non-restorative nighttime sleep, cognitive impairment in thinking, and long and unrefreshing naps.3,4,5,6
"Xywav is the only FDA-approved medicine available to treat idiopathic hypersomnia, providing clinicians with an effective and meaningful option for their patients to help relieve symptoms like sleep inertia and excessive daytime sleepiness," said Rob Iannone, M.D., M.S.C.E., executive vice president, research and development and chief medical officer of Jazz Pharmaceuticals. "We are committed to addressing the debilitating unmet needs of patients with neurological disorders through the development of novel medicines that can transform lives, and our launch of Xywav for use in idiopathic hypersomnia is one example of Jazz's evolved R&D capabilities."
Phase 3 Trial ResultsIn the trial (NCT03533114), investigators at 50 centers in seven countries enrolled a total of 154 adults aged 19 to 75 diagnosed with idiopathic hypersomnia. Following a screening period, the study had three dosing periods. First, participants received open-label Xywav for 10 to 14 weeks, until their individual doses were optimized. Optimized dose ranged from 2.5 to 9.0 grams per night. Patients then received stable, optimized doses for two weeks, with median doses of 4.5 ((interquartile range [IQR], (3.0 to 5.0) grams nightly (one dose regimen, 21 patients) and 7.5 (IQR 6.5 to 8.1) grams nightly (two-dose regimen, 93 patients), with 40 patients changing dosing regiments once or more times. During a double-blind randomized withdrawal period (DBRWP), patients received either the optimized stable dose of Xywav or a placebo for two weeks.1
Participants entered the study with a mean (SD) ESS score of 16.1 (3.6), indicating substantial excessive daytime sleepiness. During the Xywav open-label titration and optimization period, ESS scores decreased, indicating improvement, which was maintained during the stable dose period (SDP).
The study's primary endpoint was change in the ESS scores as measured from the end of the SDP to the end of the DBRWP. Participants randomized to continue Xywav had stable mean (SD) ESS scores [from 6.3 (4.3) to 7.0 (5.0)], in contrast to those randomized to placebo whose mean (SD) ESS scores increased from 5.8 (3.7) to 13.3 (4.1) points, indicating worsening. The differences between the two group's mean ESS scores, [5.8 (3.7) to 13.3 (4.1)] were statistically significant, [95% Cl: -6.5 points (-8.0, -5.0), P
