Solving Sleep Disorders
The US Food and Drug Administration (FDA) approved Dublin-based Jazz Pharmaceuticals’ Xywav (calcium, magnesium, potassium, and sodium oxybates) oral solution for the treatment of idiopathic hypersomnia in adults. Idiopathic hypersomnia is a debilitating neurological sleep disorder characterized by chronic excessive daytime sleepiness, explained Pharma Times.
According to Diane Powell, board chair and chief executive officer of the Hypersomnia Foundation, “Idiopathic hypersomnia can have a significant impact on the social, educational and occupational functioning of people living with the condition. Today’s FDA approval is a major milestone for the entire idiopathic hypersomnia community as Xywav becomes the first medicine approved to manage this chronic sleep disorder.”
“Idiopathic hypersomnia is a lifelong condition, and the approval of Xywav will be instrumental in providing treatment for symptoms such as excessive sleepiness and difficulty waking, and in effectively managing this debilitating disorder,” added Eric Bastings, M.D., deputy director of the Office of Neuroscience in the FDA Center for Drug Evaluation and Research.
This FDA approval is based on Jazz Pharmaceuticals’ Phase III study. Xywav demonstrated statistically significant and clinically meaningful differences in the primary endpoint of Epworth Sleepiness Scale and secondary endpoints of Patient Global Impression of Change and the Idiopathic Hypersomnia Severity Scale. FDA’s approval is for expanded use of Xywav in patients suffering from excessive daytime sleepiness despite a good night’s sleep.
The double-blind, placebo-controlled, randomized-withdrawal clinical trial included 154 adult patients aged 19 to 75 years. Patients who were switched from Xywav to a placebo experienced worsening sleepiness and symptoms of idiopathic hypersomnia compared with those who continued taking the drug, according to the FDA. The most common side effects of the drug were nausea (21.4 percent), headache (16.2 percent), dizziness (11.7 percent), anxiety (10.4 percent), and vomiting (10.4 percent). Xywav has developed a boxed warning for central nervous system depression and abuse and misuse, which can cause serious side effects such as seizures, trouble breathing, changes in alertness, coma, and death, the FDA said.
Because of the potential risks associated with Xywav, it is subject to strict safety controls on prescribing and dispensing under a program called a Risk Evaluation and Mitigation Strategy (REMS). Specifically, under the Xywav REMS, it can be prescribed only by a certified prescriber, and dispensed only to an enrolled patient by a certified pharmacy. Only a certified pharmacy that ships directly to patients can dispense Xywav. Xywav will not be available in retail pharmacies.
Xywav is the first drug to be approved by the FDA for idiopathic hypersomnia. The oral drug was already approved in the US for the treatment of excessive daytime sleepiness and sudden loss of muscle tone in patients aged 7 years and older with narcolepsy.
“The clinical program for Xywav has demonstrated that this lower-sodium oxybate is an effective therapy for the treatment of idiopathic hypersomnia,” explained Yves Dauvilliers, M.D., director of the Sleep Disorders Centre at the Gui de Chauliac Hospital in Montpellier, France, and lead investigator of the Phase III study.
FDA gave Xywav Fast Track designation in September 2020 for the treatment of idiopathic hypersomnia and Priority Review designation as part of the supplemental New Drug Application (sNDA) acceptance in April 2021. Xywav received approval in July 2020 for the treatment of cataplexy or excessive daytime sleepiness in patients seven years of age and older with narcolepsy.
Jazz Pharmaceuticals is planning to make Xywav available to patients with idiopathic hypersomnia later this year following Risk Evaluation and Mitigation Strategies (REMS) implementation.