Filling a Critical Need for Idiopathic Hypersomnia With JZP-258 (Xywav)

Robert Iannone, MD, MSCE

Earlier this month, the FDA granted approval to JZP-258 (Xywav; Jazz Pharmaceuticals) for the treatment of idiopathic hypersomnia, making it the first treatment approved for the indication. The agent is a combination therapy consisting of calcium, magnesium, potassium, and sodium oxybates.¹

Jazz originally announced the acceptance of its supplemental new drug application (sNDA) for JZP-258 in April 2021 after completing the submission in February, which included data from a positive phase 3 study (NCT03533114) that showed the investigational agent was effective and safe for adults with idiopathic hypersomnia.² Previously, the oral solution received fast track designation from the FDA, and in December 2020 it was granted a rolling submission, allowing for the submission of portions of the application as it was completed.

Idiopathic hypersomnia is a debilitating neurologic sleep disorder characterized by chronic excessive daytime sleepiness (EDS), and with no therapies available prior to this decision, many physicians had turned to off-label use of wake-promoting therapies typically used in patients with narcolepsy to help address the sleepiness issues. To find out what the impact of this approval might be for those clinicians, NeurologyLive inquired with Robert Iannone, MD, MSCE, executive vice president, Research and Development, and chief medical officer, Jazz Pharmaceuticals, for more information.

NeurologyLive: What does this approval mean for sleep disorder physicians, who have only had off-label options to this point?

Robert Iannone, MD, MSCE: The recent approval of Xywav as the first and only treatment indicated for idiopathic hypersomnia provides healthcare providers with a FDA-approved therapy that may help manage their patients' symptoms, including excessive daytime sleepiness and severe sleep inertia.

Xywav [and Xyrem] is available only through the Xywav and Xyrem Risk Evaluation and Mitigation Strategies (REMS) Program using the Certified Pharmacy, which is very different from how other prescriptions are prescribed. Through REMS, prescribers and patients are educated on and understand the risks and safe use conditions of these medicines and agree to follow the requirements of the Xywav and Xyrem REMS.

Patient safety is extremely important to Jazz. We have worked with leading clinical experts, scientists, patient advocates and, most importantly, the FDA and the DEA, to ensure we are able to bring first of their kind treatments safely to patients.

What should the clinical community know about Xywav’s potential in idiopathic hypersomnia, specifically?

Prior to the recent approval of Xywav, there were no treatments approved by the FDA for the treatment of this sleep disorder. Idiopathic hypersomnia is a unique medical condition that warrants its own treatment option, and Jazz is proud to provide this first and only treatment option to patients. Xywav fulfills an unmet need for those diagnosed with this sleep disorder, offering them effective and safe management of their debilitating symptoms.

We are pleased with the outcome of the registrational phase 3 study, which showed statistically significant differences in the Epworth Sleepiness Scale score, Patient Global Impression of Change (P <.0001) and the Idiopathic Hypersomnia Severity Scale.

Additionally, Xywav can be administered as a twice- or once-nightly regimen for idiopathic hypersomnia. Results from the phase 3 trial of Xywav in idiopathic hypersomnia demonstrated efficacy of once-nightly dosing for those living with the disorder. Dosing flexibility, including once- or twice-nightly dosing or unequally divided doses, is clinically useful to tailor the dosing regimen based on what is right for the individual patient. To optimize the response, a patients' healthcare provider may suggest unequal doses at bedtime and/or gradually titrate Xywav so that a patient may receive an individualized dose based on efficacy and tolerability.

When will the agent be available for clinicians and patients to utilize?

Bringing this clinically meaningful improvement to patients is a priority for us, and we plan to launch Xywav in idiopathic hypersomnia later this year following REMS implementation. Xywav [and Xyrem] is available only through the Xywav and Xyrem REMS Program using the Certified Pharmacy, which is very different from how other prescriptions are prescribed.

Are there any plans to explore this agent in additional sleep disorders?

There are no other ongoing phase 3 studies of Xywav. While not necessarily focused on sleep, we also are working to expand our pipeline into other areas of neuroscience. A phase 2b clinical trial is currently being planned to assess the efficacy of JZP-385 [a highly selective modulator of T-type calcium channels] in the treatment of essential tremor.

Transcript edited for clarity.

REFERENCES
1. Jazz Pharmaceuticals Announces U.S. FDA Approval of Xywav® (calcium, magnesium, potassium, and sodium oxybates) Oral Solution for Idiopathic Hypersomnia in Adults. News release. Jazz Pharmaceuticals. August 12, 2021. Accessed August 17, 2021. https://www.prnewswire.com/news-releases/jazz-pharmaceuticals-announces-us-fda-approval-of-xywav-calcium-magnesium-potassium-and-sodium-oxybates-oral-solution-for-idiopathic-hypersomnia-in-adults-301354616.html
2. Jazz Pharmaceuticals Completes Submission of Supplemental New Drug Application for Xywav™ (calcium, magnesium, potassium, and sodium oxybates) Oral Solution for Idiopathic Hypersomnia. News release. February 16, 2021. Accessed August 17, 2021. prnewswire.com/news-releases/jazz-pharmaceuticals-completes-submission-of-supplemental-new-drug-application-for-xywav-calcium-magnesium-potassium-and-sodium-oxybates-oral-solution-for-idiopathic-hypersomnia-301228862.html