FDA Accepts sNDA for Oxybate Solution JZP-258 in Idiopathic Hypersomnia Treatment


The calcium, magnesium, potassium, and sodium oxybates solution, marketed as Xywav, was approved for cataplexy and daytime sleepiness in narcolepsy in July 2020.

Robert Iannone, MD, MSCE, executive vice president, research and development, and chief medical officer, Jazz Pharmaceuticals

Robert Iannone, MD, MSCE

Jazz Pharmaceuticals has announced that its supplemental new drug application (sNDA) for its calcium, magnesium, potassium, and sodium oxybates combination agent known as JZP-258 (marketed as Xywav) in the treatment of idiopathic hypersomnia was accepted by the FDA for review.1

The therapy won a fast track designation from the FDA in September 2020 for this indication, and in December was granted a rolling submission, allowing for the submission of portions of the application as completed. Jazz stated that it plans to bring JZP-258 to patients in the fourth quarter of 2021, pending its potential approval.

Currently, there are no approved agents for the treatment of idiopathic hypersomnia, with the majority of physicians turning to off-label use of wake-promoting therapies with effectiveness in those with narcolepsy to help address the sleepiness issues.2 Jazz noted in its release that data from insurance claims suggest that the prevalence of idiopathic hypersomnia includes more than 37,000 adults, but it is likely that many more remain undiagnosed.1

Diane Powell, Board Chair and CEO, Hypersomnia Foundation, echoed this sentiment in a statement, explaining that those with idiopathic hypersomnia often face delays to diagnosis, and many go their entire lives without identifying the condition. “Meanwhile, they struggle to keep up with school, work and relationships. We are encouraged by Jazz's progress and the possibilities for people living with idiopathic hypersomnia," she said.

Robert Iannone, MD, MSCE, executive vice president, research and development, and chief medical officer, Jazz Pharmaceuticals, told NeurologyLive that those living with idiopathic hypersomnia experience a number of issues from their disease—the absence of FDA-approved treatments specifically for their condition perched near the top of the list.

"Additionally, people with idiopathic hypersomnia often struggle to receive an accurate diagnosis as the diagnostic process is challenging, and the range of conditions leading to excessive sleepiness can be broad. As a leader in sleep medicine, we are committed to finding solutions for this community and helping sleep physicians to treat their patients living with this debilitating sleep disorder," he said.

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Positive topline data from a phase 3 study (NCT03533114) of the investigational use of the calcium, magnesium, potassium, and sodium oxybates oral solution were announced in October 2020, suggesting the agent is effective and safe for adult patients with idiopathic hypersomnia.3 The double-blind, multicenter, randomized clinical trial featured patients who had excessive daytime sleepiness associated with their idiopathic hypersomnia, and all of those treated with the agent experienced clinically meaningful improvements in Epworth Sleepiness Scale (ESS) scores—the primary end point—during the open-label titration period.

Both the primary and the key secondary end points (Patient Global Impression of Change [PGIC] and Idiopathic Hypersomnia Severity Scale [IHSS]) were measured during the randomized withdrawal portion of the study. That section included 115 patients, and those given the oxybates combination reported clinically meaningful maintenance of efficacy as measured by all 3 evaluations. As well, highly statistically significant worsening was observed for those administered placebo in comparison with the agent for ESS (P <.0001), PGIC (<.0001), and IHSS (P <.0001).

"This sNDA submission brings us one step closer to making this important treatment option available to patients living with idiopathic hypersomnia. [...] Jazz continues to invest in developing innovative treatments for patients with significant unmet needs. Jazz has spent over a decade researching the lower-sodium oxybate product, Xywav, in both narcolepsy and idiopathic hypersomnia," said Iannone in a statement.

"Our purpose is to innovate to transform the lives of patients and we are committed to collaborating with regulators, sleep experts, and patients to deepen our understanding of sleep disorders, and the science around sleep medicine," he added.

The oxybates combination was originally approved for the treatment of cataplexy or excessive daytime sleepiness (EDS) in patients 7 years of age or older with narcolepsy in July 2020. The basis of that approval was built on data suggesting that the drug demonstrated statistically significant differences (P <.0001) in the weekly number of cataplexy attacks and Epworth Sleepiness Scale scores compared to placebo in a phase 3 double-blind, placebo-controlled, randomized-withdrawal, multicenter study.4

Gamma hydroxybutyrate (GHB) is the active ingredient of the product, and abuse of illegal GHB alone or with other drugs can cause serious adverse effects. Among them include seizures, trouble breathing, changes in alertness, coma, and death.

1. 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 February 16, 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
2. About Treatment. Hypersomnia Foundation website. hypersomniafoundation.org/treatment. Revised February 2021. Accessed February 16, 2021.
3. Jazz Pharmaceuticals Announces Positive Top-line Results from Phase 3 Study of Xywav™ (calcium, magnesium, potassium, and sodium oxybates) Oral Solution in Adult Patients with Idiopathic Hypersomnia. News release. October 8, 2020. Accessed February 16, 2021. prnewswire.com/news-releases/jazz-pharmaceuticals-announces-positive-top-line-results-from-phase-3-study-of-xywav-calcium-magnesium-potassium-and-sodium-oxybates-oral-solution-in-adult-patients-with-idiopathic-hypersomnia-301148512.html
4. Jazz Pharmaceuticals announces US FDA approval of Xywav (calcium, magnesium, potassium, and sodium oxybates) oral solution for cataplexy or excessive daytime sleepiness associated with narcolepsy. News release. July 22, 2020. Accessed February 16, 2021. jazzpharma.com/news-releases/news-release-details/jazz-pharmaceuticals-announces-us-fda-approval-xywavtm-calcium
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