Zevra Therapeutics announced top-line data from its Phase 2 clinical trial of KP1077 (serdexmethylphenidate, or SDX) for the treatment of idiopathic hypersomnia (IH). The data, presented at Sleep Europe 2024 in Seville, Spain, showed clinically meaningful benefits for key IH symptoms. The Phase 2 trial was a placebo-controlled, double-blind, randomized withdrawal study designed to evaluate the safety and tolerability of KP1077 in patients with IH.
Trial Design and Key Endpoints
The Phase 2 trial (NCT05668754) was a multi-center study that enrolled 66 adult patients with IH across 24 centers in the U.S. The trial consisted of two parts: a 5-week open-label dose titration phase, followed by a 2-week randomized, double-blind, withdrawal phase. During the open-label phase, patients were optimized to one of four doses of KP1077 (80, 160, 240, or 320 mg/day). In the double-blind phase, two-thirds of the participants continued on their optimized dose, while the remaining one-third received placebo.
The primary endpoint of the trial was the safety and tolerability of KP1077. Major secondary efficacy endpoints included the change in Epworth Sleepiness Scale (ESS) total score, the IH Severity Scale (IHSS), the Sleep Inertia Visual Analog Scale (SIVAS), and a new scale to assess brain fog.
Idiopathic Hypersomnia (IH) and Unmet Needs
Idiopathic hypersomnia is a rare sleep disorder characterized by excessive daytime sleepiness (EDS), affecting an estimated 37,000 diagnosed patients in the United States. Patients with IH experience daytime lapses into sleep, an irrepressible need to sleep despite adequate nighttime sleep, difficulty waking (sleep inertia), severe brain fog, and unintentional sleep at inappropriate times. These symptoms can lead to memory lapses, difficulty maintaining focus, and depression.
KP1077: A Potential New Treatment Option
KP1077 (serdexmethylphenidate or SDX) is Zevra’s proprietary prodrug of d-methylphenidate (d-MPH). It has been granted Orphan Drug Designation by the FDA and the European Commission for the treatment of IH. The U.S. Drug Enforcement Agency (DEA) has classified SDX as a Schedule IV controlled substance, suggesting a lower potential for abuse compared to d-MPH, which is a Schedule II controlled substance. Zevra Therapeutics anticipates that the top-line data from this Phase 2 trial will provide key information for the design of a Phase 3 study.
