Zevra Therapeutics to Present Phase 2 Data on KP1077 for Idiopathic Hypersomnia at Sleep Europe 2024

Zevra Therapeutics, Inc., a company specializing in treatments for rare diseases, has unveiled significant top-line data from its Phase 2 clinical trial of KP1077 (serdexmethylphenidate, or SDX) for idiopathic hypersomnia (IH). The data were presented by Rene Braeckman, Ph.D., the Senior Vice President of Clinical Development at Zevra, during the 27th Congress of the European Sleep Research Society (ESRS) in Seville, Spain, from September 24-27, 2024.

The Phase 2 study, identified as NCT05668754, was a double-blind, placebo-controlled, randomized-withdrawal trial aimed at evaluating both the safety and efficacy of KP1077 in treating IH. Conducted across multiple centers, the study included a dose-optimizing procedure. In the first part of the trial, patients underwent a 5-week open-label dose titration phase to determine the optimal dose from among four possible dosages: 80, 160, 240, or 320 mg/day. Following this, the second part involved a two-week randomized withdrawal phase where two-thirds of the participants continued with their optimized dose while the remaining one-third received a placebo.

Participants were separated into two cohorts: one cohort took a single daily dose before bedtime, and the other split the dose between morning and bedtime. A total of 66 adult patients with IH were recruited from 24 centers in the U.S., out of which 50 continued into the double-blind phase of the study.

The primary endpoint of the study focused on the safety and tolerability of KP1077. Secondary efficacy endpoints included changes in the Epworth Sleepiness Scale (ESS) total score, the Idiopathic Hypersomnia Severity Scale (IHSS), and the Sleep Inertia Visual Analog Scale (SIVAS), along with a new scale to assess brain fog symptoms and severity.

Idiopathic hypersomnia is a rare condition marked by excessive daytime sleepiness (EDS) despite adequate or prolonged nighttime sleep. Patients often experience sleep inertia (difficulty waking), severe brain fog, and may unintentionally fall asleep during the day. These symptoms can lead to additional issues such as memory lapses, difficulty concentrating, and depression. Current data estimates that about 37,000 individuals in the United States are diagnosed with IH, though the actual number could be higher due to undiagnosed or misdiagnosed cases.

KP1077, the investigational treatment evaluated in this trial, is Zevra’s unique prodrug of d-methylphenidate (d-MPH). It has received Orphan Drug Designation from both the U.S. Food and Drug Administration (FDA) and the European Commission for the treatment of IH. The U.S. Drug Enforcement Agency (DEA) has classified serdexmethylphenidate (SDX), the sole active ingredient in KP1077, as a Schedule IV controlled substance, indicating a lower potential for abuse compared to d-MPH, which is classified as Schedule II. KP1077 benefits from intellectual property protection extending through 2037 and potentially beyond.

Zevra Therapeutics, Inc. is a commercial-stage company dedicated to developing and commercializing therapies for rare diseases, addressing unmet medical needs through innovative, data-driven strategies. The company aims to make transformative treatments accessible to the rare disease community, overcoming complex drug development challenges.

The data from the Phase 2 trial of KP1077 provide critical insights for the planning of a subsequent Phase 3 study, positioning Zevra to advance its mission of delivering life-changing treatments for individuals with rare diseases.