Zevra Therapeutics, Inc. announced that final positive results from its placebo-controlled, double-blind Phase 2 clinical trial (NCT05668754) evaluating the safety and tolerability of KP1077 (serdexmethylphenidate or SDX) in patients with idiopathic hypersomnia (IH) were presented in a poster at SLEEP 2024, the 38th annual joint meeting of the American Academy of Sleep Medicine and the Sleep Research Society, held in Houston, TX, June 1-5, 2024. In addition, a second poster describing the pharmacokinetics of SDX when administered in the morning and at night was also presented. This proof-of-concept study was designed to demonstrate safety and tolerability and was not powered to demonstrate statistical significance.

However, the trial included several important secondary and exploratory endpoints, such as 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 the symptoms and severity of brain fog. These data gathered from the secondary endpoints will help inform the study design for a potential Phase 3 clinical trial of KP1077. Key Takeaways from Phase 2 Clinical Trial of KP1077 for Idiopathic Hypersomnia: KP1077 was well tolerated at all dose levels evaluated in the trial, including the highest dose of 320 mg daily, regardless of the dosing regimen: once daily (QD) or twice daily (BID).

Adverse events (AEs) were similar to other methylphenidate products,Most common AEs included insomnia, headache, anxiety, decreased appetite, and nausea, Most AEs occurred during the titration period, were mild, and did not lead to early discontinuation. KP1077 produced clinically meaningful improvements in EDS as assessed by change from baseline in the ESS during both the 5-week open-label (OL) titration period which was maintained during the 2-week double-blind withdrawal period for both dosing regimens.,Mean total ESS scores decreased by approximately 9 points after 5 weeks of OL treatment. At the end of 7 weeks of treatment, patients administered KP1077 showed clinically meaningful benefits in change from baseline for the ESS, IHSS, SIVAS, and Brain Fog Scale (BFS): Mean total ESS score decreased by 9.4 (QD) and 8.8 (BID), Mean total IHSS score decreased by 16.1 (QD) and 12.3 (BID), Mean SIVAS score decreased by 25.9 (QD) and 17.2 (BID),Mean total BFS symptom score decreased by 23.8 (QD) and 22.3 (BID).

The study successfully fulfilled the objectives of providing key information for the design of a pivotal efficacy trial, and the results of the secondary efficacy endpoints were supportive of initiating a Phase 3 trial of KP1077. Separately, the pharmacokinetics of morning and nighttime dose of KP1077 was studied. These data are also being presented in a poster at SLEEP 2024.

Key Takeaways from Pharmacokinetics of Morning and Nighttime Doses of KP1077 Based on the Phase 2 trial results, the Company believes that: Peak exposure of SDX-derived d-MPH after a nighttime dose of SDX occurs during the next morning leading to higher exposure at awakening compared to a morning dose. The delay in exposure is likely due to a longer intestinal transit time and lower intestinal activity during the nighttime sleeping hours.,The delay in exposure supports nighttime dosing of SDX in patients with IH who suffer from EDS and sleep inertia (difficulty waking up in the morning). Idiopathic hypersomnia (IH) is a rare sleep disorder characterized by excessive daytime sleepiness (EDS).

Patients with IH experience daytime lapses into sleep, or an irrepressible need to sleep that persists even with adequate or prolonged nighttime sleep. Additionally, those with IH have extreme difficulty waking, otherwise known as sleep inertia, severe brain fog, and often fall asleep unintentionally or at inappropriate times. These symptoms of IH often lead to further, even more debilitating problems such as memory lapses, difficulty maintaining focus, and depression.

It is estimated, based on claims data, that approximately 37,000 patients in the United States are currently diagnosed with IH, although the total patient population may be much larger due to some patients who have not yet been diagnosed, have been misdiagnosed, or are not currently seeking treatment. About KP1077: KP1077 (serdexmethylphenidate or SDX) is Zevra?s proprietary prodrug of d-methylphenidate (d-MPH) and its sole active pharmaceutical ingredient (API). KP1077 has been granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA), and by the European Commission, for the treatment of IH.

The U.S. Drug Enforcement Agency (DEA) has classified SDX, the sole API in KP1077, as a Schedule IV controlled substance based on evidence suggesting SDX has a lower potential for abuse when compared to d-MPH, a Schedule II controlled substance. In addition, KP1077 has intellectual property protection through 2037 and potentially beyond.