KP1077 Is Safe, Tolerable for Improving Idiopathic Hypersomnia Symptoms

Christopher Drake, PhD, FAASM, DBSM

Credit: Henry Ford Health

Topline results from a phase 2 trial supported the safety and tolerability of KP1077 for idiopathic hypersomnia, announced by Zevra Therapeutics on March 26, 2024. The data suggests KP1077 provides clinically meaningful improvements for idiopathic hypersomnia symptoms.¹

“During the open-label dose titration period, patients showed robust improvements in [idiopathic hypersomnia] symptom severity, including excessive daytime sleepiness that were maintained during the double-blind withdrawal period,” said lead investigator Christopher Drake, PhD, FAASM, DBSM, in a press release. “At the end of the study, patients randomized into the KP1077 treatment group also demonstrated improvements in patient reported [idiopathic hypersomnia] specific outcomes.”

Idiopathic hypersomnia is a rare sleep disorder associated with excessive daytime sleepiness. It is estimated approximately 37,000 patients in the US are currently diagnosed with hypersomnia, are there might be many more who are not yet diagnosed, misdiagnosed, or not seeking treatment. Other than experiencing daytime lapses into sleep, sleep inertia, and brain fog, idiopathic hypersomnia can lead to more debilitating problems including memory issues, difficulty staying focused, and depression.

Back in 2021, the US Food and Drug Administration (FDA) approved Xywav for the treatment of idiopathic hypersomnia in adults.² Clinicians might prescribe stimulants to ease symptoms or other medications suggested by the American Academy of Sleep Medicine.³

Luckily for those with idiopathic hypersomnia, KP1077 (serdexmethylphenidate) shows promise in terms of alleviating these life-impacting symptoms.1 The FDA granted KP1077 the Orphan Drug Designation for the treatment of idiopathic hypersomnia, and the US Drug Enforcement Agency has classified serdexmethylphenidate—the sole active pharmaceutical ingredient in KP1077—as a Schedule IV controlled substance due to evidence showing it has a lower potential for abuse when compared to d-MPH, a Schedule II controlled substance. Due to the positive data, Zevra Therapeutics plans on requesting an end-of-phase 2 meeting with the FDA to hear input on the phase 3 clinical trial design.

Investigators conducted a placebo-controlled, double-blind, multicenter phase 2 trial to evaluate the safety and tolerability of KP1077 in patients with idiopathic hypersomnia. The study included two parts.

The first part of the trial included a 5-week open-label dose titration phase where 66 patients from 24 centers in the US were optimized to 1 of the following doses of KP1077: 80, 160, 240, 320 mg/day. The second part of the trial included a 2-week, randomized, double-blind, withdrawal phase, where two-thirds of participants continued receiving their optimized dose and the rest received a placebo. Only 50 participants continued into the second part of the trial. Participants were randomized into 2 even cohorts: one who received a single daily dose before bedtime, and the other who received half the daily dose soon after waking up and the second half before bedtime.

The study was not designed to demonstrate statistical significance but gathered data to inform the phase 3 study design. The primary endpoint was the safety and tolerability of KP1077, and the secondary endpoints included the change from baseline in the Epworth Sleepiness Scale, Idiopathic Hypersomnia Severity Scale, and Sleep Inertia Visual Analog Scale, and a scale to evaluate symptoms and severity of brain fog.

Investigators found clinically meaningful improvement in excessive daytime sleepiness, assessed by change from baseline in the Epworth Sleepiness Scale. Improvements were maintained during both the 5-week open-label titration period and through the 2-week double-blind withdrawal period.

Participants also had improvements from baseline in the Idiopathic Hypersomnia Severity Scale, Sleep Inertia Visual Analog Scale, and Brain Fog Severity Scale at the end of both the open-label dose titration and the withdrawal period.

Overall, investigators saw KP1077 was well-tolerated at various doses. The highest dose was 320 mg per day, and participants either had a dosing regimen of once or twice daily. Common adverse events were insomnia, headache, anxiety, nausea, and decreased appetite but they were mostly mild in severity.

The company said they believe KP1077 can have the potential to improve several key idiopathic hypersomnia symptoms, such as excessive daytime sleepiness, sleep inertia, and brain fog.

“We look forward to presenting the final results of the Phase 2 trial at the upcoming SLEEP 2024 annual meeting,” Drake said.

^References

1. ^{Zevra Therapeutics Announces Top-Line Data from the Phase 2 Clinical Trial of KP1077 for Idiopathic Hypersomnia. Global News Wire. March 26, 2024. https://www.globenewswire.com/news-release/2024/03/26/2852762/16626/en/Zevra-Therapeutics-Announces-Top-Line-Data-from-the-Phase-2-Clinical-Trial-of-KP1077-for-Idiopathic-Hypersomnia.html. Accessed March 28, 2024.}
2. ^{FDA Grants First of its Kind Indication for Chronic Sleep Disorder Treatment. FDA. August 12, 2021. https://www.fda.gov/news-events/press-announcements/fda-grants-first-its-kind-indication-chronic-sleep-disorder-treatment. Accessed March 28, 2024.}
3. ^{Idiopathic hypersomnia. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/hypersomnia/diagnosis-treatment/drc-20362338. Accessed March 28, 2024.}