The phase 2 trial explored the safety and efficacy of KP1077 in reducing daytime sleepiness and sleep inertia, with results presented at SLEEP 2024.


Summary: Zevra Therapeutics Inc. announced final positive results from its phase 2 clinical trial evaluating KP1077 (serdexmethylphenidate or SDX) for idiopathic hypersomnia (IH). The trial, which assessed the safety and tolerability of KP1077, also showed improvements in daytime sleepiness and other symptoms associated with IH. These results, presented at SLEEP 2024, support the potential of KP1077 as a treatment option for IH patients and pave the way for a phase 3 clinical trial. Additionally, a separate study on the pharmacokinetics of morning and nighttime doses of KP1077 was also presented.

Key Takeaways:

  • KP1077 was well tolerated across all doses, with most adverse events being mild and transient, similar to other methylphenidate products.
  • Patients showed reductions in daytime sleepiness, as measured by the Epworth Sleepiness Scale, with a mean decrease of 9 points after five weeks of treatment.
  • KP1077 demonstrated clinically meaningful improvements in IH symptom severity, including reductions in sleep inertia, excessive daytime sleepiness, and brain fog, as measured by various scales.
  • The pharmacokinetics study revealed that nighttime dosing of KP1077 leads to higher exposure at awakening, supporting its potential use for patients experiencing excessive daytime sleepiness and sleep inertia.

Zevra Therapeutics Inc announced that final positive results from its placebo-controlled, double-blind phase 2 clinical trial evaluating the safety and tolerability of KP1077 (serdexmethylphenidate or SDX) in patients with idiopathic hypersomnia (IH) were presented in a poster at SLEEP 2024. 

In addition, a second poster describing the pharmacokinetics of SDX when administered in the morning and at night was also presented.

“We are encouraged by the positive results of the phase 2 clinical trial, which serve as further support of KP1077 as a strong candidate to treat patients struggling with idiopathic hypersomnia,” says Adrian Quartel, MD, FFPM, chief medical officer of Zevra, in a release. “We believe that KP1077 has great potential to provide a differentiated treatment option for patients underserved by currently available therapies.”

Studying Safety and Tolerability of KP1077

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 secondary and exploratory endpoints, such as change in Epworth Sleepiness Scale total score, the IH Severity Scale, the Sleep Inertia Visual Analog Scale, 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.

“The results of the phase 2 clinical trial support the safety and tolerability of KP1077 as measured by the primary endpoint of the study,” says Christopher Drake, PhD, FAASM, DBSM, principal investigator of the study, in a release. “The clinically meaningful impact for both the safety and efficacy were well demonstrated by patients showing significant improvements in IH symptom severity such as sleep inertia, excessive daytime sleepiness, and patient-reported IH-specific outcomes.”

Clinical Trial Highlights of KP1077 for IH

Key Takeaways from the phase 2 clinical trial of KP1077 for IH include: 

  • 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 excessive daytime sleepiness as assessed by change from baseline in the Epworth Sleepiness Scale during both the five-week open-label titration period which was maintained during the two-week double-blind withdrawal period for both dosing regimens.
    • Mean total Epworth Sleepiness Scale scores decreased by approximately 9 points after five weeks of open-label treatment.
  • At the end of seven weeks of treatment, patients administered KP1077 showed clinically meaningful benefits in change from baseline for the Epworth Sleepiness Scale total score, the IH Severity Scale, the Sleep Inertia Visual Analog Scale, and Brain Fog Scale:
    • Mean total Epworth Sleepiness Scale score decreased by 9.4 (QD) and 8.8 (BID)
    • Mean total IH Severity Scale score decreased by 16.1 (QD) and 12.3 (BID)
    • Mean Sleep Inertia Visual Analog Scale score decreased by 25.9 (QD) and 17.2 (BID)
    • Mean total Brain Fog Scale 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.

Studying Pharmacokinetics of Dose Timing

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 experience from Excessive Daytime Sleepiness and sleep inertia (difficulty waking up in the morning).

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