Adrian Quartel, MD: Next Steps for Evaluating KP1077 in Idiopathic Hypersomnia

Phase 2 data revealed KP1077 (serdexmethylphenidate or SDX) meaningfully improves excessive daytime sleepiness, sleep inertia, brain fog, and patient-reported outcomes in patients with idiopathic hypersomnia. Zevra Therapeutics announced the positive results on June 3, 2024, during SLEEP 2024, the 38th annual meeting of the Associated Professional Sleep Societies in Houston.

The phase 2 proof-of-concept, placebo-controlled, double-blind trial sought to evaluate the efficacy and safety of KP1077 in patients with idiopathic hypersomnia. Patients (n = 50) were split into groups of once-a-day-dosing and twice-a-day dosing), followed by being randomized 2:1 to either the study or placebo group. Each arm only had 25 participants.

Investigators saw KP1077 was well-tolerated at all doses, even at the highest dose (320 mg). Adverse events were comparable to other methylphenidate products, and the most common ones were insomnia, headache, anxiety, decreased appetite, and nausea. Most adverse events appeared during the titration period and were mild.

“We are very confident in regards to the safety profile, both cardiovascular as well as neurological,” Adrian Quartel, MD, the Chief Medical Officer of Zevra Therapeutics, told HCPLive. “This is a very clean drug. We know that it's the methylphenidate itself has been on the market for 20 plus years, serdexmethylphenidate has been used in thousands of patients, so we are confident that KP1077 is an appropriate and safe drug for patients.”

KP1077 provided clinically meaningful improvements in excessive daytime sleepiness from baseline, based on the Epworth Sleepiness Scale. The mean total Epworth Sleepiness Scales scores reduced by approximately 9 points after 5 weeks of treatment. The improvement was maintained during the 2-week double-blind withdrawal period for both dosing regimens.

The once-a-day-dosing group had greater reduced scores in the mean total Epworth Sleepiness Scales (reduction: 9.4 vs 8.8), mean total IH Severity Score (16.1 vs 12.3) Sleep Inertia Visual Analog Scale (25.9 vs 17.2), and Brain Fog Score (23.8 vs 22.3) than the twice-a-day dosing group.

As for morning and night doses, patients had a peak exposure of SDX-derived d-MPH after a nighttime dose of KP1077 during the next morning rather than the morning dose.

Zevra Therapeutics has requested an end-of-phase 2 meeting with the FDA to discuss plans for a phase 3 trial and address trial design questions. The company also met with patient advocacy groups, patients, and physicians to provide comments on how to interpret the data. Although this phase 2 trial was not intended to provide significant findings, hence the small sample, the study helped investigators with their primary objective of the study: building the groundwork to inform the next direction of this research.

“This would probably be one of the first drugs that is a stimulant that is being used in idiopathic, idiopathic hypersomnia,” Quartel said. This kind of is a bit different, right? So the different treatment modalities available do very different things, so this just provides patients and physicians with an alternative treatment modality that may be preferential for certain patients.”

References
^{Zevra Therapeutics Announces Positive Final Results from Phase 2 Clinical Trial of KP1077 For Idiopathic Hypersomnia At SLEEP 2024 Annual Meeting. Zevra Therapeutics. June 3, 2024. https://investors.zevra.com/news-releases/news-release-details/zevra-therapeutics-announces-positive-final-results-phase-2. Accessed July 19, 2024.}