Phase 2 Data Shows KP1077 Meaningfully Improves Idiopathic Hypersomnia Symptoms

A phase 2 study showed KP1077 (serdexmethylphenidate or SDX) meaningfully improves excessive daytime sleepiness, sleep inertia, brain fog, and patient-reported outcomes in idiopathic hypersomnia.

Zevra Therapeutics announced the positive data on June 3, 2024, during SLEEP 2024, the 38th annual meeting of the Associated Professional Sleep Societies. The efficacy and safety of KP1077 were evaluated in a phase 2, proof-of-concept, placebo-controlled, double-blind, clinical trial with a small sample size of 50 patients. Participants were split into groups of dosing once a day and dosing twice a day with 25 per arm. After a 2:1 randomization, the placebo groups only had 8 patients.

“Single-digit number of placebo groups give you a bit of information, but really does not allow you to make overall statements as did it work, or did it not work?” Adrian Quartel, MD, the Chief Medical Officer of Zevra Therapeutics, told HCPLive.

He explained the trial was never intended to produce significant findings—it was to provide information on how to best design a phase 3 trial. The study helped inform them they might need to adjust the learning phase length, either shortening or elongating it.

“Those are really the answers that we were looking for, or the answers that we questioned that we had that we hoped we could find meaningful answers to, and the trial has provided us with all that information,” Quartel said.

Although the study was not designed to bring statistical significance, investigators still sought to demonstrate the safety and tolerability of KP1077 for idiopathic hypersomnia. The investigators examined the secondary endpoints which were change from baseline in the 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.

Quartel said the study found significantly clinically meaningful improvements in excessive daytime sleepiness and brain fog. Sleep inertia also improved, but the clinical meaningfulness still needs to be evaluated.

The study also demonstrated KP1077 has a clean safety profile and is absorbed in a different way than other stimulants. Investigators found no cardiovascular signs. Some participants experienced transient insomnia, but only for a little while as they adjusted to the treatment.

“[These participants] had some periods of insomnia during the first or the second night, and after that, [it] disappeared,” Quartel said. “There is no concern in regards to insomnia being a safety concern for the use of this product in idiopathic hypersomnia.”

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.}