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New drug shows promise in patients with narcolepsy, sleep apnea

Jazz Pharmaceuticals announced that its selective dopamine and norepinephrine reuptake inhibitor, known as JZP-110, showed positive efficacy in adult patients with excessive sleepiness associated with both obstructive sleep apnea and narcolepsy, according to presentations from Sleep 2017, the Annual Meeting of the Associated Professional Sleep Societies.

These findings come from data collected from four studies included in the TONES phase 3 program, one of which assessed excessive sleepiness in adult patents with narcolepsy (TONES 2) and two of which evaluated excessive sleepiness in adult patients with obstructive sleep apnea (OSA; TONES 3 and TONES 4).

“These studies suggest that JZP-110 could provide an important treatment option for patients with excessive sleepiness,” Karen Smith, MD, PhD, executive vice president of research and development, and chief medical officer of Jazz Pharmaceuticals, said in a related press release. “It also underscores our commitment to making significant research and development investments to find innovative treatments for unmet medical needs in sleep medicine.”

To assess the change in mean sleep latency from baseline to week 12, the phase 3 TONES 2 study randomly assigned 239 patients with excessive sleepiness in narcolepsy to placebo or 300-mg, 150-mg or 75-mg doses of JZP-110.

Analysis showed that JZP-110 150-mg and 300-mg doses significantly increased mean sleep latency compared with placebo at week 12 as measured by the maintenance of wakefulness test (MWT). These effects showed significance by week 1 and continued throughout the study period (P < .0001). Epworth Sleepiness Scale (ESS) scores for JZP-110 significantly decreased compared with placebo at all doses by week 12, with the 75-mg dose reaching statistical significance. A higher percentage of patients reported improvement in their overall condition after taking JZP-110 than those taking placebo.

“This study demonstrated that JZP-110 could be an important treatment option for patients who suffer from excessive sleepiness as a result of narcolepsy,” Smith said in a release. “It also further highlights our deep commitment to our sleep therapeutic area and our significant investment in research and development to bring innovative treatments to patients with important unmet medical needs.”

The two studies that examined patients with excessive sleepiness from OSA, TONES 3 and 4, also showed improvements with JZP-110. TONES 3, a 12-week, randomized study, compared the safety and efficacy of JZP-110 at 300 mg, 150 mg, 75 mg and 37.5 mg with placebo in 476 patients with OSA to determine change in mean sleep latency.

JZP-110 demonstrated statistically significant improvement of mean sleep latency on the MWT and the ESS from baseline to week 12 at all doses compared with placebo among patients with OSA. The inhibitor increased the mean MWT sleep latency by more than 10 minutes at all time points at the 150-mg and 300-mg doses, and decreased mean ESS scores by more than 7 points at the same doses, at week 12. Also, roughly 90% of patients experienced overall improvement from the 150-mg and 300-mg doses at study end, and all patients reported significant overall improvement compared with placebo at all doses excluding 37.5 mg, the researchers reported.                   

The TONES 4 study, composed of a 2-week, flexible dose-titration phase followed by 2 weeks of stable-dose treatment, randomly allocated 174 patients with OSA to a maximum tolerated dose over a 2-week period, with 157 patients continuing that dosage for 2 weeks in the stable-dose phase. Analysis revealed that patients who completed the 4-week treatment and remained on JZP-110 did not show loss of efficacy compared with those randomly assigned to placebo and continued to show improvement on the MWT and ESS during the double-blind withdrawal phase (weeks 4 to 6).

“The results with JZP-110 show significant increase in a patients’ ability to stay awake and decreased patients’ subjective levels of sleepiness compared to placebo, in a rather customary practice setting,” Kingman Strohl, MD, professor of medicine at the University Hospitals Case Medical Center and Case School of Medicine, said in a release. – by Savannah Demko

References:

Schweitzer PK, et al. Abstract 0641. Presented at: Sleep 2017, the Annual Meeting of the Associated Professional Sleep Societies; June 3-7, 2017; Boston.

Strollo PJ, et al. Abstract 0644. Presented at: Sleep 2017, the Annual Meeting of the Associated Professional Sleep Societies; June 3-7, 2017; Boston.

Thorpy MJ, et al. Abstract 0675. Presented at: Sleep 2017, the Annual Meeting of the Associated Professional Sleep Societies; June 3-7, 2017; Boston.

Disclosure: Smith reports being an executive vice president at Jazz Therapeutics. All research was supported by Jazz Therapeutics. Healio Family Medicine was unable to determine Strohl's relevant financial disclosures prior to publication.