Jazz Pharmaceuticals plc presented the positive efficacy results from its global multicenter study of JZP-110 in adult patients with excessive sleepiness associated with narcolepsy. The data were presented in a poster session at SLEEP 2017 in Boston.
“Excessive sleepiness is a significant and serious symptom for patients with narcolepsy,” says Karen Smith, MD, PhD, executive vice president of research and development and chief medical officer of Jazz Pharmaceuticals, in a release. “This study demonstrated that JZP-110 could be an important treatment option for patients who suffer from excessive sleepiness as a result of narcolepsy. 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.”
Michael J. Thorpy, MD, ChB, professor of clinical neurology, The Saul R. Korey Department of Neurology, Albert Einstein College of Medicine, says, “This study demonstrated statistically significant effects of both 150 mg and 300 mg doses of JZP-110 on the co-primary endpoints of change in mean sleep latency on the Maintenance of Wakefulness Test and change in Epworth Sleepiness Scale score from baseline to week 12. The effects seen in this study were maintained over the full 12 weeks of the study. This is a potentially important development for patients with narcolepsy who experience excessive sleepiness.”
The Treatment of OSA and Narcolepsy Excessive Sleepiness (TONES) Phase 3 program is comprised of four studies, one study evaluating excessive sleepiness in adult patients with narcolepsy (TONES 2), two studies evaluating excessive sleepiness in adult patients with OSA (TONES 3 and TONES 4), and an open-label, long-term safety and maintenance of efficacy study (TONES 5) in the treatment of excessive sleepiness in patients with narcolepsy or OSA.
About the Global Phase 3 TONES 2 Study
TONES 2 was a 12-week, 4-arm, parallel-group, double-blind, placebo-controlled, randomized Phase 3 study that evaluated the safety and efficacy of JZP-110 in adults with excessive sleepiness in narcolepsy. Patients (N=239) were randomized 1:1:1:1 to JZP-110 300 mg (n=60), 150 mg (n=60), 75 mg (n=59), and placebo (n=60). The co-primary endpoints were the change in mean sleep latency on the Maintenance of Wakefulness Test (MWT) and in the Epworth Sleepiness Scale (ESS) score from baseline to week 12. The key secondary endpoint was the percentage of patients who reported improvement on the Patient Global Impression of Change (PGIc) scale, a patient-reported measure in overall condition from baseline to week 12.
In patients with narcolepsy, JZP-110 150 mg and 300 mg doses significantly increased mean sleep latency relative to placebo at week 12 on the MWT and these effects were observed as early as week one and continued throughout the 12 weeks of the study (p<0.0001). JZP-110 significantly decreased ESS scores relative to placebo at all doses at week 12 (p<0.0001 for 150 mg and 300 mg doses and p<0.05 for 75 mg dose). The JZP-110 75 mg dose reached statistical significance on the co-primary endpoint of the ESS, but not the MWT. On the key secondary endpoint of PGIc, JZP-110 significantly increased the percentage of patients who reported improvement in their overall condition at all doses relative to placebo at week 12 (p<0.0001 for 150 mg and 300 mg doses and nominal p-value of p<0.05 at the 75 mg dose as the co-primary endpoint of MWT was not met at this dose).
The modified intent-to-treat (mITT) population for the efficacy analysis consisted of 231 patients.
The estimated changes from baseline to week 12 were:
The safety and tolerability of JZP-110 were consistent with the previous Phase 2 studies in patients with narcolepsy. Of the 239 subjects randomized, 195 completed the 12-week treatment. Ten patients discontinued due to treatment emergent adverse events. Discontinuations due to treatment emergent adverse events were greater than placebo (n=1, 1.7%) in the JZP-110 150 (n=3, 5.1%) and 300 mg (n=5, 8.5%) groups, and the same in the JZP-110 75 mg dose group (n=1, 1.7%). The most commonly reported treatment emergent adverse events across all doses of JZP-110 (occurring >5% of patients across all JZP-110 groups) were headache, nausea, decreased appetite, nasopharyngitis, dry mouth, and anxiety. There was one subject with two serious adverse events (non-cardiac chest pain and anxiety) on JZP-110 that were considered not treatment related as assessed by the investigator.