BALTIMORE — Daily treatment with the wake-promoting drug solriamfetol (Jazz Pharmaceuticals) reduced excessive sleepiness (ES) in patients with narcolepsy or obstructive sleep apnea (OSA) for up to 1 year in the TONES 5 study.
The open-label phase 3 study showed "durable effects of solriamfetol without major side effects," study investigator Atul Malhotra, MD, from the University of California San Diego, told delegates attending SLEEP 2018: 32nd Annual Meeting of the Associated Professional Sleep Societies.
Solriamfetol (JZP-110) is an investigational selective dopamine and norepinephrine reuptake inhibitor with robust waking-promoting effects in development for treatment of ES in adults with narcolepsy, OSA, and Parkinson's disease.
The neurotransmitter profile of solriamfetol differs from that of drugs currently on the market to treat ES, such as modafinil.
In earlier 6- and 12-week studies, solriamfetol was effective for treatment of ES in patients with narcolepsy and OSA. The TONES 5 study was a longer-term study testing the safety and maintenance of efficacy of the drug.
Patients with ES due to narcolepsy or OSA, including those who had completed prior studies with solriamfetol, began treatment with solriamfetol in the 2-week titration phase (75 mg/d to start, with titration up to 150 or 300 mg) followed by a maintenance phase of up to 52 weeks. A subset of patients participated in a 2-week placebo-controlled randomized withdrawal phase after about 6 months of treatment.
A total of 643 patients (226 with narcolepsy; 417 with OSA) were administered solriamfetol and included in the safety population, and 458 completed the study. A total of 282 patients were entered into the randomized withdrawal phase, and 280 completed this phase (139 receiving solriamfetol and 141 receiving placebo), representing the modified intent-to-treat population.
The primary endpoint in the randomized withdrawal phase was change in Epworth Sleepiness Scale (ESS) from beginning to end of the randomized withdrawal. Secondary endpoints were Patient Global Impression of Change (PGI-C) and Clinician Global Impression of Change (CGI-C).
Favorable Safety, Efficacy Profile
At the end of the RW phase, patients who received solriamfetol remained improved, whereas those who were switched to placebo worsened. The least squares mean change in ESS score was 1.6 with solriamfetol compared with 5.3 with placebo, resulting in a least squares mean difference of –3.7 (95% confidence interval, –4.80 to –2.65; P < .0001).
Results were similar in subgroup analyses of patients with OSA and patients with narcolepsy.
For both secondary endpoints, significantly greater percentages of patients who were switched to placebo were rated by their physicians (CGI-C) and themselves (PGI-C) as worse in their overall condition at the end of the randomized withdrawal phase compared with the solriamfetol group (both P < .0001).
Long-term maintenance of efficacy was also demonstrated during the open-label period for up to 1 year by sustained reductions in mean ESS scores and improvements on the PGI-C and CGI-C scales, Atul Malhotra reported.
"The safety profile was consistent with prior placebo-controlled studies of solriamfetol," he said. The most common treatment-emergent serious adverse events (≥5%) with solriamfetol were headache, nausea, insomnia, nasopharyngitis, dry mouth, and anxiety; 4.2% patients experienced one or more serious treatment-emergent adverse events. There was one death due to sepsis in a 70-year-old immunosuppressed male with OSA taking 300 mg solriamfetol. The death was considered by investigators as unrelated to the drug.
"[W]e are pleased that the results of this long-term study are consistent with the safety and efficacy that we have seen across the breadth of our clinical program for solriamfetol," Jed Black, MD, senior vice president, sleep and CNS medicine at Jazz Pharmaceuticals and adjunct professor, Stanford Center for Sleep Sciences and Medicine in California, said in a statement.
"If approved by the US Food and Drug Administration, solriamfetol would offer patients the first new chemical entity for the treatment of excessive sleepiness in narcolepsy and OSA in the US in nearly 10 years."
Commenting on the study for Medscape Medical News, Raman Malhotra, MD, associate professor of neurology at the Washington University Sleep Center in St Louis, Missouri, and American Academy of Sleep Medicine board member, said, "We just don't have a lot of medications for narcolepsy so anytime you can add a new drug with a different mechanism, that's exciting."
The study was supported by Jazz Pharmaceuticals. Seven study authors have disclosed financial relationships with the company. Raman Malhotra has disclosed no relevant financial relationships.
SLEEP 2018: 32nd Annual Meeting of the Associated Professional Sleep Societies. Abstracts 0620 and 0621. Presented June 5, 2018.
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Cite this: New Drug for Narcolepsy, Sleep Apnea on the Horizon - Medscape - Jun 12, 2018.