FDA Accepts Solriamfetol Application for Excessive Sleepiness

March 2, 2018

The FDA has accepted an application for solriamfetol as a treatment for excessive sleepiness associated with narcolepsy or obstructive sleep apnea, with a PDUFA action date set for December 20, 2018.

Karen Smith, MD, PhD

The FDA has accepted an application for solriamfetol (JZP-110) as a treatment for excessive sleepiness associated with narcolepsy or obstructive sleep apnea (OSA), according to Jazz Pharmaceuticals, the company developing the drug. Under the Prescription Drug User Fee Act (PDUFA), the FDA will decide on the application by December 20, 2018.

The application for solriamfetol, a selective dopamine norepinephrine reuptake inhibitor, was based on improvements in wakefulness in the TONES clinical trial program, which consisted of 4 phase III clinical trials. In the first study, TONES 2, solriamfetol was explored in narcolepsy. TONES 3 and 4 examined the drug in OSA, and TONES 5 looked at maintenance treatment in OSA and narcolepsy.

In the TONES 5 trial, after approximately 6 months of maintenance treatment, a randomized 2-week placebo-controlled phase was performed. In this phase, there was a -3.7 Least Squares (LS) mean change in Epworth Sleepiness Scale (ESS) with solriamfetol versus placebo (95% CI, -4.80 to -2.65; P <.0001). The mean LS was 1.6 with solriamfetol compared with 5.3 with placebo. An open-label portion of the study demonstrated long-term efficacy with solriamfetol that lasted up to 1 year.

"We believe this medicine will provide a meaningful option for patients living with excessive sleepiness due to narcolepsy or OSA, and we look forward to working with the FDA during the review process for solriamfetol," Karen Smith, MD, PhD, executive vice president, research and development and chief medical officer at Jazz Pharmaceuticals, said in a statement. "Jazz continues to invest in ongoing research, education and advocacy on behalf of the sleep community, including studying solriamfetol for the treatment of excessive sleepiness in other areas of unmet need, such as Parkinson's disease."

In the TONES 2 study in narcolepsy, patients were randomized to placebo (n = 60) or solriamfetol across dose levels at 300 mg (n = 60), 150 mg (n = 60), 75 mg (n = 59). Overall, solriamfetol decreased ESS by -3.8 to -6.4 across doses. The mean change for placebo was -1.6. Mean sleep latency on maintenance of wakefulness test (MWT) was 12.3 minutes at the highest dose to 4.7 minutes at the lowest. For placebo, the mean latency was 2.1 minutes.

For the TONES 3 trial, patients with OSA were randomized across 5 arms for 12 weeks of treatment: 119 in the placebo group and solriamfetol at doses of 37.5 mg (n = 59), 75 mg (n = 61), 150 mg (n = 118), and 300 mg (n = 119). The mean sleep latency was 13 minutes at the highest dose of solriamfetol and 4.7 at the lowest. In the placebo group, it was 0.2 minutes. The ESS was -7.9 in the highest dose arm and -5.1 with the lowest versus -3.3 with placebo.

In the TONES 4 trial in OSA, 174 patients were treated in a 2-week flexible-dose titration phase followed by 2-weeks of stable dose treatment, which was received by 157 patients. After this phase, those in solriamfetol arm continued to receive treatment. The mean sleep latency by MWT was -1.0 minute with solriamfetol compared with -12.1 minutes for placebo. The ESS was -0.1 with solriamfetol versus 4.5 for placebo.

"As a leader in sleep medicine, Jazz is focused on addressing the needs of the sleep community through the research and development of new treatment options, and we 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, said when findings from TONES 5 were presented in June 2018 at the 32nd Annual Meeting of the Associated Professional Sleep Societies.

"If approved by the U.S. 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 U.S. in nearly 10 years," Black said.

In the TONES 5 study, the most frequent treatment-emergent serious adverse events (AEs) with solriamfetol, which were experienced by 4.2% of patients, were headache, nausea, insomnia, nasopharyngitis, dry mouth, and anxiety. The other TONES studies showed little to no serious AEs.

Solriamfetol continues to be developed for other forms of excessive sleepiness, including a phase II study for patients with Parkinson disease. Findings from this study are anticipated before the end of the year (NCT03037203).