Solriamfetol Demonstrates Safety, Efficacy for Wakefulness in 1-Year Extension Trial

Solriamfetol, a novel oral medication recently approved by the FDA to promote wakefulness in adults with obstructive sleep apnea (OSA) or narcolepsy, was well-tolerated and maintained its efficacy during a one-year, open-label extension trial. A subset of participants who underwent a two-week randomized, placebo-controlled withdrawal phase provided further evidence of the drug’s safety and efficacy.

Results of this just-completed study were detailed in a May 9 platform presentation at the 2019 annual meeting of the American Academy of Neurology (AAN) by Cleveland Clinic neurologist Nancy Foldvary-Schaefer, DO, MS, first author of the multicenter study, which was designated on the meeting’s “Abstracts of Distinction” by the AAN.

“This extension trial further supports the safety and efficacy of solriamfetol for excessive daytime sleepiness in patients with obstructive sleep apnea or narcolepsy,” says Dr. Foldvary-Schaefer, who directs Cleveland Clinic’s Sleep Disorders Center. “This is good news for an important novel therapy in an area that has not had a new drug approved in nearly 15 years.”

The FDA approved solriamfetol (Sunosi™), a selective dopamine and norepinephrine reuptake inhibitor, in March 2019 to treat adults with excessive daytime sleepiness associated with narcolepsy or OSA, based on separate OSA and narcolepsy randomized controlled trials that lasted up to six months.

Extension study at a glance

Patients with narcolepsy or OSA who participated in prior studies testing solriamfetol were eligible for the extension trial. The 643 participants (226 with narcolepsy and 417 with OSA) underwent two weeks of titration of solriamfetol, followed by an open-label maintenance phase of up to 50 weeks. Only during the initial 14 weeks of the study could individual adjustments be made to the dosage, based on adverse effects or a desire for greater therapeutic effect.

Efficacy was determined using two patient self-reporting tools — the Epworth Sleepiness Scale (ESS) and the Patient Global Impression of Change (PGI-C) — as well as the Clinician Global Impression of Change (CGI-C).

Throughout the trial, participants were found to have sustained improvements in all scores. “We found very little fluctuation of efficacy over time,” says Dr. Foldvary-Schaefer. “Because we could not increase dosages after the initial period, this indicated that drug tolerance did not appear to be an issue.”

Insights from the withdrawal phase

The second component of the trial — a randomized, double-blind withdrawal phase — involved a subset of participants who, after six months of solriamfetol treatment, either continued on the drug (n = 139) or were abruptly switched to placebo (n = 141) for two weeks.

From the beginning to the end of this phase, the least-squares mean change in ESS score was significantly less in those who continued solriamfetol compared with those taking placebo (1.6 vs. 5.3; P < 0.0001). Likewise, PGI-C and CGI-C scores were significantly better in participants who remained on solriamfetol than in those switched to placebo (P < 0.0001 for each score).

“It did not take long to lose benefits of the drug for those who were switched to placebo,” Dr. Foldvary-Schaefer observes. “And no safety or tolerability concerns were raised for abrupt withdrawal.”

Safety findings echo pivotal trials

The trial identified the following as common adverse events (i.e., occurring in at least 5% of participants): headache, nausea, nasopharyngitis, insomnia, dry mouth, anxiety, reduced appetite and upper respiratory tract infection. At least one serious adverse event occurred in 27 study participants (4.2%).

According to Dr. Foldvary-Schaefer, this safety profile is consistent with the earlier placebo-controlled studies of solriamfetol and is typical of other wake-promoting agents. She adds that side effects are often transient and/or resolve with dose adjustment.

Launch expected this year

Solriamfetol is expected to become commercially available later in 2019, pending a final scheduling decision by the U.S. Drug Enforcement Administration. It will be offered as a once-daily treatment at doses of 75 mg or 150 mg for either condition, as well as a 37.5-mg option for OSA.

Dr. Foldvary-Schaefer warns that solriamfetol is not designed to be a substitute for continuous positive airway pressure therapy for OSA, which remains the standard treatment for breathing fluctuations that occur during sleep.

“I’m looking forward to having a drug with a novel action for my patients with OSA and narcolepsy,” she adds. “This will provide a new option to treat debilitating daytime sleepiness that impacts occupational and academic productivity and quality of life.”

The extension trial was supported by Jazz Pharmaceuticals, which markets solriamfetol.