Phase 3 Trial Shows Solriamfetol Is Effective in Treating Narcolepsy and OSA

Solriamfetol has been shown to have both long- and short-term efficacy in individuals with excessive sleepiness in narcolepsy and obstructive sleep apnea (OSA), decreasing sleep tendencies, increasing wakefulness, and improving overall quality of life, study results published in the Nature and Science of Sleep show.

The TONES trials were split into 5 different arms: trials 1 and 2 for narcolepsy, trial 3 for OSA, and trials 4 and 5 for both OSA and narcolepsy. Each was scored with a maintenance of wakefulness test (MWT) mean sleep latency and the mean score of the Epworth Sleepiness Scale (ESS).

The first trial showed that individuals with narcolepsy treated with either a 150- or 300-mg dose of solriamfetol showed significant improvements within 40 minutes of their MWT and ESS scores compared with the placebos.

Investigators also determined that a score greater than a 25% reduction in ESS scores could be useful to identify individuals with narcolepsy who respond to solriamfetol.

In the second trial, individuals with narcolepsy were randomly given a 75-, 150-, or 300-mg dose of solriamfetol or the placebo to be taken once a day. The MWT scores improved in the 150- and 300-mg groups compared with the placebo, but the scores for the 75-mg group did not. The ESS scores significantly improved for all 3 doses compared with the placebo.

Solriamfetol also proved to be effective in treating excessive sleep for individuals with narcolepsy. The ESS scores were less than 10 for 15.5% of individuals in the placebo group, 30.5% in the 75-mg group, and 49.2% in the 300-mg group. The 150-mg group’s score decreased from 17 to 11.1 at week 12.

In trial 3, OSA participants randomly received 3.5, 75-, 150, or 300 mg of solriamfetol or a placebo to be taken once a day. The MWT was significantly greater at week 12 for individuals taking 75, 150, and 300 mg, than the placebo, but the 37.5-mg dose did not show significant differences.

About 70% of individuals in the 150- and 300-mg groups had ESS scores less than 10 compared with 37.7% of the placebo group.

For individuals with excessive sleeping, the quality of life and work productivity improved for individuals compared with the placebo.

Trials 4 and 5 were withdrawal trials. Individuals who experienced a clinical response were randomized to continue the dosage or switch to the placebo. The group that switched to the placebo had worse ESS scores than those who continued the dosage.

About 43% of individuals with narcolepsy and 84.5% of individuals with OSA reported an ESS of less than 10 at the conclusion of trial 5.

In trials 2, 3, and 4, solriamfetol had similar safety and tolerability results that included acute cholecystitis, anxiety, bile duct obstruction, conversion disorder, and non-cardiac chest pain. In the last study, the withdrawal symptoms included anxiety at 1.1% and depression, dry mouth, headache, insomnia, irritability, and nausea at less than 1% each.

The study included 2 12-week, double-blind trials with individuals with narcolepsy or OSA and then 2 withdrawal trials consisting of a 6-week double-blind trial for individuals with OSA and a 52-week open-label trial for individuals with narcolepsy or OSA.

The FDA’s approval was based on the results from the TONES phase 2 trials.

Reference

Abad V. Profile of solriamfetol in the management of excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea: focus on patient selection and perspectives. Nat Sci Sleep. 2021;13:75-91.doi:10.2147/NSS.S245020