In the Journals

Solriamfetol improves wakefulness, sleepiness in obstructive sleep apnea

Among patients with obstructive sleep apnea and excessive daytime sleepiness, solriamfetol significantly increased wakefulness and reduced sleepiness with mostly mild or moderate adverse events, according to results from the TONES 3 study published in the American Journal of Respiratory and Critical Care Medicine.

For the double-blind, randomized, placebo-controlled, parallel-group phase 3 study, Paula K. Schweitzer, PhD, research director at the Sleep and Medicine Research Center at St. Luke’s Hospital in Chesterfield, Missouri, and colleagues randomly assigned 476 patients to 37.5 mg, 75 mg, 150 mg or 300 mg once-daily oral solriamfetol (Sunosi, Jazz Pharmaceuticals) or placebo for 12 weeks. The prespecified efficacy analysis included 459 patients.

Efficacy and safety outcomes

For Maintenance of Wakefulness Test (MWT) sleep latency at week 1, the least squares mean change from baseline ranged from 4.2 to 13.3 minutes for the 37.5-mg and 300-mg doses, respectively, and were greater than the 0.4-minute change seen with placebo. These increases were maintained throughout the study, and at weeks 4 and 12, all solriamfetol doses vs. placebo resulted in greater improvements (P < .05).

Solriamfetol was also linked to dose-dependent decreases in Epworth Sleepiness Scale (ESS) score at week 1 that remained stable through week 12. All doses resulted in greater decreases than with placebo at all time points, except for the 37.5-mg dose at week 8. Further, ESS scores decreased by more than 7 points with the 150-mg and 300-mg doses (P < .0001) vs. only 3.3 points with placebo.

Additionally, at week 12, fewer patients in the placebo group had mean MWT sleep latency of 20 minutes or more (23.4%) when compared with those treated with solriamfetol 37.5 mg (34%), 75 mg (53.6%), 150 mg (62.5%) and 300 mg (65.7%). Similarly, as compared with 37.7% of patients in the placebo group, the percentage of patients with ESS scores of 10 or less ranged from 51.8% to 73% with solriamfetol.

Patient Global Impression of Change (PGI-C) — a key secondary endpoint — improved in only 49.1% of the placebo group vs. 72.4% of the solriamfetol 75-mg (P < .05), 89.7% of the 150-mg (P < .0001) and 88.7% of the 300-mg groups (P < .0001). Again, the effects were dose-dependent and evident at week 1.

Notably, adverse events were common — occurring in 47.9% patients assigned placebo and 67.9% of those assigned solriamfetol, with the most commonly reported events with the study drug being headache (10.1%), nausea (7.9%), decreased appetite (7.6%), anxiety (7%) and nasopharyngitis (5.1%). Five patients experienced serious adverse events, including two in the placebo group and three in the solriamfetol group, none of which were considered related to the study drug, according to the researchers.

At baseline, 69.7% of the placebo group and 73.5% of the solriamfetol group were using primary OSA therapy. Of these patients on OSA therapy, 91.6% assigned placebo and 92.7% assigned solriamfetol were using positive airway pressure. The remainder of patients were using another type of device or the therapy was not specified.

Future concerns

In an accompanying editorial, Vishesh K. Kapur, MD, MPH, from the University of Washington School of Medicine, and Lucas M. Donovan, MD, MS, also from the University of Washington School of Medicine and the Veterans Affairs Puget Sound Health Care System, expressed concern that the study excluded patients who may have other reversible causes of hypersomnia.

Treatment with solriamfetol would therefore unnecessarily expose patients to the unknown long-term consequences of the medication and the potential adverse effects of untreated OSA and sleep deprivation, they noted.

“We propose that a more systematic and robust approach to addressing reversible causes of persistent hypersomnia may yield more benefit than the liberal use of alerting agents. In this regard, the development of a standardized approach to evaluate and address persistent hypersomnia would be helpful,” Kapur and Donovan wrote. “It is time to consider the development of a behavioral program to address reversible causes of persistent sleepiness in patients with OSA. Within this framework, patients with OSA who have significant sleepiness after comprehensive clinical evaluation and intervention would be well-suited to receive alerting therapy. Among these patients, solriamfetol may provide particular value for those not adequately addressed by less expensive and more extensively evaluated alerting agents.” – by Melissa Foster

Disclosures: This study was funded by Jazz Pharmaceuticals. Donovan reports he has received grants from ASPIRe Educational/Research Fellowship. Kapur reports he is a co-author on a submitted abstract based on research performed by the Sleep Apnea Patient Centered Outcomes Network, which has received funding from Jazz Pharmaceuticals. Schweitzer reports she has received grants and nonfinancial support from Jazz Pharmaceuticals, nonfinancial support from INC Research (now Syneos Health), nonfinancial support from The Curry Rockefeller Group, LLC and grants from Jazz Pharmaceuticals, Philips Respironics and NightBalance.

Among patients with obstructive sleep apnea and excessive daytime sleepiness, solriamfetol significantly increased wakefulness and reduced sleepiness with mostly mild or moderate adverse events, according to results from the TONES 3 study published in the American Journal of Respiratory and Critical Care Medicine.

For the double-blind, randomized, placebo-controlled, parallel-group phase 3 study, Paula K. Schweitzer, PhD, research director at the Sleep and Medicine Research Center at St. Luke’s Hospital in Chesterfield, Missouri, and colleagues randomly assigned 476 patients to 37.5 mg, 75 mg, 150 mg or 300 mg once-daily oral solriamfetol (Sunosi, Jazz Pharmaceuticals) or placebo for 12 weeks. The prespecified efficacy analysis included 459 patients.

Efficacy and safety outcomes

For Maintenance of Wakefulness Test (MWT) sleep latency at week 1, the least squares mean change from baseline ranged from 4.2 to 13.3 minutes for the 37.5-mg and 300-mg doses, respectively, and were greater than the 0.4-minute change seen with placebo. These increases were maintained throughout the study, and at weeks 4 and 12, all solriamfetol doses vs. placebo resulted in greater improvements (P < .05).

Solriamfetol was also linked to dose-dependent decreases in Epworth Sleepiness Scale (ESS) score at week 1 that remained stable through week 12. All doses resulted in greater decreases than with placebo at all time points, except for the 37.5-mg dose at week 8. Further, ESS scores decreased by more than 7 points with the 150-mg and 300-mg doses (P < .0001) vs. only 3.3 points with placebo.

Additionally, at week 12, fewer patients in the placebo group had mean MWT sleep latency of 20 minutes or more (23.4%) when compared with those treated with solriamfetol 37.5 mg (34%), 75 mg (53.6%), 150 mg (62.5%) and 300 mg (65.7%). Similarly, as compared with 37.7% of patients in the placebo group, the percentage of patients with ESS scores of 10 or less ranged from 51.8% to 73% with solriamfetol.

Patient Global Impression of Change (PGI-C) — a key secondary endpoint — improved in only 49.1% of the placebo group vs. 72.4% of the solriamfetol 75-mg (P < .05), 89.7% of the 150-mg (P < .0001) and 88.7% of the 300-mg groups (P < .0001). Again, the effects were dose-dependent and evident at week 1.

Notably, adverse events were common — occurring in 47.9% patients assigned placebo and 67.9% of those assigned solriamfetol, with the most commonly reported events with the study drug being headache (10.1%), nausea (7.9%), decreased appetite (7.6%), anxiety (7%) and nasopharyngitis (5.1%). Five patients experienced serious adverse events, including two in the placebo group and three in the solriamfetol group, none of which were considered related to the study drug, according to the researchers.

PAGE BREAK

At baseline, 69.7% of the placebo group and 73.5% of the solriamfetol group were using primary OSA therapy. Of these patients on OSA therapy, 91.6% assigned placebo and 92.7% assigned solriamfetol were using positive airway pressure. The remainder of patients were using another type of device or the therapy was not specified.

Future concerns

In an accompanying editorial, Vishesh K. Kapur, MD, MPH, from the University of Washington School of Medicine, and Lucas M. Donovan, MD, MS, also from the University of Washington School of Medicine and the Veterans Affairs Puget Sound Health Care System, expressed concern that the study excluded patients who may have other reversible causes of hypersomnia.

Treatment with solriamfetol would therefore unnecessarily expose patients to the unknown long-term consequences of the medication and the potential adverse effects of untreated OSA and sleep deprivation, they noted.

“We propose that a more systematic and robust approach to addressing reversible causes of persistent hypersomnia may yield more benefit than the liberal use of alerting agents. In this regard, the development of a standardized approach to evaluate and address persistent hypersomnia would be helpful,” Kapur and Donovan wrote. “It is time to consider the development of a behavioral program to address reversible causes of persistent sleepiness in patients with OSA. Within this framework, patients with OSA who have significant sleepiness after comprehensive clinical evaluation and intervention would be well-suited to receive alerting therapy. Among these patients, solriamfetol may provide particular value for those not adequately addressed by less expensive and more extensively evaluated alerting agents.” – by Melissa Foster

Disclosures: This study was funded by Jazz Pharmaceuticals. Donovan reports he has received grants from ASPIRe Educational/Research Fellowship. Kapur reports he is a co-author on a submitted abstract based on research performed by the Sleep Apnea Patient Centered Outcomes Network, which has received funding from Jazz Pharmaceuticals. Schweitzer reports she has received grants and nonfinancial support from Jazz Pharmaceuticals, nonfinancial support from INC Research (now Syneos Health), nonfinancial support from The Curry Rockefeller Group, LLC and grants from Jazz Pharmaceuticals, Philips Respironics and NightBalance.