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The therapy remains effective during long-term treatment and improves functioning and work productivity.
BALTIMORE—Solriamfetol effectively reduces excessive sleepiness in patients with narcolepsy, regardless of whether they also have cataplexy, according to research described at the 32nd Annual Meeting of the Associated Professional Sleep Societies. The drug also improves work productivity and reduces activity impairment outside of work in this population. The molecule’s efficacy is maintained during one year of treatment in patients with narcolepsy or obstructive sleep apnea (OSA), and solriamfetol generally is safe and well tolerated, said the researchers.
A Reanalysis of Phase III Data
Solriamfetol is a selective dopamine and norepinephrine reuptake inhibitor that promoted wakefulness in patients with narcolepsy in a large phase III trial. Investigators presented the results of three new studies of solriamfetol during the meeting. In the first study, Yves Dauvilliers, MD, PhD, a neurologist at Gui-de-Chauliac Hospital in Montpellier, France, and colleagues reanalyzed the data from the phase III trial to assess the drug’s efficacy in subgroups of patients with and without cataplexy. 
Eligible patients were adults with type 1 or type 2 narcolepsy, a baseline Maintenance of Wakefulness Test (MWT) result of less than 25 minutes, and an Epworth Sleepiness Scale (ESS) score of 10 or greater. Patients were randomized in equal groups to placebo or a 75-mg, 150-mg, or 300-mg dose of solriamfetol for 12 weeks. The primary end points were the change from baseline to week 12 in sleep latency on the MWT, the ESS, and the Patient Global Impression of Change (PGI-C) scale.
Of the 231 patients included in the analysis, 117 had cataplexy. The investigators observed no key baseline differences i
Among participants with cataplexy, the mean change in sleep latency at Week 12 was 1.8 minutes in the placebo group, 3.4 minutes in the 75-mg group, 7.9 minutes in the 150-mg group, and 10.7 minutes in the 300-mg group. Among participants without cataplexy, the mean change was 2.6 minutes in the placebo group, 6.0 minutes in the 75-mg group, 11.6 minutes in the 150-mg group, and 13.8 minutes in the 300-mg group.
The mean decrease in ESS score among patients with cataplexy at Week 12 was 1.8 points among controls, 3.1 points in the 75-mg group, 5.6 points in the 150-mg group, and 6.3 points in the 300-mg group. Among patients without cataplexy, the mean decrease was 1.5 points in controls, 4.5 points in the 75-mg group, 5.2 points in the 150-mg group, and 6.4 points in the 300-mg group.
A significantly greater percentage of patients in the 150-mg and 300-mg groups had improvement in PGI-C at Week 12, compared with controls, regardless of whether they had cataplexy. Among patients without cataplexy, a significantly greater percentage of those who received 75 mg of solriamfetol also had improvement in PGI-C at Week 12, compared with controls.
Solriamfetol Improves Work Productivity
Helene Emsellem, MD, Medical Director of the Center for Sleep and Wake Disorders in Chevy Chase, Maryland, and colleagues analyzed data from the same phase III study to examine solriamfetol’s effects on health-related quality of life and work productivity. These outcomes had been measured using the Functional Outcomes of Sleep Questionnaire, short version (FOSQ-10); the Work Productivity and Activity Impairment questionnaire for Specific Health Problem, which measures absenteeism, presenteeism (ie, working while impaired), and activity impairment outside of work; and the 36-Item Short Form Health Survey version 2 (the SF-36 v2), which includes physical and mental components. Dr. Emsellem and colleagues calculated the least-squares mean change in these measures from baseline to Week 12.
At baseline, mean FOSQ-10 total score was 12.2 among controls, 11.4 in the 75-mg group, 11.7 in the 150-mg group, and 11.4 in the 300-mg group. A normal value is approximately 18. At Week 12, FOSQ-10 score improved by 3.01 points in the 300-mg group, compared with 1.56 among controls. The difference between these groups was statistically significant. FOSQ-10 score improved by 2.39 in the 75-mg group and by 2.57 in the 150-mg group, but these results were not statistically significant.
At Week 12, the 150-mg and 300-mg doses of solriamfetol significantly reduced activity impairment outside of work, compared with placebo. In addition, the 150-mg dose significantly reduced presenteeism and a composite of absenteeism and presenteeism, compared with placebo. Solriamfetol had little effect on absenteeism, perhaps because absenteeism was uncommon at baseline, said Dr. Emsellem.
In addition, the 300-mg dose of solriamfetol significantly increased by 3.29 points the physical component summary score of the SF-36 v2, compared with placebo, which yielded a 1.06-point increase. The other doses did not significantly improve the physical component summary score. Solriamfetol did not significantly improve the mental component summary score.
Data Suggest Long-Term Efficacy
Pharmacologic treatment for narcolepsy often lasts for a long period of time, but the treatment periods in many clinical trials are comparatively short. Atul Malhotra, MD, Professor of Medicine at the University of California, San Diego, and colleagues conducted a study to examine the long-term safety and efficacy of solriamfetol.
Eligible participants had narcolepsy or OSA and had previously completed six- or 12-week trials of solriamfetol. Patients in Group A were enrolled into the long-term study immediately after having completed an earlier study, and patients in Group B were enrolled later after their completion of the earlier study.
Participants received open-label solriamfetol during a two-week titration phase. The subsequent maintenance phase lasted for 38 weeks for Group A and 50 weeks for Group B. After about six months of treatment, investigators randomized blinded patients to placebo or their assigned dose of solriamfetol for two weeks. After this randomized-withdrawal phase, all participants received solriamfetol.
The primary end point was the change in ESS score at the end of the randomized-withdrawal phase. Secondary end points were the changes in PGI-C and the Clinical Global Impression of Change (CGI-C) at the end of the randomized-withdrawal phase. The analysis was performed using a modified intention-to-treat population.
The investigators enrolled 643 participants into the study. Mean age was 49, 52% of the population was male, and mean BMI was 31.7. About 35% of participants had narcolepsy, and 65% had OSA. In all, 282 participants were assigned to the randomized-withdrawal phase, and 361 continued solriamfetol.
By the end of the randomized-withdrawal phase, ESS score had risen from 7.8 to 12.6 in the placebo group, compared with an increase from 7.3 to 8.5 in the solriamfetol group. The least-squares mean difference between the arms was –3.7.
About 65% of patients randomized to placebo reported worsening on PGI-C at the end of the randomized-withdrawal phase, compared with 28% of the solriamfetol group. Similarly, approximately 64% of patients randomized to placebo were rated as worse on the CGI-C at the end of the randomized-withdrawal phase, compared with 29% of the solriamfetol group.
At Week 40, Group A had sustained reductions in ESS score, which indicated long-term efficacy of solriamfetol. Group B had similar results during approximately one year of treatment. “There is no hint of tachyphylaxis,” said Dr. Malhotra. Improvements in PGI-C and CGI-C were stable over time.
No New Safety Concerns Emerge
The safety profile of solriamfetol in these studies was similar in participants with and without cataplexy and was consistent with that indicated by previous trials. The most common treatment-emergent adverse events in the phase III trial that Drs. Dauvilliers and Emsellem analyzed were headache, nausea, decreased appetite, nasopharyngitis, dry mouth, diarrhea, and anxiety. The rate of adverse events increased with increasing dose. More participants in the solriamfetol group discontinued the trial, compared with the placebo group. Solriamfetol did not affect BMI. Safety results were similar in Dr. Malhotra’s trial. Solriamfetol had “a durable effect without major side effects,” he said.
Jazz Pharmaceuticals, which is headquartered in Dublin, is developing solriamfetol and sponsored all three studies. The company filed a new drug application for solriamfetol with the FDA in March and expects a regulatory decision in late December.
—Erik Greb
Suggested Reading
Bogan RK, Feldman N, Emsellem HA, et al. Effect of oral JZP-110 (ADX-N05) treatment on wakefulness and sleepiness in adults with narcolepsy. Sleep Med. 2015;16(9):1102-1108.
Scrima L, Emsellem HA, Becker PM, et al. Identifying clinically important difference on the Epworth Sleepiness Scale: results from a narcolepsy clinical trial of JZP-110. Sleep Med. 2017;38:108-112.
The therapy remains effective during long-term treatment and improves functioning and work productivity.
The therapy remains effective during long-term treatment and improves functioning and work productivity.
BALTIMORE—Solriamfetol effectively reduces excessive sleepiness in patients with narcolepsy, regardless of whether they also have cataplexy, according to research described at the 32nd Annual Meeting of the Associated Professional Sleep Societies. The drug also improves work productivity and reduces activity impairment outside of work in this population. The molecule’s efficacy is maintained during one year of treatment in patients with narcolepsy or obstructive sleep apnea (OSA), and solriamfetol generally is safe and well tolerated, said the researchers.
A Reanalysis of Phase III Data
Solriamfetol is a selective dopamine and norepinephrine reuptake inhibitor that promoted wakefulness in patients with narcolepsy in a large phase III trial. Investigators presented the results of three new studies of solriamfetol during the meeting. In the first study, Yves Dauvilliers, MD, PhD, a neurologist at Gui-de-Chauliac Hospital in Montpellier, France, and colleagues reanalyzed the data from the phase III trial to assess the drug’s efficacy in subgroups of patients with and without cataplexy.
Eligible patients were adults with type 1 or type 2 narcolepsy, a baseline Maintenance of Wakefulness Test (MWT) result of less than 25 minutes, and an Epworth Sleepiness Scale (ESS) score of 10 or greater. Patients were randomized in equal groups to placebo or a 75-mg, 150-mg, or 300-mg dose of solriamfetol for 12 weeks. The primary end points were the change from baseline to week 12 in sleep latency on the MWT, the ESS, and the Patient Global Impression of Change (PGI-C) scale.
Of the 231 patients included in the analysis, 117 had cataplexy. The investigators observed no key baseline differences i
Among participants with cataplexy, the mean change in sleep latency at Week 12 was 1.8 minutes in the placebo group, 3.4 minutes in the 75-mg group, 7.9 minutes in the 150-mg group, and 10.7 minutes in the 300-mg group. Among participants without cataplexy, the mean change was 2.6 minutes in the placebo group, 6.0 minutes in the 75-mg group, 11.6 minutes in the 150-mg group, and 13.8 minutes in the 300-mg group.
The mean decrease in ESS score among patients with cataplexy at Week 12 was 1.8 points among controls, 3.1 points in the 75-mg group, 5.6 points in the 150-mg group, and 6.3 points in the 300-mg group. Among patients without cataplexy, the mean decrease was 1.5 points in controls, 4.5 points in the 75-mg group, 5.2 points in the 150-mg group, and 6.4 points in the 300-mg group.
A significantly greater percentage of patients in the 150-mg and 300-mg groups had improvement in PGI-C at Week 12, compared with controls, regardless of whether they had cataplexy. Among patients without cataplexy, a significantly greater percentage of those who received 75 mg of solriamfetol also had improvement in PGI-C at Week 12, compared with controls.
Solriamfetol Improves Work Productivity
Helene Emsellem, MD, Medical Director of the Center for Sleep and Wake Disorders in Chevy Chase, Maryland, and colleagues analyzed data from the same phase III study to examine solriamfetol’s effects on health-related quality of life and work productivity. These outcomes had been measured using the Functional Outcomes of Sleep Questionnaire, short version (FOSQ-10); the Work Productivity and Activity Impairment questionnaire for Specific Health Problem, which measures absenteeism, presenteeism (ie, working while impaired), and activity impairment outside of work; and the 36-Item Short Form Health Survey version 2 (the SF-36 v2), which includes physical and mental components. Dr. Emsellem and colleagues calculated the least-squares mean change in these measures from baseline to Week 12.
At baseline, mean FOSQ-10 total score was 12.2 among controls, 11.4 in the 75-mg group, 11.7 in the 150-mg group, and 11.4 in the 300-mg group. A normal value is approximately 18. At Week 12, FOSQ-10 score improved by 3.01 points in the 300-mg group, compared with 1.56 among controls. The difference between these groups was statistically significant. FOSQ-10 score improved by 2.39 in the 75-mg group and by 2.57 in the 150-mg group, but these results were not statistically significant.
At Week 12, the 150-mg and 300-mg doses of solriamfetol significantly reduced activity impairment outside of work, compared with placebo. In addition, the 150-mg dose significantly reduced presenteeism and a composite of absenteeism and presenteeism, compared with placebo. Solriamfetol had little effect on absenteeism, perhaps because absenteeism was uncommon at baseline, said Dr. Emsellem.
In addition, the 300-mg dose of solriamfetol significantly increased by 3.29 points the physical component summary score of the SF-36 v2, compared with placebo, which yielded a 1.06-point increase. The other doses did not significantly improve the physical component summary score. Solriamfetol did not significantly improve the mental component summary score.
Data Suggest Long-Term Efficacy
Pharmacologic treatment for narcolepsy often lasts for a long period of time, but the treatment periods in many clinical trials are comparatively short. Atul Malhotra, MD, Professor of Medicine at the University of California, San Diego, and colleagues conducted a study to examine the long-term safety and efficacy of solriamfetol.
Eligible participants had narcolepsy or OSA and had previously completed six- or 12-week trials of solriamfetol. Patients in Group A were enrolled into the long-term study immediately after having completed an earlier study, and patients in Group B were enrolled later after their completion of the earlier study.
Participants received open-label solriamfetol during a two-week titration phase. The subsequent maintenance phase lasted for 38 weeks for Group A and 50 weeks for Group B. After about six months of treatment, investigators randomized blinded patients to placebo or their assigned dose of solriamfetol for two weeks. After this randomized-withdrawal phase, all participants received solriamfetol.
The primary end point was the change in ESS score at the end of the randomized-withdrawal phase. Secondary end points were the changes in PGI-C and the Clinical Global Impression of Change (CGI-C) at the end of the randomized-withdrawal phase. The analysis was performed using a modified intention-to-treat population.
The investigators enrolled 643 participants into the study. Mean age was 49, 52% of the population was male, and mean BMI was 31.7. About 35% of participants had narcolepsy, and 65% had OSA. In all, 282 participants were assigned to the randomized-withdrawal phase, and 361 continued solriamfetol.
By the end of the randomized-withdrawal phase, ESS score had risen from 7.8 to 12.6 in the placebo group, compared with an increase from 7.3 to 8.5 in the solriamfetol group. The least-squares mean difference between the arms was –3.7.
About 65% of patients randomized to placebo reported worsening on PGI-C at the end of the randomized-withdrawal phase, compared with 28% of the solriamfetol group. Similarly, approximately 64% of patients randomized to placebo were rated as worse on the CGI-C at the end of the randomized-withdrawal phase, compared with 29% of the solriamfetol group.
At Week 40, Group A had sustained reductions in ESS score, which indicated long-term efficacy of solriamfetol. Group B had similar results during approximately one year of treatment. “There is no hint of tachyphylaxis,” said Dr. Malhotra. Improvements in PGI-C and CGI-C were stable over time.
No New Safety Concerns Emerge
The safety profile of solriamfetol in these studies was similar in participants with and without cataplexy and was consistent with that indicated by previous trials. The most common treatment-emergent adverse events in the phase III trial that Drs. Dauvilliers and Emsellem analyzed were headache, nausea, decreased appetite, nasopharyngitis, dry mouth, diarrhea, and anxiety. The rate of adverse events increased with increasing dose. More participants in the solriamfetol group discontinued the trial, compared with the placebo group. Solriamfetol did not affect BMI. Safety results were similar in Dr. Malhotra’s trial. Solriamfetol had “a durable effect without major side effects,” he said.
Jazz Pharmaceuticals, which is headquartered in Dublin, is developing solriamfetol and sponsored all three studies. The company filed a new drug application for solriamfetol with the FDA in March and expects a regulatory decision in late December.
—Erik Greb
Suggested Reading
Bogan RK, Feldman N, Emsellem HA, et al. Effect of oral JZP-110 (ADX-N05) treatment on wakefulness and sleepiness in adults with narcolepsy. Sleep Med. 2015;16(9):1102-1108.
Scrima L, Emsellem HA, Becker PM, et al. Identifying clinically important difference on the Epworth Sleepiness Scale: results from a narcolepsy clinical trial of JZP-110. Sleep Med. 2017;38:108-112.
BALTIMORE—Solriamfetol effectively reduces excessive sleepiness in patients with narcolepsy, regardless of whether they also have cataplexy, according to research described at the 32nd Annual Meeting of the Associated Professional Sleep Societies. The drug also improves work productivity and reduces activity impairment outside of work in this population. The molecule’s efficacy is maintained during one year of treatment in patients with narcolepsy or obstructive sleep apnea (OSA), and solriamfetol generally is safe and well tolerated, said the researchers.
A Reanalysis of Phase III Data
Solriamfetol is a selective dopamine and norepinephrine reuptake inhibitor that promoted wakefulness in patients with narcolepsy in a large phase III trial. Investigators presented the results of three new studies of solriamfetol during the meeting. In the first study, Yves Dauvilliers, MD, PhD, a neurologist at Gui-de-Chauliac Hospital in Montpellier, France, and colleagues reanalyzed the data from the phase III trial to assess the drug’s efficacy in subgroups of patients with and without cataplexy.
Eligible patients were adults with type 1 or type 2 narcolepsy, a baseline Maintenance of Wakefulness Test (MWT) result of less than 25 minutes, and an Epworth Sleepiness Scale (ESS) score of 10 or greater. Patients were randomized in equal groups to placebo or a 75-mg, 150-mg, or 300-mg dose of solriamfetol for 12 weeks. The primary end points were the change from baseline to week 12 in sleep latency on the MWT, the ESS, and the Patient Global Impression of Change (PGI-C) scale.
Of the 231 patients included in the analysis, 117 had cataplexy. The investigators observed no key baseline differences i
Among participants with cataplexy, the mean change in sleep latency at Week 12 was 1.8 minutes in the placebo group, 3.4 minutes in the 75-mg group, 7.9 minutes in the 150-mg group, and 10.7 minutes in the 300-mg group. Among participants without cataplexy, the mean change was 2.6 minutes in the placebo group, 6.0 minutes in the 75-mg group, 11.6 minutes in the 150-mg group, and 13.8 minutes in the 300-mg group.
The mean decrease in ESS score among patients with cataplexy at Week 12 was 1.8 points among controls, 3.1 points in the 75-mg group, 5.6 points in the 150-mg group, and 6.3 points in the 300-mg group. Among patients without cataplexy, the mean decrease was 1.5 points in controls, 4.5 points in the 75-mg group, 5.2 points in the 150-mg group, and 6.4 points in the 300-mg group.
A significantly greater percentage of patients in the 150-mg and 300-mg groups had improvement in PGI-C at Week 12, compared with controls, regardless of whether they had cataplexy. Among patients without cataplexy, a significantly greater percentage of those who received 75 mg of solriamfetol also had improvement in PGI-C at Week 12, compared with controls.
Solriamfetol Improves Work Productivity
Helene Emsellem, MD, Medical Director of the Center for Sleep and Wake Disorders in Chevy Chase, Maryland, and colleagues analyzed data from the same phase III study to examine solriamfetol’s effects on health-related quality of life and work productivity. These outcomes had been measured using the Functional Outcomes of Sleep Questionnaire, short version (FOSQ-10); the Work Productivity and Activity Impairment questionnaire for Specific Health Problem, which measures absenteeism, presenteeism (ie, working while impaired), and activity impairment outside of work; and the 36-Item Short Form Health Survey version 2 (the SF-36 v2), which includes physical and mental components. Dr. Emsellem and colleagues calculated the least-squares mean change in these measures from baseline to Week 12.
At baseline, mean FOSQ-10 total score was 12.2 among controls, 11.4 in the 75-mg group, 11.7 in the 150-mg group, and 11.4 in the 300-mg group. A normal value is approximately 18. At Week 12, FOSQ-10 score improved by 3.01 points in the 300-mg group, compared with 1.56 among controls. The difference between these groups was statistically significant. FOSQ-10 score improved by 2.39 in the 75-mg group and by 2.57 in the 150-mg group, but these results were not statistically significant.
At Week 12, the 150-mg and 300-mg doses of solriamfetol significantly reduced activity impairment outside of work, compared with placebo. In addition, the 150-mg dose significantly reduced presenteeism and a composite of absenteeism and presenteeism, compared with placebo. Solriamfetol had little effect on absenteeism, perhaps because absenteeism was uncommon at baseline, said Dr. Emsellem.
In addition, the 300-mg dose of solriamfetol significantly increased by 3.29 points the physical component summary score of the SF-36 v2, compared with placebo, which yielded a 1.06-point increase. The other doses did not significantly improve the physical component summary score. Solriamfetol did not significantly improve the mental component summary score.
Data Suggest Long-Term Efficacy
Pharmacologic treatment for narcolepsy often lasts for a long period of time, but the treatment periods in many clinical trials are comparatively short. Atul Malhotra, MD, Professor of Medicine at the University of California, San Diego, and colleagues conducted a study to examine the long-term safety and efficacy of solriamfetol.
Eligible participants had narcolepsy or OSA and had previously completed six- or 12-week trials of solriamfetol. Patients in Group A were enrolled into the long-term study immediately after having completed an earlier study, and patients in Group B were enrolled later after their completion of the earlier study.
Participants received open-label solriamfetol during a two-week titration phase. The subsequent maintenance phase lasted for 38 weeks for Group A and 50 weeks for Group B. After about six months of treatment, investigators randomized blinded patients to placebo or their assigned dose of solriamfetol for two weeks. After this randomized-withdrawal phase, all participants received solriamfetol.
The primary end point was the change in ESS score at the end of the randomized-withdrawal phase. Secondary end points were the changes in PGI-C and the Clinical Global Impression of Change (CGI-C) at the end of the randomized-withdrawal phase. The analysis was performed using a modified intention-to-treat population.
The investigators enrolled 643 participants into the study. Mean age was 49, 52% of the population was male, and mean BMI was 31.7. About 35% of participants had narcolepsy, and 65% had OSA. In all, 282 participants were assigned to the randomized-withdrawal phase, and 361 continued solriamfetol.
By the end of the randomized-withdrawal phase, ESS score had risen from 7.8 to 12.6 in the placebo group, compared with an increase from 7.3 to 8.5 in the solriamfetol group. The least-squares mean difference between the arms was –3.7.
About 65% of patients randomized to placebo reported worsening on PGI-C at the end of the randomized-withdrawal phase, compared with 28% of the solriamfetol group. Similarly, approximately 64% of patients randomized to placebo were rated as worse on the CGI-C at the end of the randomized-withdrawal phase, compared with 29% of the solriamfetol group.
At Week 40, Group A had sustained reductions in ESS score, which indicated long-term efficacy of solriamfetol. Group B had similar results during approximately one year of treatment. “There is no hint of tachyphylaxis,” said Dr. Malhotra. Improvements in PGI-C and CGI-C were stable over time.
No New Safety Concerns Emerge
The safety profile of solriamfetol in these studies was similar in participants with and without cataplexy and was consistent with that indicated by previous trials. The most common treatment-emergent adverse events in the phase III trial that Drs. Dauvilliers and Emsellem analyzed were headache, nausea, decreased appetite, nasopharyngitis, dry mouth, diarrhea, and anxiety. The rate of adverse events increased with increasing dose. More participants in the solriamfetol group discontinued the trial, compared with the placebo group. Solriamfetol did not affect BMI. Safety results were similar in Dr. Malhotra’s trial. Solriamfetol had “a durable effect without major side effects,” he said.
Jazz Pharmaceuticals, which is headquartered in Dublin, is developing solriamfetol and sponsored all three studies. The company filed a new drug application for solriamfetol with the FDA in March and expects a regulatory decision in late December.
—Erik Greb
Suggested Reading
Bogan RK, Feldman N, Emsellem HA, et al. Effect of oral JZP-110 (ADX-N05) treatment on wakefulness and sleepiness in adults with narcolepsy. Sleep Med. 2015;16(9):1102-1108.
Scrima L, Emsellem HA, Becker PM, et al. Identifying clinically important difference on the Epworth Sleepiness Scale: results from a narcolepsy clinical trial of JZP-110. Sleep Med. 2017;38:108-112.