Jazz Pharmaceuticals Presents Long-Term Safety and Efficacy Data from Phase 3 TONES 5 Study of Solriamfetol for Excessive Sleepiness in Narcolepsy or Obstructive Sleep Apnea
"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," said
In the TONES 5 study, patients with ES due to narcolepsy or OSA, including those who had completed prior studies with solriamfetol, began treatment with solriamfetol in the two-week titration phase followed by a maintenance phase of up to 50 weeks. A subset of patients participated in a two-week placebo-controlled Randomized Withdrawal (RW) phase after approximately six months of treatment. The primary endpoint in the RW phase was change in Epworth Sleepiness Scale (ESS) from beginning to end of the RW. Secondary endpoints were Patient and Clinician Global Impression of Change (PGI-C and CGI-C, respectively).
In this trial, 643 patients (226 narcolepsy; 417 OSA) were administered solriamfetol and included in the safety population, and 458 completed the study. Two hundred and eighty-two patients were entered into the RW phase, and 280 completed this phase (141 receiving placebo and 139 receiving solriamfetol), representing the modified intent-to-treat population. At the end of the RW phase, patients who received solriamfetol remained improved, whereas those who were switched to placebo worsened. The Least Squares (LS) mean change in ESS score was 1.6 with solriamfetol compared with 5.3 with placebo, resulting in a LS mean difference of –3.7 (95% CI –4.80, –2.65; P<0.0001).
For both secondary endpoints (PGI-C and CGI-C), significantly greater percentages of patients who were switched to placebo were rated by their physicians and themselves as worse in their overall condition at the end of the RW compared with the solriamfetol group (both P<0.0001).
Long-term maintenance of efficacy was also demonstrated during the open-label period for up to one year by sustained reductions in mean ESS scores and improvements on the PGI-C and CGI-C scales.
The most frequent treatment-emergent serious adverse events (AEs; ≥5%) with solriamfetol were headache, nausea, insomnia, nasopharyngitis, dry mouth, and anxiety; 27 (4.2%) patients experienced one or more serious treatment-emergent adverse events. There was one death due to sepsis in a 70-year-old immunosuppressed male with OSA on solriamfetol 300 mg. The death was considered unrelated to study drug by the investigator.
About OSA and Excessive Sleepiness
OSA is a prevalent disease (as high as 14% in men and 5% in women) in which ES is a major presenting complaint in many cases.1-2 ES in OSA is associated with impairments in cognitive function, safety, productivity, interpersonal relationships, and overall quality of life. Positive Airway Pressure (PAP) therapy, with its most common form being Continuous Positive Airway Pressure (CPAP), has been shown to be an effective therapy for sleep-related airway obstruction, with frequent improvement in ES in many patients; however, not all patients tolerate CPAP therapy and among those who do, usage is highly variable. It is estimated that ES persists in 12%–65% of people utilizing CPAP for OSA.3-6
Narcolepsy is a debilitating neurological disorder characterized by ES, and the inability to regulate sleep-wake cycles normally.7 It affects an estimated one in 2,000 people in the United States, with symptoms typically appearing in early adulthood. It is estimated that more than 50% of patients with narcolepsy have not been diagnosed.8 Studies have shown it may take 10 years or more for people with narcolepsy to receive a correct diagnosis.9 ES is the primary symptom of narcolepsy and is present in all people with the disorder.2 ES is characterized by the inability to stay awake and alert during the day, resulting in unplanned lapses into sleep or drowsiness.2,7,10
Solriamfetol (JZP-110) is a selective dopamine and norepinephrine reuptake inhibitor (DNRI) in development for treatment of ES in adult patients with narcolepsy, OSA, and Parkinson's disease. In 2014, Jazz Pharmaceuticals acquired a license to develop and commercialize solriamfetol from Aerial Biopharma. Jazz Pharmaceuticals has worldwide development, manufacturing, and commercialization rights to solriamfetol, excluding certain jurisdictions in Asia. SK Biopharmaceuticals, the discoverer of the compound (also known as SKL-N05), maintains rights in 12 Asian markets, including Korea, China and Japan. Solriamfetol has orphan drug designation in the United States for narcolepsy.
- ES in adult patients with narcolepsy (TONES 2)
- ES in adult patients with OSA (TONES 3 and TONES 4), and
- The long term safety and maintenance of efficacy for the treatment of ES in patients with narcolepsy or OSA (TONES 5).
About Jazz Pharmaceuticals plc
"Safe Harbor" Statement under the Private Securities Litigation Reform Act of 1995
This press release contains forward-looking statements, including, but not limited to, statements related to solriamfetol as a potential treatment for ES in adult patients with narcolepsy or OSA and other statements that are not historical facts. These forward-looking statements are based on the company's current plans, objectives, estimates, expectations and intentions and inherently involve significant risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, risks and uncertainties associated with: the regulatory approval process, including the risk that the company is unable to obtain
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10. Ahmed I, Thorpy, M. Sleepiness: Causes, Consequences and Treatment, ed. Cambridge University Press. 2011:36-49.
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