Vanda Pharmaceuticals Inc. (Vanda) (NASDAQ: VNDA) presented additional data today at ENDO 2013, the Endocrine Society's 95th Annual Meeting, demonstrating that tasimelteon can entrain (synchronize) both melatonin and cortisol rhythms. This effect further confirms tasimelteon's potential to reset the master body clock and address the circadian desynchrony which is inherent in Non-24-Hour Disorder (Non-24). The SET (Safety and Efficacy of Tasimelteon) and RESET (Randomized-withdrawal study of the Efficacy and Safety of Tasimelteon to treat Non-24-Hour Disorder) Phase III studies were designed to assess the safety, efficacy and maintenance effect of tasimelteon for Non-24. Currently there is no approved FDA treatment for Non-24.
The simultaneous entrainment of both melatonin and cortisol reinforces tasimelteon as a circadian regulator, resetting the master body clock in the suprachiasmatic (SCN) nucleus. Cortisol is a key regulatory hormone which exhibits a strong circadian rhythm, usually rising in the early morning and falling in the evening. The circadian regulation of cortisol is necessary for the human body to be prepared for a wide range of daily activities and physiologic functions, including blood pressure variation, utilization of fatty acids, circulating lymphocytes and immunity.
"In addition to entrainment of melatonin, entrainment of cortisol establishes tasimelteon as a circadian regulator, addressing an unmet need for people living with Non-24, a debilitating circadian rhythm disorder," said Mihael H. Polymeropoulos M.D., Vanda's President and Chief Executive Officer.
In the SET study, tasimelteon achieved the primary endpoints of entrainment (synchronizing) of the melatonin (aMT6s) rhythm as compared to placebo and clinical response as measured by entrainment plus a score of greater than or equal to 3 on the Non-24 Clinical Response Scale (N24CRS). Tasimelteon also demonstrated significant improvement versus placebo across a number of sleep and wake parameters including measures of total sleep time, nap duration, and timing of sleep, as well as in the Clinical Global Impression of Change (CGI-C), an overall global functioning scale. In treated patients, daytime naps decreased by 46 minutes per day in the worst 25% of days in a cycle and nighttime sleep increased by 57 minutes per day during the worst 25% of nights in a cycle.
The RESET study demonstrated that continued treatment with 20mg of tasimelteon was required to maintain entrainment of melatonin and cortisol circadian rhythms in individuals with Non-24. Patients treated with tasimelteon maintained their clinical benefits while patients who received placebo showed significant deterioration in measures of nighttime sleep, daytime naps and timing of sleep. Furthermore, discontinuation of tasimelteon resulted in a rapid relapse to misaligned circadian rhythms, reinforcing the importance of chronic therapy.
"These results clearly demonstrate that tasimelteon can entrain the circadian clock and is able to align melatonin and cortisol rhythms to the 24-hour social day," said Steven W. Lockley, Ph.D., Associate Professor of Medicine, Division of Sleep Medicine, Brigham and Women's Hospital, Harvard Medical School.
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