- Both co-primary endpoints, Wake After Sleep Onset and Total Sleep Time, and key secondary endpoints, including Latency to Persistent Sleep, were met at both doses - Evotec to host a conference call at 4pm CET (3pm UK time, 10am EST) today
HAMBURG, Germany | OXFORD, England, June 4, 2007-- Evotec AG (Frankfurt Stock Exchange: EVT) announced today positive top-line results from its first phase II clinical trial of EVT 201 in patients with chronic primary insomnia. EVT 201 is a partial positive allosteric modulator (pPAM) of the GABAA receptor complex. The double-blinded, placebo controlled cross-over study design of two doses of EVT 201 (1.5mg and 2.5mg) in 67 patients was conducted in sleep labs in the US using objective polysomnography. The pre-specified intention-to-treat analysis of the study showed statistically highly significant improvements between both doses of EVT 201 and placebo in both of the co-primary endpoints of Total Sleep Time (TST) (p<0.001) and Wake After Sleep Onset (WASO) (p<0.001). Notably, WASO during the second half of the night was also significantly (p<0.001) reduced, indicating that EVT 201 has efficacy in sleep maintenance throughout the night.
Improvements were also seen across pre-specified secondary endpoints. Latency to persistent sleep was markedly decreased by both doses of EVT 201 (p<0.001) and patients reported highly significant improvements in subjectively assessed quality of sleep (p<0.001 both doses). Treatment with EVT 201 was completely without effect on subjectively assessed residual sedation the next day and produced only a small decremental effect on the digital symbol substitution test (DSST) assessed at nine hours post dosing. Initial analysis showed that EVT 201 did not impair slow wave sleep unlike many benzodiazepine full agonists. The study therefore demonstrated EVT 201 has robust effects on both sleep onset and sleep maintenance and is without meaningful next day hang-over effects.
EVT 201 was demonstrated to be safe and well-tolerated at both doses without any serious adverse events.
Further analysis of the remaining secondary endpoints is ongoing.
Jörn Aldag, President and Chief Executive Officer, Evotec AG, said: "We are very pleased with the positive outcome of this clinical trial. Our first drug with proof-of-concept in patients is a major milestone in Evotec's transition into a CNS focused biopharmaceutical company."
Commenting on the results, Dr John Kemp, Chief Research & Development Officer, Evotec AG, added: "We have always considered that EVT 201 has the potential to help patients to fall asleep quickly, help them stay asleep during the night and allow them to awake in the morning feeling refreshed and without any hang-over effect. It thereby meets the major needs of insomniac patients without the need for a sustained release formulation. These results confirm that potential in the primary patient population."
Dr Tim Tasker, Executive Vice President Clinical Development, Evotec AG, added: "The results provide our first evidence that this partial agonist is effective in patients. The profile shows large effects on sleep onset and maintenance without any subjective evidence of hang-over the next day."
Principal Investigator Dr James Walsh, Executive Director of the Sleep Medicine and Research Center, St John's Mercy Medical Center, Chesterfield, Missouri, US, said: "This first study of EVT 201 in patients provided highly significant and robust effects upon polysomnographically measured sleep for both doses. In addition patients reported an improved quality of sleep. Ratings of alertness in the morning were not impaired and findings on DSST were quite small. These are encouraging results which offer significant promise for the drug as a treatment for insomnia patients."
A second Phase II clinical trial of EVT 201 in elderly patients with ch ronic insomnia for further differentiation is ongoing. Top-line results from this trial are expected to be announced by Q4 2007 / Q1 2008.
Study design This US, multi-centre, double-blind trial was designed to evaluate the efficacy of EVT 201 in a three way cross-over design in 67 patients with primary insomnia. Patients were screened for entry into the study and the eligibility criteria included: a diagnosis of primary insomnia according to DSM (Diagnostic and Statistical Manual of Mental Disorders) IV; mean LPS > 20 minutes, mean WASO ³ 40 minutes, mean TST 240-420 minutes, all determined during two consecutive nights PSG evaluation. Patients received two dose levels of EVT 201 and placebo, in a random order, for two consecutive nights with a 5-12 day washout between each period. The primary endpoints of this trial were to assess Wake After Sleep Onset (WASO) as well as Total Sleep Time (TST) determined by polysomnography (PSG). The secondary endpoints included additional PSG-based measures such as latency to persistent sleep, number of awakenings and effects on sleep architecture. In addition, patients evaluated sleep quality and quantity. Residual sedation was assessed by the Digit Symbol Substitution Test (DSST) and a categorical patient rating. Safety measures included adverse events and laboratory data.
Conference call Evotec will hold a conference call today at 4.00 pm CET (3.00 pm GMT/10.00 am US time East Coast) to discuss the top-line results.
Conference call numbers (listen only): Europe: +49.(0)69.5007 1309 (Germany) +44.(0)20.7806 1955 (UK) US: +1.718.354 1388 Webcast: www.evotec.com
The presentation slides are available via the webcast.
A replay of the conference call will be available for 24 hours and can be accessed in Europe by dialing +49.(0)69.22222 0418 (Germany) or +44.(0)20.7806 1970 (UK) and in the US by +1.718.354 1112. The access code is 1624428#. The on-demand version of the webcast will be available on our website: www.evotec.com - Investors - Webcasts.
Contact: Anne Hennecke, SVP, Investor Relations & Corporate Communications, Evotec AG, Phone: +49-40-56081-286, firstname.lastname@example.org