Evotec Reports Details of the Positive Proof-of-Concept Phase II Study in Insomnia With EVT 201
Very Robust Findings on the Key Problems Faced by Insomniacs, i.e. Sleep Onset and Sleep Maintenance
Evotec to Host a Conference Call Today at 11:00 am CET (10:00 am UK time, 5:00 am EST, 7:00 pm AEST) Directly From the Worldsleep07 Congress in Australia
HAMBURG, Germany and OXFORD, England, September 05, 2007 /PRNewswire-FirstCall/ -- Evotec AG presented today at the worldsleep07 congress in Cairns, Australia the details of the results from its first Phase II clinical trial of EVT 201 in patients with primary insomnia. EVT 201 is a partial positive allosteric modulator (pPAM) of the GABAA receptor complex. The double-blind, placebo controlled cross-over study of two doses of EVT 201 (1.5mg and 2.5mg) in 67 completed patients was conducted in sleep labs in the US using objective polysomnography (PSG). After having published top-line results in a press release on 4 June 2007, the results of the detailed analysis are herewith reported.
The detailed analysis showed that all endpoints achieved an even higher level of statistical significance than first indicated. The pre-specified intention-to-treat analysis of the study showed that on both of the co-primary endpoints of Total Sleep Time (TST) and Wake After Sleep Onset (WASO) the statistical significance of both doses against placebo was p<0.0001.
Highly statistically and clinically meaningful effects were also found on both the Latency to Persistent Sleep (LPS) and TST in the second half of the night, indicating strong effects on both sleep onset and sleep maintenance. In addition to these objective PSG results, there were highly significant improvements, at both dose levels, on the subjective perception of sleep quality.
The following morning there was no subjective perception of any residual sedation. The Digit Symbol Substitution Test (DSST) showed a small but clinically insignificant change tested the next day 9 h after dosing.
The PSG analysis also showed that EVT 201 did not have a negative impact on sleep architecture unlike many benzodiazepine full agonists.
As in all previous clinical studies, EVT 201 was demonstrated to be safe and well-tolerated at both doses. No serious or unexpected adverse events were reported.
The table below shows the actual results for each of the primary and selected secondary endpoints:
Parameter Placebo EVT 201 EVT 201 N=67 1.5 mg 2.5 mg Adjusted mean WASO (mins) 47.2 (26%) 38.2 (40%) 63.9 p<0.0001 p<0.0001 Adjusted mean TST (mins) 412 (9%) 424 (12%) 379 p<0.0001 p<0.0001 Adjusted mean LPS (mins) 25.2 (40%) 21.6 (49%) 42.3 p<0.0001 p<0.0001 Adjusted mean Total Wake 32.1 (25%) 26.7 (38%) Time 2nd half (mins) 42.9 p=0.0008 p<0.0001 Adjusted mean Slow Wave 30.4 (2.4%) 29.9 (0.7%) Sleep (mins) 29.7 NS NS Subjective sleep quality 75.2% 78.7% (very good/good) 41.2 % p<0.0001 p<0.0001 Adjusted mean DSST 56.2 54.3 (number correct) 58.5 p= 0.0028 p<0.0001 Subjective residual sedation 57.6% 48.0% (very alert/somewhat alert in %) 52.6 % NS NS
The large effect size on Total Wake Time (TWT) for the second half of the night indicates that EVT 201 is highly effective in maintaining sleep throughout the night. This was further confirmed by the hour-by-hour analysis of TWT. Although the study was not powered for such an analysis, the reduction in TWT produced by EVT 201 was statistically significant for all hours of the night apart from hour 7 which came very close to reaching statistical significance (p= 0.058).
Commenting on the results, Dr John Kemp, Chief Research & Development Officer, Evotec AG, said: "I'm absolutely delighted with the results of this proof-of-concept Phase II study. The magnitude of effect on sleep maintenance appears more robust than those seen with other agents in similar cross-over design studies. In particular, we are not aware of similar studies that have demonstrated such statistically significant effects on Total Wake Time in the second half of the night and Total Wake Time each hour."
Jorn Aldag, President and Chief Executive Officer, Evotec AG, said: "Although certain aspects of insomnia are addressed by current treatments, there is no drug yet available which meets all the needs of insomnia patients. In our study EVT 201 demonstrated extremely robust findings on all key aspects of the problems faced by insomniacs, i.e. sleep onset and sleep maintenance and yet was without the patients feeling any drug hang-over effects after waking in the morning. We believe this gives EVT 201 a very competitive profile compared to the currently available insomnia treatments and to those in late stage clinical development."
Principal Investigator Dr James Walsh, Executive Director of the Sleep Medicine and Research Center, St John's Mercy Medical Center, Chesterfield, Missouri, US, said: "Due to its partial positive allosteric modulation of GABAA receptors, EVT 201 provides a novel approach to the treatment of insomnia, yet since the GABAA system is a well understood pathway, the risk of unexpected side effect findings are low compared to completely novel mechanisms. This together with robust effect sizes seen in this study, particularly with regard to sleep maintenance, offers considerable promise for the drug as a treatment for insomnia patients."
A second Phase II clinical trial of EVT 201 in elderly patients with primary insomnia for further differentiation is ongoing. Top-line results from this trial are expected to be announced in October 2007.
Webcast Presentation and Conference Call
Evotec will hold a conference call today at 11.00 am CET (10.00 am UK time/05.00 am EST, 07.00 pm AEST) to present details on positive Phase II study in insomnia with EVT 201. Dr John Kemp, Chief Research & Development Officer, and Dr Tim Tasker, Executive Vice President, Clinical Development will lead the call.
Australia: +61-2-8223-9234 Germany: +49-69-9897-2631 UK: +44-20-7138-0814 Switzerland: +41-44-800-9659 US: +1-718-354-1157 Webcast: http://www.evotec.com
The on-demand version of the webcast will be available on our website: http://www.evotec.com - Investors - Webcasts.
Contact: Evotec AG Anne Hennecke SVP, Investor Relations & Corporate Communications Phone: +49-(0)40-56081-286 Fax: +49-(0)40-56081-333 E-Mail:email@example.com
CONTACT: Contact: Evotec AG, Anne Hennecke, SVP, Investor Relations &Corporate Communications, Phone: +49-(0)40-56081-286, Fax:+49-(0)40-56081-333, E-Mail: firstname.lastname@example.org
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Posted: September 2007