BRANFORD, Conn.--(BUSINESS WIRE)--Neurogen Corporation (Nasdaq: NRGN - News) today announced positive top-line results from two dose-ranging, Phase 2b clinical trials in chronic insomnia patients with the Company’s proprietary insomnia agent, NG2-73, an alpha-3 preferring GABA(A) partial agonist. Multiple formulations were studied in each trial to determine the best profile for rapidity of sleep onset and maintenance of sleep through the night without residual sedation the next day.
The objective of the first trial--Study 202--was to measure efficacy in sleep maintenance, or the ability to maintain sleep throughout the night after falling asleep. In this study, NG2-73 achieved statistically significant results versus placebo (overall p less than 0.001) at all doses tested in the primary endpoint of sleep maintenance (measured by Wake After Sleep Onset - or WASO). Study 202 was the first study in which NG2-73 has been studied for sleep maintenance in chronic insomnia patients and confirms efficacy in this group. It included eight different controlled release doses of the compound.
The objective of the second trial - Study 203 - was to demonstrate efficacy in sleep onset, or the amount of time it takes to fall asleep, in chronic insomnia patients. In this study, NG2-73 achieved statistically significant results versus placebo (overall p less than 0.0001) at all doses tested in the primary endpoint of sleep onset (measured by Latency to Persistent Sleep - or LPS on the first two nights of treatment). Study 203 included two immediate release forms and three controlled release doses of NG2-73.
William H. Koster, PhD, President and CEO of Neurogen, said, “We are very pleased with the results of these studies. We wanted to answer two questions in these trials. First, can we achieve our target profile in chronic insomnia patients of rapid onset of sleep which is maintained throughout the night without next-day residual effects and, second, do we have a controlled release formulation of the drug that we believe we can take forward? The results of these studies indicate the answer to both questions is yes.
“From the sleep onset study it appears we have continued to demonstrate the rapid onset of action in insomnia patients which was observed in our previously reported transient insomnia study. We believe this has the potential to be an important differentiating feature of NG2-73. From the sleep maintenance study we have now established efficacy in chronic insomnia patients and, importantly, we observed five doses that achieved sleep maintenance but did not appear to cause next-day residual effects. Each of these doses used the same formulation technology which is the form we plan to take forward in future studies.”
Study 202: primary endpoint sleep maintenance
Study 202 was a randomized, double-blind, placebo-controlled, cross-over study conducted at five sites in the U.S. It was designed to determine the safety and efficacy of eight different dose and formulation profiles of NG2-73 compared to placebo. Total doses ranged from 3 mg to 12 mg. The primary endpoint was wake after sleep onset (WASO). In addition, sleep onset, as measured by latency to persistent sleep (LPS) and additional measures of sleep maintenance were explored in several secondary endpoints. The study was completed by 36 patients with chronic insomnia, aged up to 64 years. Each patient was randomly assigned to five treatment periods of study drug or placebo. The three nights of each treatment period were conducted in a sleep lab. The first two nights employed polysomnography to objectively measure various sleep parameters and PK testing occurred on the third night. Each WASO assessment was an average of two nights of sleep lab PSG measurements. PSG and PK data will be used to create exposure/response relationships in PK/PD models to determine optimum dose/formulations.
In top-line results of Study 202, NG2-73 demonstrated statistically significant improvement over placebo for reducing WASO at all dose and formulation profiles tested. Eight distinct dose and formulation profiles were tested in addition to placebo.
The following table shows mean WASO totals in minutes for each arm of the study:
Placebo 5mg 10mg 1mg IR+ “A” “A” 2mg “A” ---------------------------------------------------------------------- WASO (mean -minutes) 73.4 62.7 44.6 53.5 ---------------------------------------------------------------------- less less p value than than (compared to placebo) 0.033 0.001 0.001 ---------------------------------------------------------------------- 2mg IR+ 2mg IR+ 2mg IR+ 2mg IR+ 3mg IR+ 4mg “C” 5mg “A” 5mg “B” 10mg “B” 2mg “A” ---------------------------------------------------------------------- WASO (mean -minutes) 41.7 48.2 50.8 48.0 61.2 ---------------------------------------------------------------------- less less p value than than (compared to placebo) 0.001 0.001 0.017 0.001 0.020 ----------------------------------------------------------------------
IR--basic, or immediate release formulation of NG2-73 Different sustained formulations are designated as “A,” “B,” or “C”
Study 203: primary endpoint sleep onset
Study 203 was a randomized, double-blind, placebo-controlled, parallel group study conducted at 21 sites in the U.S. It was designed to determine the safety and efficacy of five different dose and formulation profiles of NG2-73 compared to placebo. Total doses ranged from 3 mg to 7 mg. The primary endpoint was the time it takes to fall asleep as defined by Latency to Persistent Sleep (LPS) on the first two nights of treatment. Sleep maintenance was also explored in several secondary endpoints. The study included 258 chronic insomnia patients, aged up to 64 years, who received study drug or placebo for approximately 14 days. The first two and last four nights of the study were performed in sleep labs and polysomnography was used to measure various sleep parameters. Each LPS assessment was an average of two nights of sleep lab PSG measurements. For the interim period of the study, patients self-medicated in their homes and kept sleep diaries. Approximately one-third of patients returned to the sleep lab for an additional night for PK testing. PSG and PK data will be used to create exposure/response relationships in PK/PD models to determine optimum dose/formulations.
In top-line results of Study 203, NG2-73 demonstrated statistically significant improvement over placebo for reducing LPS on the first two nights of treatment at all dose and formulation profiles tested. Five treatment arms were tested in addition to placebo.
The following table shows mean LPS difference from baseline in minutes: Placebo 3mg IR 7mg IR 1mg IR+ 3mg IR+ 2mg IR+ 2mg “A” 2mg “A” 5mg “B” ---------------------------------------------------------------------- LPS (mean -minutes difference from baseline) -23.2 -48.3 -56.4 -52.2 -47.2 -47.1 ---------------------------------------------------------------------- p value less (compared to placebo) than 0.0002 0.0001 0.0008 0.0016 0.0005 ---------------------------------------------------------------------- IR--basic, or immediate release formulation of NG2-73 Different sustained formulations are designated as “A” or “B”
Safety Profile
In both studies, NG2-73 was safe and well tolerated at all doses tested. One drug-related SAE was observed. The favorable safety and tolerability profile of NG2-73 observed in studies 202 and 203 was consistent with that observed in previous studies. NG2-73 has now been tested in more than 600 subjects.
Secondary Endpoints
Both studies included several secondary (exploratory) endpoints to obtain additional data on sleep onset, sleep maintenance and potential side-effects. These measures included LPS, WASO, Total Sleep Time (TST), Sleep Efficiency (SE), Wake Time During Sleep (WTDS), Digit Symbol Substitution Test (DSST) and Visual Analog Scales (VAS) on sedation. With regard to secondary endpoints, data from Study 202 - the sleep maintenance study -- were internally consistent and statistically significant with respect to sleep onset and maintenance. In this study, the controlled release formulation using matrix “A” described above generally performed best on all parameters with no next-day residual sedation effects. In study 203--the sleep onset study - sleep maintenance, as measured by the secondary endpoints described above, was not observed. In both studies, as expected, residual effects as measured by DSST, were observed in higher doses and with formulations with more prolonged release profiles.
Webcast
Neurogen will host a conference call and webcast to discuss this announcement at 8:30 ET today. The webcast will be available in the Investor Relations section of www.neurogen.com and will also be archived there. A replay of the call will be available after 1:00 pm ET today and accessible through the close of business, July 9, 2007. To replay the conference call, dial 888-286-8010, or for international callers, 617-801-6888, and use the pass code: 95330673.
About Neurogen’s Insomnia Program
Neurogen had announced results from Phase 2 testing in transient insomnia for NG2-73 in May 2006. The primary endpoint of that study measured the efficacy of NG2-73 in reducing time to onset of persistent sleep in a well established clinical model of transient insomnia in healthy adults. In the multi-center, 369 subject study, NG2-73 was shown to significantly reduce time to onset of persistent sleep versus placebo at all doses tested. NG2-73 was well-tolerated at all doses, with no drug-related serious adverse events or drug-related subject withdrawals.
To date, NG2-73 has been tested in Phase 1 and Phase 2 studies involving over 600 individuals and has been well tolerated at all doses tested.
Many prescription drugs approved for treatment of both onset and maintenance symptoms of insomnia work by modulating the gamma-aminobutyric acid (GABA) system of neurotransmitters. GABA is a chemical naturally released in certain parts of the brain in order to inhibit brain activity. Preclinical studies suggest that NG2-73 is pharmacologically distinct from currently marketed insomnia agents, as well as those in development, preferentially modulating alpha-3 receptor subtypes of the GABA-A neurotransmitter system. This preference for alpha-3 may result in sleep induction and maintenance without the side effect profile of currently marketed agents.
Helpful websites for information on insomnia:
National Sleep Foundation http://www.sleepfoundation.org
National Institutes of Health http://www.nih.gov
About Neurogen
Neurogen Corporation is a drug discovery and development company focusing on small molecule drugs to improve the lives of patients suffering from disorders with significant unmet medical need, including insomnia, obesity, pain, Parkinson’s disease, restless legs syndrome (RLS), and depression. Neurogen conducts its research and development independently and, when advantageous, collaborates with world-class pharmaceutical companies to access additional resources and expertise.
Neurogen Safe Harbor Statement
The information in this press release contains certain forward-looking statements, made pursuant to applicable securities laws, which involve risks and uncertainties as detailed from time to time in Neurogen’s SEC filings, including its most recent 10-K. Such forward-looking statements relate to activities, events or developments that Neurogen believes, expects or anticipates will occur in the future and include, but are not limited to, earnings estimates, statements that are not historical facts relating to Neurogen’s future financial performance, its growth and business expansion, its financing plans, the timing and occurrence of anticipated clinical trials, and potential collaborations or extensions of existing collaborations. These statements are based on certain assumptions made by Neurogen based on its experience and perception of historical trends, current conditions, expected future developments and other factors it believes are appropriate under the circumstances. Actual results may differ materially from those expressed or implied by such forward-looking statements as a result of various factors, including, but not limited to, risks associated with the inherent uncertainty of drug research and development, difficulties or delays in development, testing, regulatory approval, production and marketing of any of Neurogen’s drug candidates, adverse side effects or inadequate therapeutic efficacy or pharmacokinetic properties of Neurogen’s drug candidates or other properties of drug candidates which could make them unattractive for commercialization, advancement of competitive products, dependence on corporate partners, Neurogen’s ability to retain key employees, sufficiency of cash to fund Neurogen’s planned operations and patent, product liability and third party reimbursement risks associated with the pharmaceutical industry. Although Neurogen believes that its expectations are based on reasonable assumptions, it can give no assurance that the anticipated results will occur. For such statements, Neurogen claims the protection of applicable laws. Future results may also differ from previously reported results. For example, positive results or safety and tolerability in one clinical study provides no assurance that this will be true in future studies. Forward-looking statements represent the judgment of Neurogen’s management as of the date of this release and Neurogen disclaims any intent and does not assume any obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, unless required under applicable law.
Contact: Neurogen Corp. Elaine Grimsell Dodge, 203-315-4615 edodge@nrgn.com
Source: Neurogen Corporation
