Neurogen Proprietary Insomnia Compound Data Presented at American Psychiatric Association Annual MeetingBRANFORD, Conn.--(BUSINESS WIRE)--May 23, 2007 - Neurogen Corporation (Nasdaq: NRGN) today announced that data from previous Phase 1 and Phase 2a clinical studies for NG2-73, the Company's lead compound for the treatment of insomnia, were presented today at the American Psychiatric Association (APA) annual meeting in San Diego. Two Phase 2b clinical studies with NG2-73 in chronic insomnia patients are currently being conducted by the Company. Data presented at the APA meeting include the following abstracts:
--NG2-73, a Novel GABA(A) Partial Agonist, Rapidly Induced Sleep in a Transient Insomnia Study (Phase 2a)
NG2-73 is a partial GABA(A) agonist with preference for receptors containing the (alpha)3 subunit. Preclinical studies suggest that this compound has sedative hypnotic effects, supporting development as a potential treatment for insomnia.
This double-blind, placebo-controlled, randomized, multi-center study was designed to determine the effects of 1,3,10 and 20mg of NG2-73 compared to placebo on sleep onset as measured by Latency to Persistent Sleep (LPS) in healthy adults. The study design incorporated a single-night, polysomnography (PSG) model of transient insomnia using both first night sleep laboratory adaptation and "phase-advance" effects. Subjects were dosed in the sleep laboratory 2.5 hours prior to median habitual bedtime. "Lights off" and PSG recording started 30 minutes later. Safety was monitored by adverse event recording, physical exams, vital signs, electrocardiogram (ECG) and clinical laboratory tests. 369 healthy subjects aged 24-63 with no self-reported sleep disorders were enrolled.
LPS was statistically significantly reduced, compared to placebo, at all doses of NG2-73, and demonstrated a dose-response relationship. The mean times for LPS were 30.8 minutes for the Placebo group, and 17.8, 10.6, 7.8, and 6.6 minutes for the 1, 3, 10, and 20 mg NG2-73 groups, respectively. NG2-73 also had a statistically significant effect on Total Sleep Time and Sleep Efficiency at doses of 3mg and above. All doses had a statistically significant effect on "refreshing sleep," which was subjectively rated by study participants. NG2-73 was generally well tolerated, with adverse events (AEs) primarily reflecting an extension of the drug's sedative effects, including sedation, somnolence and dizziness. There were no drug-related, serious AEs or discontinuations, and no clinically important changes in safety labs, vital signs, or ECGs.
In this study, NG2-73 was shown to be a potent, well-tolerated, sedative hypnotic that significantly reduced time to onset of persistent sleep versus placebo at all doses tested.
--Exposure-Response Modeling of the GABA(A) receptor partial agonist NG2-73: An Approach for Determining Target Onset and Duration of Sleep Efficacy while Minimizing Next Morning Effects (Phase 1)
NG2-73, a GABA(A) partial agonist with preference for activation of (alpha)3 subunit receptors, represents a potential insomnia treatment with comparable efficacy and potentially fewer safety concerns relative to existing therapeutics. As with all therapeutics, determination of appropriate dose(s) and dosage formulation(s) is imperative to an efficient development program. To assist informed decision making, NG2-73 clinical development is being supported through intensive Exposure-Response (ER) modeling, in order to identify an optimal pharmacokinetic (PK) profile for sleep onset and maintenance while minimizing next morning effects.
Study 1, a Phase 1 crossover study where 19 subjects received single oral doses (1, 3, 5, 10 mg NG2-73, zolpidem 10 mg (Z10), and placebo), compared ER between NG2-73 doses and zolpidem. Plasma concentrations associated with half-maximal visual analog scale effects were approximately 13-fold greater for zolpidem vs. NG2-73. Maximal concentration (Cmax) for NG2-73 10 mg was approximately 6-fold less than Z10. Altogether, ER indicated an approximate 4-5 mg oral NG2-73 dose would provide similar maximal response relative to Z10, which supported Study 2 dose selection. From digit symbol substitution test (DSST) modeling, next morning NG2-73 concentrations of less than 2 ng/mL were targeted to minimize residual effects.
Study 2, a Phase 2a parallel group study (placebo, 1, 3, 10 and 20 mg NG2-73) in healthy adults (N=369, PK in 133 subjects), evaluated NG2-73 sleep onset (latency to persistent sleep, LPS) relative to placebo. NG2-73 Cmax related to half-maximal LPS decrease was less than Cmax observed from NG2-73 1 mg. DSST ER modeling consistently supported the less than 2 ng/mL target to minimize next morning effects.
ER models guided doses and formulations for ongoing Phase 2b patient studies, which aim to confirm these relationships in patients, and establish the concentrations necessary for sleep maintenance. Model-based development using ER will continue supporting informed NG2-73 clinical development decisions.
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.
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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.
Elaine Grimsell Dodge, 203-315-4615
Posted: May 2007