>>Neurogen Proprietary Insomnia Compound Data for Two Studies Presented at Associated Professional Sleep Societies Annual Meeting
Wednesday June 13, 6:00 pm ET
BRANFORD, Conn.--(BUSINESS WIRE)--Neurogen Corporation (Nasdaq: NRGN - News) 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 in two sessions at the SLEEP 2007 Annual Meeting of the Associated Professional Sleep Societies (APSS) in Minneapolis, Minnesota. Two Phase 2b clinical studies with NG2-73 in chronic insomnia patients are currently being conducted by the Company. Data presented at the APSS meeting today includes the following:
"Effects of NG2-73 on Sleep Onset, Quality and Next Day Function in a Transient Insomnia Study" (Phase 2a)
NG2-73 is a partial agonist with preference for GABA(A) receptors containing the alpha-3 subunit. This mechanism of action may provide an important alternative to existing therapeutics for insomnia.
This double-blind, placebo-controlled, multi-center, randomized trial evaluated the efficacy of four dose groups of NG2-73 versus placebo in reducing Latency to Persistent Sleep (LPS) in healthy adults in a sleep laboratory, single-night, polysomnographic model of transient insomnia. This model of transient insomnia used both first night adaptation and "phase-advance" to create insomnia in healthy subjects. Subjects completed questionnaires assessing sleep effects, sleep quality, and next day functioning. Safety was monitored as per usual practice. Three hundred and sixty nine adults, aged 24 - 63, with no self-reported sleep disorders, were enrolled.
LPS was significantly reduced, compared to placebo, at all doses of NG2-73, in a dose-dependent manner with mean LPS of 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. Subjective sleep latency (sSL) was significantly reduced compared to placebo at all doses. All four NG2-73 treatment groups reported that their sleep had been significantly more refreshing than did the placebo group. At 1, 3, and 10mg, subjects felt alert and more than 87% of subjects considered their ability to concentrate as "very good" or "excellent" the morning following dosing, which was similar to the placebo group.
In this study, NG2-73 was generally well tolerated with adverse events (e.g. somnolence) attributable to the pharmacological action of the drug. There were no deaths, or drug-related serious adverse events or discontinuations, and no clinically important changes in safety laboratory reports, vital signs or electrocardiograms (ECGs).
In this study, NG2-73 was shown to be a potent sedative hypnotic which significantly reduced LPS at all doses tested, which was supported by subjective responses indicating rapid sSL. Most subjects expressed good concentration, alertness, and feeling refreshed the next morning. In this study, NG2-73 was also generally well-tolerated.
"Pharmacokinetic-Pharmacodynamic Effects of NG2-73, a Novel GABA(A) Agonist, and Zolpidem" (Phase 1)
NG2-73 is a GABA(A) receptor partial agonist which has preference for the alpha-3 subunit. In vivo animal experiments suggest that NG2-73 will have an improved side effect profile compared to zolpidem based on ethanol interaction and on assessments of learning and memory at equipotent hypnotic doses. The objectives of this study were to evaluate the relationship of dose, plasma concentration, and time to the pharmacokinetics (PK) and pharmacodynamics (PD) of NG2-73 at doses of 1, 3, 5, and 10 mg and zolpidem 10 mg versus placebo in healthy subjects.
This was a single-center, randomized, double-blind, placebo-controlled, six-way crossover study of single oral doses of NG2-73 administered to 19 healthy volunteers. Safety and tolerability were assessed, and kinetic-dynamic relationships were determined using plasma concentrations and multiple measures of PD including a visual analog scale of sedation (VAS), posturography (a method of quantifying balance), digit symbol substitution test (DSST), electroencephalogram beta frequency band (EBFB), and psychomotor vigilance testing (PVT).
In the primary analysis, NG2-73 had a statistically significant effect on sedation compared with placebo, and as measured by the Observer and the Subject VAS, there was a dose-response relationship. Similar effects were seen with the EBFB, DSST, PVT and posturography. Zolpidem 10 mg had effects that appeared similar to a dose between 3 mg and 5 mg of NG2-73. The duration of action of NG2-73 in the VAS ranged from approximately 1.5 hours for the 1 mg dose to approximately 6 hours with the 10mg dose. Zolpidem had a duration of action of approximately 6 hours. NG2-73 was well tolerated with no serious adverse events or withdrawals due to adverse events.
In this study, NG2-73 was shown to be a novel, potent, well tolerated, effective sedative hypnotic, with dose-dependent sedation lasting between 1.5 and 6 hours. There was consistency of effect across all PD measures.<<
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>>Neurogen Proprietary Insomnia Compound Data Presented at Associated Professional Sleep Societies Annual Meeting
Monday June 11, 6:00 pm ET
BRANFORD, Conn.--(BUSINESS WIRE)--Neurogen Corporation (Nasdaq: NRGN - News) today announced that data from previous Phase 1 clinical studies for NG2-73, the Company's lead compound for the treatment of insomnia, were presented today at the SLEEP 2007 Annual Meeting of the Associated Professional Sleep Societies (APSS) in Minneapolis, Minnesota. Two Phase 2b clinical studies with NG2-73 in chronic insomnia patients are currently being conducted by the Company. Data presented at the APSS meeting today includes the following:
"Safety and Tolerability in Early Phase I Studies of NG2-73, a Novel GABA(A) Sleep Agent"
NG2-73 is a GABA(A) receptor partial agonist which is alpha-3 subunit preferring. In vivo animal experiments suggest that NG2-73 will be a potent sedative hypnotic and may have an improved side effect profile compared to zolpidem, with respect to ethanol interaction and learning and memory at equipotent hypnotic doses.
The first-in-human studies included a single ascending dose and a five day multiple dose study in healthy subjects. The single ascending dose study started at 0.1 mg of NG2-73 and was planned to ascend to 100 mg of NG2-73 as a powder in a bottle formulation. The multiple ascending dose study was designed to test five days of once per day administration of 5, 10 and 20 mg tablets of NG2-73.
In the single ascending dose study, 48 subjects were enrolled (38 male and 10 female); all 48 subjects completed the study. Doses administered ranged from 0.1 to 60 mg. The 60 mg dose proved to be the maximum tolerated dose, as defined by the depth of sedation. The time to maximum concentration (Tmax) ranged from 0.33 to 3 hours and the half-life (T1/2) was 1.1 to 1.4 hours for all dosage groups. NG2-73 exhibited linear increases in maximum concentration (Cmax) and area under-the-curve (AUC, 0-inf) with increasing doses.
In the multiple ascending dose study, 32 subjects were enrolled (20 male and 12 female). Repeated daily dosing of NG2-73 did not result in accumulation and NG2-73 exhibited linear pharmacokinetics. The ability of NG2-73 to produce drowsiness and sleepiness was confirmed by the sedation assessment scores on the Stanford Sleepiness Scale and Visual Analog Scale in the multiple ascending dose study. In both studies the safety and tolerability of the compound were confirmed by the absence of serious adverse events, clinically significant laboratory findings, oxygen saturation level alterations, and electrocardiogram (ECG) abnormalities.
In these studies, NG2-73 was shown to be a novel sedative hypnotic which exhibited linear pharmacokinetics and was well tolerated up to 60 mg. This dosage is estimated to be 10- to 20-times the anticipated therapeutic dose.<<
The stock has sold off since this presentation of data, roughly 15% in a bit over a week. That last sentence suggests they will go with either the 3mg or 5mg dose, but more likely the 3mg dose, since the 5mg dose wasn't tested in the P2b trial. Docs can always prescribe two tablets to approximate the 5mg dose, yes? I don't see any real red flags here. The duration of sedation is perhaps too short for maintenance through the night? That's the only possible negative I can see. One can't push that metric without risking negative effects upon wakening. Was the Street somehow expecting better there?
I'm not really here for the insomnia program, anyhow. Crowded market, and Hypnion results looked stellar -- though they haven't presented LPS data that I have seen, rather WASO and total sleep time. But if NRGN goes much lower, I'll be buying back in. Gotta look at the burn. The psychological overhang of that shelf creates a sell the news environment for the stock.
Cheers, Tuck |
