- APD125 Significantly Improved Key PSG Parameters of Sleep Maintenance -
- Phase 2b Subjective Study Ongoing -
SAN DIEGO, June 12 /PRNewswire-FirstCall/ -- Arena Pharmaceuticals, Inc. (Nasdaq: ARNA) announced today that Dr. Thomas Roth of Henry Ford Hospital presented data from Arena's positive Phase 2a clinical trial of APD125 for the treatment of insomnia in an oral presentation at the SLEEP 2008 22nd Annual Meeting of the Associated Professional Sleep Societies in Baltimore, Maryland.
APD125 is an oral drug candidate discovered by Arena that is being evaluated for the treatment of insomnia in patients who have difficulty maintaining sleep after initial sleep onset. When compared to placebo in the Phase 2a clinical trial, patients treated with APD125 experienced statistically significant improvements in polysomnographic (PSG) measurements of sleep maintenance, or the ability to maintain sleep during the night after falling asleep. These improvements were achieved without any next day impairment of cognition or coordination.
"APD125 is a potential next generation treatment for improving sleep maintenance that could meet the needs of many patients looking to achieve better 'quality sleep'," stated Dr. Thomas Roth of Henry Ford Hospital, who interpreted the PSG data for the Phase 2a trial. "In the trial, APD125 clearly demonstrated robust sleep maintenance properties without any apparent pattern of side effects associated with the drug."
Arena is currently evaluating the effects of APD125 on patients' subjective assessment of sleep in a Phase 2b study.
APD125 Phase 2a Study Results
In a Phase 2a clinical trial, APD125 significantly improved several PSG endpoints measuring improvements in sleep maintenance, including wake after sleep onset (WASO) and wake time during sleep (WTDS). WASO, the primary endpoint, decreased from baseline by 52.5 minutes (10 mg) and 53.5 minutes (40 mg) at nights one and two (N 1/2) (p<0.0001 for both vs. placebo) and by 51.7 minutes (p=0.01) and 48.0 minutes (p=0.2) at nights six and seven (N 6/7), respectively. WTDS decreased from baseline by 45.8 minutes (10 mg) and 46.6 minutes (40 mg) at N 1/2 (p<0.0001 for both vs. placebo) and by 46.1 minutes (10 mg) and 46.9 minutes (40 mg) at N 6/7 (p<0.001 for both vs. placebo).
Importantly, the number of awakenings and number of arousals improved significantly for both doses and time points (p<0.0001 at both N 1/2 and N 6/7 at 10 mg and 40 mg for both variables). Changes in the number of awakenings were 0.0, -2.5 and -3.1 at N 1/2 and -0.9, -2.3 and -2.5 at N 6/7 for placebo, 10 mg and 40 mg, respectively. Changes in the number of arousals were +3.8, -5.8 and -8.1 at N 1/2 and +2.5, -4.8 and -6.7 at N 6/7 for placebo, 10 mg and 40 mg, respectively. The beneficial effect of APD125 was also evidenced by a significant reduction in wake time during the middle of the night (hours three through six). APD125 also significantly increased the time spent in deep (Stage 3 and 4) sleep while decreasing the amount of time spent in the lighter stages of sleep (Stages 1 and 2), providing further evidence for the sleep maintenance properties of APD125. Time in REM sleep was not meaningfully affected.
Treatment with APD125 was well tolerated, with no reports of serious adverse events and no emerging safety findings as compared to placebo. No next day impairment of cognition or coordination was observed and there was no evidence of treatment withdrawal symptoms.
APD125 Phase 2a Study Design
The Phase 2a trial of APD125 was a randomized, double-blind, placebo-controlled, three-way crossover study evaluating the safety and efficacy of nighttime dosing in patients with primary insomnia. The trial evaluated standard PSG measurements of sleep, such as WASO, WTDS, number of awakenings, number of arousals, total sleep time and latency to persistent sleep, and enrolled a total of 173 male and female patients, ages 18-64, in 24 sleep research centers in the United States. To qualify for enrollment, patients were required to have paired screening PSGs that demonstrated an average WASO greater than or equal to 60 minutes, with neither PSG less than 45 minutes.
Every patient received both active doses of APD125 (10 mg and 40 mg) and placebo in random order for one week, separated by a seven to nine day washout period between each dosing period. Efficacy was measured objectively by averaging PSG values for N 1/2 and for N 6/7, versus baseline values obtained by averaging results from the screening PSGs.
Discovered by Arena, APD125 is a novel and oral selective inverse agonist of the 5-HT2A serotonin receptor. The vast majority of approved drugs for insomnia work by activating the GABA-A receptor complex in the brain, causing a general suppressive effect on the central nervous system, or CNS. These GABAergic drugs are generally associated with CNS side effects, including a sensation of dullness and lethargy upon awakening, often referred to as the "hangover effect." Other potential problems associated with the GABAergic drugs include the risk of developing tolerance and drug dependency in at-risk populations. In addition, GABAergic drugs are scheduled controlled substances by the Drug Enforcement Administration due to their potential for abuse.
APD125 acts through a different mechanism than currently marketed insomnia drugs. Arena believes that by selectively targeting the 5-HT2A receptor, APD125 blocks one of several CNS activating pathways rather than initiating a general CNS suppressive effect. Because of the different mechanism of action, APD125 may not have the side effects or abuse potential generally associated with currently approved GABAergic drugs. Through its novel mechanism, APD125 has the potential to reduce insomnia symptoms by improving sleep maintenance.
Insomnia is characterized by inadequate or poor sleep due to nonrefreshing sleep, frequent wakening with difficulty falling back to sleep, difficulty falling asleep or waking too early. Most insomnia complaints relate to sleep maintenance issues, such as waking frequently or awakening too early, as opposed to problems with sleep latency (i.e. falling asleep). Between 30 to 40% of US adults report some level of insomnia and insomnia is a chronic problem for about 10% of the US adult population. The lack of restful sleep may impair the person's ability to carry out their daily responsibilities because they are too tired or have trouble concentrating.
Insomnia has a variety of causes. It is often a symptom of some other disease or condition (e.g. life stress, psychiatric and medical disorders, or use of certain medications), but it can also be a distinct disorder. The prevalence of insomnia increases with age and is more common in women. Common symptoms of acute insomnia are sleepiness, negative mood and impairment of performance. Chronic insomnia is often associated with fatigue, mood changes, difficulty concentrating and impaired daytime functioning.
About Arena Pharmaceuticals
Arena is a clinical-stage biopharmaceutical company focused on discovering, developing and commercializing oral drugs in four major therapeutic areas: cardiovascular, central nervous system, inflammatory and metabolic diseases. Arena's most advanced drug candidate, lorcaserin, is being investigated in a Phase 3 clinical trial program for the treatment of obesity. Arena's broad pipeline of novel compounds target G protein-coupled receptors, an important class of validated drug targets, and includes compounds being evaluated independently and with partners, including Merck & Co., Inc. and Ortho-McNeil Pharmaceutical, Inc.
Arena Pharmaceuticals(R) and Arena(R) are registered service marks of the company. "APD" is an abbreviation for Arena Pharmaceuticals Development.
Such forward-looking statements include statements about the results of
the Phase 2a clinical trial of APD125; the continued development and
evaluation of APD125; the protocol, design, scope and other aspects of
clinical trials of APD125; the tolerability, side effects, safety profile,
efficacy, mechanism of action and the commercial and other potential of
APD125 and other of Arena's drug candidates; the possibility of APD125 to
be a non-scheduled treatment; the relevance of indicators of sleep
maintenance; Arena's strategy, internal and partnered programs, and ability
to develop compounds and commercialize drugs. For such statements, Arena
claims the protection of the Private Securities Litigation Reform Act of
1995. Actual events or results may differ materially from Arena's
expectations. Factors that could cause actual results to differ materially
from the forward-looking statements include, but are not limited to,
clinical trials and studies may not proceed at the time or in the manner
Arena expects or at all, the results of clinical trials or preclinical
studies may not be predictive of future results, Arena's ability to partner
lorcaserin, APD125, APD791 or other of its compounds or programs, the
timing, success and cost of Arena's research, out-licensing endeavors and
clinical trials, Arena's ability to obtain additional financing, Arena's
ability to obtain and defend its patents, the timing and receipt of
payments and fees, if any, from Arena's collaborators, and Arena's ability
to redeem with common stock any outstanding shares of its series B
convertible preferred stock. Additional factors that could cause actual
results to differ materially from those stated or implied by Arena's
forward-looking statements are disclosed in Arena's filings with the
Securities and Exchange Commission. These forward-looking statements
represent Arena's judgment as of the time of this release. Arena disclaims
any intent or obligation to update these forward-looking statements, other
than as may be required under applicable law.
Contacts: Jack Lief Mary Claire Duch
President and CEO WeissComm Partners
David Walsey 212.301.7228
Director, Corporate Communications
Arena Pharmaceuticals, Inc.
858.453.7200, ext. 1682
|SOURCE Arena Pharmaceuticals, Inc.|
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