SAN DIEGO, April 19 /PRNewswire-FirstCall/ —ACADIA Pharmaceuticals Inc.(Nasdaq: ACAD) today reported top-line results from a proof-of-conceptclinical study that assessed the effect of ACP-103 on deep, or slow wave,sleep in healthy older volunteers using polysomnography (PSG). Results of thestudy demonstrated that ACP-103 induced a robust and statistically significantincrease in slow wave sleep that was dose-related. ACP-103 treatment also hada positive impact on measures for sleep maintenance, including decreases inthe number of awakenings after sleep onset and in the time awake after sleeponset. ACP-103 is ACADIA's proprietary serotonin 5-HT2A inverse agonist thatblocks the activity of this key receptor.
"These data provide a proof-of-concept of the ability of ACP-103 toimprove the quality of sleep by increasing slow wave sleep," said UliHacksell, Ph.D., Chief Executive Officer of ACADIA. "This suggests thatACP-103 has potential as a novel treatment for sleep maintenance insomnia.ACADIA is currently in Phase II clinical development with ACP-103 for use inschizophrenia and treatment-induced dysfunctions in Parkinson's disease, twoindications with patients who frequently suffer from sleep disturbances. Thetrial results provide an excellent demonstration of the relationship betweendoses of ACP-103, plasma levels and effects of 5-HT2A-receptor antagonism onslow wave sleep, and, therefore, these data also will be helpful in the designof future ACP-103 clinical trials."
Clinical Trial Design
The clinical trial was a double-blind, placebo-controlled study involving45 healthy volunteers ranging in age from 40 to 64. The subjects wererandomized to one of five treatment arms, including placebo and four differentdoses (1 mg, 2.5 mg, 5 mg, and 20 mg) of ACP-103. Each group was administeredplacebo or the specified dose of ACP-103 once-daily each morning for 14consecutive days. All subjects underwent a two-night screening and baselinePSG evaluation. Additional PSG measurements were performed on the evening ofstudy days 1 and 13. The subjects also completed a Continuous PerformanceTest (CPT) to assess the potential impact on daytime functioning. Bloodsamples were collected at the beginning and end of the 14-day period todetermine ACP-103 levels in plasma. Of the 45 subjects, 20 of them alsounderwent a positron emission tomography (PET) study to measure 5-HT2A brainreceptor occupancy. The PET data are currently being analyzed.
Clinical Trial Results
The PSG data demonstrated that once-daily administration of 5 mg and 20 mgof ACP-103, the two highest doses used in this study, induced statisticallysignificant increases in slow wave sleep (p<0.001) as defined by the timespent in Stage 3 and Stage 4 sleep. These stages are commonly referred to asdeep, or slow wave, sleep. This robust effect was demonstrated both acutely(on study day 1) and after chronic administration (on study day 13). The twolower doses of ACP-103 were less effective than the two higher doses,demonstrating that the sleep effects of ACP-103 were dose-related.
Change in Slow Wave Sleep From Baseline in Minutes, Percentage, andStatistical Significance Between Each Dose and Placebo(n.s. = not significant)Day 1 Day 13Change From Baseline Change From BaselineN Minutes Percentage Minutes PercentageACP-103 (20 mg) 9 46.0 55% p<0.001 39.0 46% p<0.001ACP-103 (5 mg) 9 37.3 65% p<0.001 41.9 73% p<0.001ACP-103 (2.5 mg) 9 21.8 40% p<0.05 19.6 36% n.s.ACP-103 (1 mg) 9 6.4 10% n.s. 5.4 9% n.s.Placebo 9 -11.2 -17% n/a -3.1 -4.6% n/a
Results of the clinical trial also showed that treatment with ACP-103produced trends for improvement on measures for sleep maintenance, includingdecreases in the number of awakenings (p=0.04) and in time awake after sleeponset (p=0.09). Importantly, in contrast to most currently marketed insomniadrugs, which are sedative, sleep-inducing agents and have the potential toimpair daytime functioning, ACP-103 did not alter latency to sleep onset anddid not impair daytime functioning.
ACP-103 was safe and well tolerated in the study subjects and there wereno serious adverse events reported. All adverse events were mild to moderatein nature and were comparable across the placebo and ACP-103-treated groups.
About Sleep Maintenance Insomnia
Sleep maintenance insomnia (SMI) is the inability to stay asleep or toresume sleep after waking and is a major unmet medical need. Deep, or slowwave, sleep decreases with age, which leads to superficial sleep anddifficulty staying asleep. There is also an increased incidence of SMI inmedical, neurological and psychiatric conditions. Patients with SMI complainof frequent awakenings and difficulty staying asleep after falling asleep.Patients with these symptoms also frequently report impairments of daytimefunctioning. Most available sleep agents are sedatives that are ineffectivein treating the symptoms of SMI. The mechanism of action of ACP-103, as a5-HT2A inverse agonist, provides the opportunity to effectively treat thesymptoms of SMI without causing sedation.
About ACP-103
ACP-103 is a proprietary, potent and selective 5-HT2A receptor inverseagonist, which acts to block the activity of this key serotonin receptor.ACADIA has demonstrated that ACP-103 is safe and well tolerated in preclinicalstudies and in Phase I and initial Phase II clinical trials. ACADIA isdeveloping ACP-103 as a new therapy for treatment-induced dysfunctions inpatients with Parkinson's disease and as an adjunctive therapy forschizophrenia. ACADIA believes that ACP-103 may also have the potential totreat sleep maintenance insomnia.
About ACADIA Pharmaceuticals
ACADIA Pharmaceuticals is a biopharmaceutical company utilizing innovativetechnology to fuel drug discovery and clinical development of novel treatmentsfor central nervous system disorders. ACADIA currently has five PhaseII-stage clinical programs as well as a portfolio of preclinical and discoveryassets directed at large unmet medical needs, including schizophrenia,Parkinson's disease, sleep maintenance insomnia, and neuropathic pain. All ofthe drug candidates in ACADIA's product pipeline emanate from discoveries madeusing its proprietary drug discovery platform. ACADIA's corporateheadquarters is located in San Diego, California and it maintains research anddevelopment operations in both San Diego and Malmo, Sweden.
Forward-Looking Statements
Statements in this press release that are not strictly historical innature are forward-looking statements. These statements include, but are notlimited to, statements related to the potential for ACP-103 as a therapy forsleep maintenance insomnia and improving sleep quality and the utility of thetrial data for future trial design. These statements are only predictionsbased on current information and expectations and involve a number of risksand uncertainties. Actual events or results may differ materially from thoseprojected in any of such statements due to various factors, including therisks and uncertainties inherent in drug discovery, development, andcommercialization. In particular, results from Phase I, proof-of-concept, andPhase II clinical trials are not guarantees of results in any future trials orof ACADIA's ability to obtain regulatory approval for ACP-103. For adiscussion of these and other factors, please refer to ACADIA's annual reporton Form 10-K for the year ended December 31, 2005 filed with the United StatesSecurities and Exchange Commission as well as other subsequent filings withthe Securities and Exchange Commission. You are cautioned not to place unduereliance on these forward-looking statements, which speak only as of the datehereof. This caution is made under the safe harbor provisions of the PrivateSecurities Litigation Reform Act of 1995. All forward-looking statements arequalified in their entirety by this cautionary statement and ACADIA undertakesno obligation to revise or update this press release to reflect events orcircumstances after the date hereof.
Contacts:
ACADIA Pharmaceuticals Inc.
Lisa Barthelemy, Director, Investor Relations
Uli Hacksell, Ph.D., Chief Executive Officer
(858) 558-2871