Arena Pharmaceuticals Says Insomnia Drug Positive in Mid-Stage Trial
SAN DIEGO, Sept. 25 -- Arena Pharmaceuticals, Inc. today announced positive preliminary results from its Phase 2 clinical trial of APD125 in patients with chronic insomnia. APD125 is an orally available drug candidate discovered by Arena that is being evaluated in insomnia patients who have difficulty maintaining sleep after initial sleep onset. When compared to placebo, patients treated with APD125 experienced statistically significant improvements in measurements of sleep maintenance, or the ability to maintain sleep during the night after falling asleep. The improvements in measurements of sleep maintenance were achieved without any limiting next day cognitive effects. The data from the APD125 Phase 2 study are consistent with Phase 1 data and support further development of APD125 for the treatment of insomnia patients who have difficulty maintaining sleep.
"APD125 clearly has robust sleep maintenance properties," according to Dr. Thomas Roth of Henry Ford Hospital, who interpreted the polysomnography data for the Phase 2 trial. "In the trial, APD125 consolidated sleep in ways that are not accomplished by any currently available drug."
The Phase 2 trial of APD125 was a randomized, double-blind, placebo- controlled study evaluating the safety and efficacy of nighttime dosing in patients with chronic insomnia. The trial evaluated standard measurements of sleep, such as wake after sleep onset (WASO), wake time during sleep (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 in about 25 clinical sites in the United States. The trial employed a cross-over design: 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 polysomnography values for nights one and two (N 1/2) and for nights six and seven (N 6/7), versus baseline values. Efficacy was also measured subjectively using patient-completed questionnaires each morning following polysomnography evaluations.
APD125 significantly improved several endpoints measuring improvements in sleep maintenance, including WASO and WTDS. WASO is the time spent awake from first sleep to the end of a standardly prescribed eight hour sleep period. WTDS is the cumulative time spent awake from first falling asleep and last sleep: if a patient completes his or her sleep prior to the end of the eight hour sleep period, this time spent awake in bed is not included. As such, WTDS only accounts for time awake during a patient's sleep period for that night.
WTDS decreased from baseline by 45.8 and 46.6 minutes, respectively in the 10 mg and 40 mg doses at N 1/2, and by 46.1 and 46.9 minutes, respectively, at N 6/7; these differences were statistically significant for both doses at N 1/2 (p<0.0001 compared to placebo decrease from baseline of 32.4 minutes) and N 6/7 (p=0.0009 for 10 mg, p=0.0004 for 40 mg compared to placebo decrease from baseline of 35.6 minutes). The decrease from baseline in WASO was 52.5 and 53.5 minutes, respectively, for the 10 mg and 40 mg doses at N 1/2 (p<0.0001 for both compared to placebo decrease from baseline of 37.8 minutes). Improvements from baseline in WASO of 51.7 and 48.0 minutes were observed at N 6/7 (p=0.0131 and p=0.1994 compared to placebo improvement from baseline of 44.0 minutes).
Significant improvements also were seen in other important measurements of sleep maintenance, including a decrease in the number of awakenings and arousals (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 on N 1/2 and +2.5, -4.8, and -6.7 on N 6/7 for placebo, 10 mg, and 40 mg, respectively. APD125 also significantly increased the time spent in deep (Stage 3 and 4) sleep and at the same time decreased the amount of time spent in light (Stage 1) sleep (p<0.0001 at 10 mg and 40 mg for both measures), providing further evidence for the sleep maintenance properties of APD125. Time in REM sleep was not meaningfully affected. As expected, based on the mechanism of APD125, no improvement in sleep onset was observed.
WTDS WASO (improvement in minutes (improvement in minutes from baseline) from baseline) Dose N 1/2 N 6/7 N 1/2 N 6/7 Placebo 32.4 35.6 37.8 44.0 10 mg 45.8 46.1 52.5 51.7 0.013 p value <0.0001 0.0009 <0.0001 1 40 mg 46.6 46.9 53.5 48.0 0.199 p value <0.0001 0.0004 <0.0001 4 Changes in Changes in # of Awakenings # of Arousals Dose N 1/2 N 6/7 N 1/2 N 6/7 Placebo 0.0 -0.9 +3.8 +2.5 10 mg -2.5 -2.3 -5.8 -4.8 p value <0.0001 <0.0001 <0.0001 <0.0001 40 mg -3.1 -2.5 -8.1 -6.7 p value <0.0001 <0.0001 <0.0001 <0.0001
While the study was not powered to demonstrate significance in the subjective endpoints, there were trends towards improvements in the quality of sleep, number of awakenings and total sleep time, with statistical significance for at least one time point and dose for each of these variables. The improvement was numerically greater for the 40 mg dose than the 10 mg dose for many of the objective and subjective measures.
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 cognitive function was observed.
"We are very encouraged by the results from the Phase 2 trial, which demonstrate improved sleep maintenance with an excellent tolerability profile," said Dr. William Shanahan, Arena's Chief Medical Officer. "We look forward to the continued development of APD125, and hope to bring a safe, efficacious and non-scheduled treatment to patients to help them maintain sleep and awake refreshed."
The data from the trial indicate that APD125 is efficacious for promoting sleep maintenance in patients with chronic insomnia. Based on the positive trial results, Arena plans to initiate a Phase 3 program in 2008. Arena is also considering an additional Phase 2 study that will evaluate the effects of APD125 on patients' subjective assessment of sleep.
Discovered by Arena, APD125 is a novel and orally available, highly selective inverse agonist of the 5-HT2A serotonin receptor. The vast majority of approved drugs for insomnia activate the GABA-A receptor in the brain, triggering a general CNS-suppressive effect. These drugs are DEA-scheduled, controlled substances due to their potential for abuse. Common side effects of GABA activating drugs include the risk of developing tolerance to the drug, impaired functioning when the drug is at therapeutic levels, and the potential for causing a sensation of dullness and lethargy upon awakening, often referred to as the "hangover effect."
By selectively targeting the 5-HT2A receptor, APD125 acts through a different mechanism than currently marketed insomnia drugs and inhibits one of several CNS activating pathways. Because of the different mechanism of action, APD125 may not have the side effects or abuse potential generally associated with currently marketed GABA-A drugs. 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). About 30 to 40 percent of U.S. adults complain about some level of insomnia in the course of a year, and about 10 to 15 percent of U.S. adults indicate that their condition is severe or chronic. In many cases, the lack of restful sleep impairs 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 product candidate, lorcaserin, is being investigated in a Phase 3 clinical trial program for the treatment of obesity. Arena's broad pipeline of novel compounds targeting G protein-coupled receptors, an important class of validated drug targets, includes compounds being evaluated independently and with its partners, 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.
Certain statements in this press release are forward-looking statements that involve a number of risks and uncertainties. Such forward-looking statements include statements about the results of the Phase 2 trial of APD125, continued development of APD125, the timing, number, protocol, design, scope and other aspects of APD125 trials, the tolerability, side effects, efficacy and the commercial and other potential of APD125, the possibility of APD125 to be a non-scheduled treatment, the relevance of indicators of sleep maintenance, and the breadth of Arena's pipeline, and about Arena's strategy, preclinical and internal and partnered clinical 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, Arena's planned clinical trials may not proceed at the time Arena expects or at all, the results of preclinical studies or clinical trials 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, and the timing and receipt of payments and fees, if any, from Arena's collaborators. 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.