Arena announces P1 insomnia drug data
clinical trial that is testing a novel insomnia compound, which
could treat the 30 to 40 per cent of US adults, who complain about
some level of insomnia in the course of a year, and the 10 to 15
per cent of US adults who complain that their condition is severe
or chronic.
APD125 is an orally bioavailable, selective inverse agonist of the 5-HT2A serotonin receptor. Currently marketed drugs for insomnia generally 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.
By selectively targeting the 5-HT2A receptor, APD125 acts through a different mechanism than currently marketed insomnia drugs and blocks a general CNS activating effect. Because of the different mechanism of action, APD125 may not have the side effects generally associated with currently marketed drugs.
The Phase 1 program consisted of three clinical trials, APD125-001, APD125-002 and APD125-003, designed to evaluate the single and multiple dose safety and pharmacokinetics of APD125 in normal volunteers. Additionally, it evaluated the pharmacodynamics of nighttime dosing using polysomnography to assess effects on sleep patterns in normal volunteers.
Results demonstrated that in all three of the clinical trials, subjects demonstrated a robust and statistically significant increase in the amount of deep, or slow wave, sleep and a positive signal in other sleep maintenance parameters, which may distinguish APD125 from currently available sleep therapeutics. APD125 may have extended sleep onset latency in normal volunteers.
"As we plan our Phase 2 trial, we look forward to evaluating the potential benefits of APD125 in chronic insomnia patients," said William Shanahan, Arena's vice president and chief medical officer.
"We expect to start our Phase 2 APD125 trial by the end of the year," added Jack Lief, Arena's president and chief executive officer.
Insomnia is characterised by inadequate or poor sleep due to nonrefreshing sleep, frequent wakening with difficulty falling back to sleep, difficulty falling asleep or waking too early.
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.
Currently marketed therapies include Ambien(zolpidem), marketed by sanofi-aventis, which is the market leader across the seven major markets, with revenues of $1.7 billion (€1.4 billion) in 2003.
Zaleplon (Sonata), an off-patent compound, and various benzodiazepines, including Diazepam (Valium). These therapies generally work by activating the GABA-A receptor in the brain, and cause a general CNS-suppressive effect.
While these drugs are effective at initiating sleep, they have side effects including the risk of developing tolerance to the drug and the potential for causing a sensation of dullness and lethargy upon awakening, often referred to as the "hangover effect."
In addition, these drugs are DEA-scheduled controlled substances due to their potential for abuse. Despite these limitations, current medications for insomnia are expected to have worldwide sales in excess of $2 billion in 2005.
New formulations are reaching the market and these leading brand products face competition from generics and from the new GABA-A receptor agonists: Lunesta (Sepracor) to launched in late 2004, Indiplon (Pfizer/Neurocrine) and Gaboxadol (Lundbeck/Merck) in mid-2005 and early 2007, respectively.
