Hamilton, Bermuda, Oct. 11, 2019 (GLOBE NEWSWIRE) -- Auris Medical Holding Ltd. (EARS), a clinical-stage company dedicated to developing therapeutics that address important unmet medical needs in neurotology and central nervous system disorders, today announced positive interim results from its Phase 1b trial with AM-201 in antipsychotic-induced weight gain and somnolence. The study demonstrated good safety and tolerability of AM-201 over the four-week treatment period and revealed relevant reductions in olanzapine-induced weight gain and daytime sleepiness. In female study participants, who overall showed more pronounced changes than male participants, a reduction in weight gain of 1.1 kg against placebo was observed at the highest tested dose of 20 mg three times per day (probability of effectiveness = 90%). The study will now proceed to the next higher and final dose level of 30 mg to be tested on 30 healthy volunteers.
“We are very pleased to see the good safety and tolerability of intranasal betahistine confirmed over an extended period of time and are encouraged by the first efficacy signals observed in the indication of antipsychotic-induced weight gain and somnolence prevention“, commented Thomas Meyer, Auris Medical’s founder, Chairman and CEO. “We look forward to confirming and expanding these results in a larger dose cohort in the second leg of the study, for which we anticipate a data read-out towards the end of the first quarter of 2020.”
“Weight gain and somnolence are major side effects of olanzapine and other antipsychotic medications and often inflict a major burden on the health and quality of life of patients”, stated Nir Barak, MD, member of Auris Medical’s Scientific Advisory Board. “Olanzapine is still considered one of the most efficacious antipsychotic drugs, yet its clinical use is often restricted due to the risk of substantial weight gain and metabolic adverse effects such as impaired glucose tolerance, new onset diabetes, hyperlipidemia or cardiovascular disease. A major cause of the weight gain associated with the use of olanzapine and many other antipsychotic drugs is the inhibition of the histamine H1 receptor, which betahistine seeks to counteract.”
The Phase 1b trial with AM-201 in antipsychotic-induced weight gain and somnolence is being conducted at a single trial site in Europe and has enrolled 50 healthy volunteers to date. Participants received either AM-201 (1, 2.5, 5, 10 or 20 mg) or placebo three times a day in parallel with oral olanzapine (10 mg) once a day for four weeks. The primary efficacy outcome for the trial is the reduction in olanzapine-induced weight gain; the secondary efficacy outcome is the reduction in olanzapine-induced daytime sleepiness.
Betahistine is a small molecule structural analog of histamine, which acts as an agonist at the H1 and as an antagonist at the H3 histamine receptors. Unlike histamine, it crosses the blood-brain-barrier. It is known to enhance inner ear and cerebral blood flow, increase histamine turnover and enhance histamine release in the brain, increase release of acetylcholine, dopamine and norepinephrine in the brain and to result in general brain arousal. Betahistine for oral administration is approved in about 115 countries, with the US being a notable exception, for the treatment of vertigo and Meniere’s disease. The compound has a very good safety profile, yet it is also known that its clinical utility is held back by poor bioavailability. Intranasal administration of betahistine has been shown to result in 5 to 29 times higher bioavailability.
Intranasal betahistine is being developed under project code AM-201 for the prevention of antipsychotic-induced weight gain and somnolence. Many antipsychotic drugs are known to block the H1 histamine receptor, which is involved in the control of appetite and wakefulness, resulting in weight gain and somnolence as side effects. As an H1 receptor agonist, betahistine is thought to counteract the antipsychotics’ inhibitory effects; in addition, betahistine blocks presynaptic H3 histamine autoreceptors, thus increasing histamine release and in turn augmenting betahistine’s direct agonistic effects on H1 receptors.
About Auris Medical
Auris Medical is a biopharmaceutical company dedicated to developing therapeutics that address important unmet medical needs in neurotology and central nervous system disorders. The company is focused on the development of intranasal betahistine for the treatment of vertigo (AM-125) and for the treatment of antipsychotic-induced weight gain and somnolence (AM-201). These projects have gone through two Phase 1 trials and entered into proof-of-concept studies in 2019. In addition, Auris Medical has two Phase 3 programs under development: Sonsuvi® (AM-111) for acute inner ear hearing loss and Keyzilen® (AM-101) for acute inner ear tinnitus. The Company was founded in 2003 and is headquartered in Hamilton, Bermuda. The shares of Auris Medical Holding Ltd. trade on the NASDAQ Capital Market under the symbol “EARS.”
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Edison Advisors for Auris Medical