|View printer-friendly version|
Auris Medical Announces Acquisition of Orphan Drug Designation and Secures Rights to In-License Additional Patents Related to Betahistine
- Acquires Orphan Drug Designation for betahistine for the treatment of obesity associated with Prader-Willi syndrome (PWS)
- Signs letter of intent to in-license two US patents covering use of betahistine for the treatment of depression and attention-deficit / hyperactivity disorder (ADHD)
"We are very excited to address additional neurological and metabolic disorders with our intranasal betahistine program," commented
In Prader-Willi syndrome, a rare genetic disorder characterized by progressive obesity, behavioral issues, delayed cognition and sleep disturbances, emerging research suggests positive effects of H3 histamine receptor inhibition on cognitive disability and excessive daytime sleepiness. Betahistine acts as an H3 receptor antagonist and uniquely, also as an agonist at the H1 histamine receptor, which plays a crucial role in the regulation of food intake. In animal studies, inhibition or knock-out of the H1 receptor resulted in increased appetite and the development of obesity, while food deprivation led to activation of H1 receptors in the hypothalamus.
Betahistine is expected to offer therapeutic benefits also in the treatment of ADHD and atypical depression. ADHD manifests with symptoms, such as hyperactivity, impulsivity and inattention and is estimated to affect in the US 8.8% of children between the ages of 4-17 years and 4.4% of the adult population. In a study with 16 adult ADHD patients, treatment with oral betahistine up to 200 mg resulted in a statistically significant improvement in surrogate markers for cognitive outcomes, attentional sensitivity in the Continuous Performance Task and inhibition in the Go/No-Go task, compared to placebo (p=0.02 and 0.004).
Atypical depression is a subtype of major depression. It is characterized by mood reactivity, fatigue, excessive somnolence, increased appetite or weight gain and cognitive deficits. Estimates in both community and clinical settings suggest that 15.7% to 36.6% of patients with depression present with atypical features. Data from two clinical trials with oral betahistine provide initial evidence for therapeutic benefits in depression.,
The two transactions are expected to close before year-end and to have no impact on the Company's development plans or financial position in the near-term. As previously announced, the Company prepares for the initiation of two proof-of-concept studies with intranasal betahistine in the first quarter of 2019 - one Phase 2 trial with AM-125 in vertigo and one Phase 1b trial with AM-201 in antipsychotic-induced weight gain. Based on the outcomes from these trials and discussions with health authorities about regulatory pathways, the Company plans to initiate specific developments in the new therapeutic indications as well.
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 6 to 29 times higher bioavailability.
This press release may contain statements that constitute "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Forward-looking statements are statements other than historical facts and may include statements that address future operating, financial or business performance or
 For a review see e.g. Lian et al. (2016), Ameliorating antipsychotic-induced weight gain by betahistine: Mechanisms and clinical implications, Pharmacol Res 106: 51-63.
 Visser et al. (2014), Trends in the parent-report of health care provider diagnosed and medicated attention-deficit/hyperactivity disorder:
 Kessler et al. (2006), The prevalence and correlates of adult ADHD in
 Moorthy et al. (2015), Safety, tolerability and pharmacokinetics of 2-pyridylacetic acid, a major metabolite of betahistine, in a phase 1 dose escalation study in subjects with ADHD. Biopharm. Drug Dispos. 36:429-439.
 For a review see e.g. Cristancho et al. (2011), Atypical depression in the 21st century: diagnostic and treatment issues. Psychiatric Times 28:42-47.
 Morozova et al. (2015), Effects and safety profile of betahistine in patients in the Russian contingent of OSVaLD, an open-label observational study in vestibular vertigo. Int J Gen Med. 8:47-53.
 Barak et al. (2016), A randomized, double-blind, placebo-controlled pilot study of betahistine to counteract olanzapine-associated weight gain. J Clin Psychopharmacol. 36(3):253-6.
Source: Auris Medical AG