Obecure granted patent covering betahistine with olanzapine for mitigating antipsychotic drug associated weight gain

Feb 23 2010

Obecure Ltd., a subsidiary of Bio-Light Israeli Life Science Investments Ltd. (TASE:BOLT), has received notice of allowance from the US Patent Office for its two key patent applications covering methods of use and compositions covering the use of betahistine with olanzapine for the mitigation of the serious weight gain associated as a side effect of the antipsychotic drug.

“The commercial opportunity of adjunctive Histalean® therapy, to enable”

Obecure is focused on development of Histalean^® (high dose betahistine) as adjunctive to antipsychotic drug therapy for improved treatment of schizophrenia, bipolar disorder and major depression. Obecure has recently announced the outcomes of randomized, placebo controlled Phase 1b and pilot Phase 2 trials, showing that co-administration of Histalean^® with olanzapine (Zyprexa^®), safely and significantly reduced weight gain and somnolence, two of the most serious side effects associated with this drug, as with most of the second generation antipsychotics as a drug class, also including risperidone (Risperdal^®), quetiapine (Seroquel^®) and aripiprazole (Abilify^®).

These antipsychotic drugs are widely used to relieve symptoms of serious psychiatric diseases including schizophrenia, bipolar disease and major depression with cumulative prevalence >5% and early onset in adolescence and even childhood. However, in recent years there has been growing concern of regulators and practitioners about these drugs’ induction of weight gain. Recent publications suggest that olanzapine causes an average weight gain of about 8 kg in just 12 weeks. This not only reduces patients’ compliance, but also exposes them to metabolic syndrome, diabetes and cardiovascular disorders; a concern which has resulted in FDA’s issuance of black box warnings, and which has greatly affected prescription decisions. Moreover, daytime sleepiness (somnolence) induced by these drugs is seriously impacting patients quality of life – prohibiting driving, hampering their ability to hold jobs and/or continue with their education.

“The allowance of our leading US patents validate the novelty and practicality of our approach and are serving as the initial milestone in our evolving intellectual property” said Dr. Yaffa Beck, CEO of Obecure, adding that “Olanzapine is considered the most effective of the first line antipsychotic drugs, but is also known to cause substantial weight gain. It is thus the first drug we focused on.” The patent portfolio includes applications pending worldwide, covering methods and compositions of betahistine for management of weight and somnolence that are secondary side effects of most psychiatric drugs.

Histalean^® is comprised of betahistine dihydrochloride, a centrally active dual action “pro-histamine.” Betahistine is an agonist of type 1histamine receptors and an inverse agonist (inhibitor) of type 3 histamine receptor (the negative autoregulatory receptor of histamine), acting in concert to activate the histamine system, which downregulates feeding and enhances alertness and cognition. Based on the highly safe generic drug, approved since the 1960s in >100 million patients suffering from Ménière’s disease (vertigo) in most countries; it is unavailable in the US, where, although safety was not doubted, it was withdrawn by the FDA in 1972 for insufficient data of efficacy in Menieur’s.

The Company has recently extended its clinical supply agreement with Grunenthal-Italy to include higher dose extended release formulations of betahistine and is planning to initiate follow-on escalating dose clinical trials this year. "The commercial opportunity of adjunctive Histalean^® therapy, to enable "safer" antipsychotic treatment is clear, considering the annual turnover of $15 billion in this market,” says Dr. Ami Eyal, CEO of Bio-Light, the major investor in Obecure, adding that “we are currently seeking financial and pharmaceutical partners to assist us to achieve this challenge.”