Obecure Ltd (http://www.obecure.com)., a subsidiary of Bio-Light Israeli Life Science Investments Ltd. (TASE: BOLT), announced today the execution of a licensing and clinical supply agreement with Farmaceutici Formenti SPA, the Italian Subsidiary of the Grunenthal Group (Grunenthal). The agreement extends the 2008 strategic supply agreement between the parties to know-how and patents covering innovative extended release formulations of betahistine dihydrochloride, the active pharmaceutical ingredient of the company's proprietary drug Histalean(R). The extended release formulation (XR) allows the drug to achieve greater plasma concentrations for a longer duration and is thus likely to improve its beneficial actions.
Histalean(R) is comprised of betahistine dihydrochloride, a dual action histamine type H1 receptor agonist and a histamine type H3 negative autoreceptor inhibitor. It is a highly safe generic drug, approved since the 1960s for treatment of Meniere's disease (vertigo) in most countries. In the US, although its safety was not in doubt, the drug was withdrawn in 1972 for insufficient efficacy in this disease.
Obecure is focused on development of Histalean(R) 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(R) with olanzapine (Zyprexa(R)), 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(R)), quetiapine (Seroquel(R)) and aripiprazole (Abilify(R)). Interestingly, both side effects are mainly caused by the affinity of these drugs to histaminic H1 receptor and their inhibition of histaminergic neurotransmission.
Obecure's hypothesis is that Histalean(R)'s "prohistamine" activity counters SGA's side effects by offsetting their antihistamine action. Indeed, the current clinical trial results suggest that the dose required to effect mitigation of SGA-associated side effects (at least 144 mg/day) may exceed that which is approved for Menieur's disease (48 mg/day). As such high doses have been shown safe, alone and in conjunction with olanzapine, the company has an interest in pursuing the clinical evaluation of innovative high dose and extended release formulations, as developed by the Grunenthal Italian subsidiary. "This agreement is a major step forward in our effort to develop Histalean(R) and ensure its benefit to psychiatric patients treated with antipsychotic drugs" said Dr. Yaffa Beck, Chief Executive Officer of Obecure, adding that "It not only assures us a high quality drug manufacturer and supplier of extended release betahistine formulations for our clinical studies, it also enhances the probability of our clinical success, as well as our intellectual property portfolio."
Fulfilling a great and previously untapped market need, the improved tolerability and efficacy of the second generation antipsychotic drugs (SGA), was translated to annual sales growth from <$1 billion in 1994 to >$15 billion in 2009. However, in recent years there has been growing concern of regulators and practitioners about these drugs' induction of weight gain, reducing patients' compliance and exposing 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.
According to the terms of the agreement, Grunenthal will supply Obecure with the XR betahistine and matching placebo tablets for use in its upcoming clinical studies and pending successful clinical outcomes will exclusively manufacture XR-Histalean(R) and be entitled to license it for distribution and sale in Italy.