) today announced the initiation of a phase 1/2 study of ALKS 5461 for treatment-resistant depression (TRD). ALKS 5461 is the combination of ALKS 33, a proprietary opioid modulator, and buprenorphine. TRD, which is also known as refractory depression, refers to depressive episodes that are not adequately controlled by standard antidepressant therapy. The multicenter, randomized, double-blind, placebo-controlled trial is designed to assess the safety and potential efficacy of ALKS 5461 in subjects with TRD. Alkermes expects to provide topline results from this study in the second half of calendar 2011.
"Many patients with depression do not adequately respond to existing pharmacological therapies, underscoring the unmet need for this serious and chronic disease," stated Elliot Ehrich, Chief Medical Officer of Alkermes. "The combination of ALKS 33 with buprenorphine to create ALKS 5461 leverages our expertise with opioid modulators and may create a non-addictive therapy for treatment-resistant depression."
The phase 1/2, multicenter, randomized, double-blind, placebo-controlled, parallel-group, multi-dose study is designed to evaluate the safety and tolerability of ALKS 5461 in 32 patients with major depressive disorder who had shown an inadequate response to previous antidepressant therapy. Two different ratios of the components will be given in an escalating dose titration once daily for seven days via sublingual administration. The pharmacokinetics and efficacy of ALKS 5461 will also be evaluated.
ALKS 5461 is designed to be a non-addictive, kappa antagonist for the treatment of TRD. Preclinical research has demonstrated that kappa blockade has antidepressant effects in behavioral models of depression. Both components of ALKS 5461 have established activity at mu opioid receptors, with ALKS 33 functioning as an antagonist of the mu receptor and buprenorphine as a partial agonist. The net effect of this combination may attenuate buprenorphine’s mu agonist effects, therefore making it potentially non-addictive.
About ALKS 5461
ALKS 5461 is the combination of ALKS 33 and buprenorphine. ALKS 33 is an oral opioid modulator that builds on Alkermes' scientific expertise in opioid biology and pharmacology, as well as the company’s clinical and commercial knowledge in the field of addiction and central nervous system disorders. Clinical studies of ALKS 33 in over 400 patients to date have shown that it is generally well tolerated with a duration of action consistent with once-daily dosing. ALKS 5461 is also in clinical development for the treatment of cocaine addiction, which is being funded through a grant from the National Institute on Drug Abuse (NIDA).