ALKS-5461

Buprenorphine/samidorphan

Buprenorphine (top) + samidorphan (bottom)
Combination of
Buprenorphine	Opioid modulator
Samidorphan	Opioid antagonist
Clinical data
Routes of administration	Sublingual
Legal status
Legal status	US: Investigational New Drug
Identifiers
Synonyms	ALKS-5461

Buprenorphine/samidorphan (developmental code name ALKS-5461) is a combination drug formulation of buprenorphine and samidorphan acting as a κ-opioid receptor (KOR) antagonist which is under development by Alkermes as an adjunct to antidepressant therapy in treatment-resistant depression (TRD). It is also under investigation by Alkermes as a treatment for cocaine dependence, which is being funded by a grant from the National Institute on Drug Abuse (NIDA).

Clinical results with ALKS-5461 in Phase II have been described as "very encouraging", and researchers have stated that KOR antagonists including ALKS-5461 might work "extremely well for the treatment of major depression." However, data from two of three core Phase III trials was recently released and revealed that ALKS-5461 was safe and well-tolerated but, disappointingly, failed to meet its primary efficacy endpoints, although some efficacy was observed. The third and final core phase III study, FORWARD-5, has been completed, and it was announced on 20 October 2016 that ALKS-5461 met its primary efficacy endpoint in the study.

Following very positive phase II trial results, ALKS-5461 was granted Fast Track Designation by the Food and Drug Administration (FDA) for TRD in October 2013. During June and July 2014, three major phase III clinical trials were initiated in the United States to evaluate core efficacy for the use of ALKS-5461 as an adjunctive treatment for patients who have had an inadequate treatment response to antidepressant monotherapy with an agent such as a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI). Results of these trials are expected in 2016. In addition to these trials, nine smaller supplementary studies will also be conducted, and will together conclude phase III research. In January 2015, Alkermes announced positive results from FORWARD-1, the first completed phase III study.