A New Drug Application (NDA) has been submitted to the Food and Drug Administration (FDA) for olanzapine/samidorphan (ALKS 3831; Alkermes) for the treatment of schizophrenia, in addition to treatment of manic or mixed episodes associated with bipolar I disorder, as a monotherapy or adjunct to lithium or valproate, and for maintenance treatment of bipolar I disorder. 

The investigational product consists of the atypical antipsychotic, olanzapine, and a mu-opioid receptor antagonist, samidorphan, which is expected to mitigate weight gain associated with olanzapine. The application includes data from the ENLIGHTEN-1 and ENLIGHTEN-2 studies, in which treatment with the combination therapy was compared with placebo or olanzapine monotherapy in patients with schizophrenia. 

In ENLIGHTEN-1 (N=403), treatment with olanzapine/samidorphan resulted in statistically significant reductions from baseline in Positive and Negative Syndrome Scale (PANSS) scores compared with placebo (P<.001) in patients experiencing an acute exacerbation of schizophrenia; a similar improvement was noted in the olanzapine arm when compared with placebo. 

Results from ENLIGHTEN-2 (N=561), which was designed to confirm the favorable weight profile of olanzapine/samidorphan compared with olanzapine, demonstrated  both a lower mean percent weight gain from baseline at 6 months with the combination therapy compared with olanzapine (P =.003) and a lower proportion of patients who gained 10% or more of their baseline body weight at 6 months compared with olanzapine (P =.003).

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In addition, data from a 52-week, open-label, extension study showed that treatment with olanzapine/samidorphan resulted in durable antipsychotic effects with minimal weight gain (mean increase of 1.86kg from baseline).

As olanzapine is currently approved for the treatment of bipolar I disorder, the Company also included pharmacokinetic bridging data in the NDA to support treatment with olanzapine/samidorphan for this indication. 

Alkermes is seeking approval of 4 fixed-dose strengths of olanzapine/samidorphan: 5mg/10mg, 10mg/10mg, 15mg/10mg and 20mg/10mg. 

For more information visit alkermes.com.