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New Medicines

LybalviSchizophrenia and bipolar disorder in adults


New formulation

Development and Regulatory status

Phase III Clinical Trials
Oct 21Launched in the US [20].
Jun 21With concerns about its opioid antagonist effects, the US prescribing label will carry several warnings about use of opioids in patients taking Lybalvi [19]
Jun 21Approved in US [18]
Oct 20Alkermes announces positive vote outcomes from the joint meeting of the Psychopharmacologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee, appointed by FDA, on questions relating to ALKS 3831 for the treatment of adults with schizophrenia and for the treatment of adults with bipolar I disorder. The Prescription Drug User Fee Act (PDUFA) target action date for the ALKS 3831 NDA is Nov. 15, 2020 [17].
Aug 20FDA expected to review NDA in November 2020 [16].
Nov 19No plans to file for approval in the EU are described in the company 2018 annual report. Alkermes market numerous products in the UK through licensees; expect if ALKS 3831 is bought to the UK it will be through a collaboration with another company [14].
Nov 19Alkermes has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) seeking approval of ALKS 3831 (olanzapine/samidorphan) for the treatment of schizophrenia and for the treatment of bipolar I disorder [13].
Jul 19Alkermes announce plans to submit an NDA to FDA Q4 2019 for treatment of bipolar I disorder in addition to treatment of schizophrenia [12].
Nov 18Alkermes announced plans to submit an NDA to the FDA in mid-2019. However, the FDA´s advisory committees jointly voted 21 to 2 that the benefit-risk profile wasn’t adequate to support approval.[11]
Dec 17Alkermes plans to file in the US based on results from the ENLIGHTEN studies. [8].
Jan 15Alkermes has requested a meeting with the US FDA with a view to advancing ALKS 3831 into a pivotal development program in 2015 [1].


An oral, fixed-dose combination of olanzapine, an antagonist of dopamine-D1, dopamine-D2 and serotonin-2 receptors, and samidorphan, an opioid-mu receptor antagonist.
Incidence of schizophrenia is approximately 15.2 per 100,000 person-years and prevalence of approximately 7.2 per 1,000 persons. Most commonly starts in adolescence and early 20s, and in young people aged 10-18 schizophrenia accounts for 24.5% of all psychiatric admissions [2].
Schizophrenia and bipolar disorder in adults

Trial or other data

Mar 20PIII ENLIGHTEN-1 RCT (n=401) is published; it found combination of olanzapine and samidorphan resulted in statistically significant efficacy improvements over 4 weeks vs. placebo (PANSS total and CGI-S scores [least squares mean: −6.4; p<0.001 and −0.38; p =0.002, respectively) [15].
Mar 19PIII ENLIGHTEN-2 Study (NCT02694328) to evaluate weight gain of ALKS 3831 compared to olanzapine in adult subjects with schizophrenia starts recruitment. 540 patients will be recruited in the US, and is expected to complete collection of primary outcome data percent change from baseline in body weight at 24 weeks and proportion of subjects with >/= 10% weight gain in Feb 18 [5].
Jan 19Alkermes reports positive results from a 12-week, randomized, double-blind PII trial (n=300). ALKS 3831 achieved the primary efficacy endpoint, demonstrating equivalence to olanzapine in reduction from baseline in Positive and Negative Syndrome Scale (PANSS) total scores at Week 12 (mean difference 0.6 points; 95% CI: -1.2 – 2.5). ALKS 3831 also met the principal pre-specified secondary endpoint of the study, demonstrating a 37% lower mean weight gain compared to olanzapine at Week 12 in the full study population (p=0.006), and a 51% lower mean weight gain compared to olanzapine at Week 12 in a pre-specified subset of patients who gained weight in the one-week olanzapine lead-in (p<0.001). [3]
Nov 18Positive topline data announced from the PIII multicentre, double-blind, randomised, ENLIGHTEN-2 trial (n=561) of ALKS 3831 (olanzapine/samidorphan) for schizophrenia. The trial was designed to confirm ALKS 3831’s weight profile vs. olanzapine. After 6 months, fewer pts gained >10% of their baseline body weight vs. olanzapine (p=0.003). Weight gain curves for the two groups started to separate after the 4th week and continued to diverge. For pts receiving ALKS 3831, weight stabilised at Week 6.[11]
Oct 18PIII ENLIGHTEN-2 study (NCT02694328) has finished recruiting & expects to complete data collection in Nov 18 [10].
Sep 17PIII ENLIGHTEN-2 study (NCT02694328) is currently recruiting patients. Collection of primary outcome data now due to complete Aug 18 [9].
Jun 17Alkermes announces results from ENLIGHTEN-1. ALKS 3831 performed significantly better than placebo in reducing PANSS scores and physician impression ratings at week four. It also showed a numerically superior improvement compared to olanzapine although this wasn´t statistically significant. Alkermes notes this is the second study in which they observed this trend and they plan to continue to investigate this as they move beyond top-line data. Both ALKS 3831 and olanzapine groups gained weight in ENLIGHTEN-1, but that was likely to be a result of the higher level of care and nutrition that goes hand in hand with hospitalization for acute schizophrenia [7].
Jan 17NCT02634346 (ENLIGHTEN-1) is a PIII study of ALKS 3831 in 390 adult subjects with acute exacerbation of schizophrenia. The study started in Dec 15 and is due to complete Apr 18. It is enrolling subjects from the US, Bulgaria, Serbia and the Ukraine. NCT02669758 is a long-term follow up study [6].
Apr 15Positive topline results of ALKS 3831 in Schizophrenia from the complete 6-month PII trial. The randomised, dose-ranging PII study was designed in two stages: for the initial three months, pts were randomised to receive olanzapine or one of three doses of ALKS 3831 and antipsychotic efficacy and weight gain were assessed. For the second three months, all pts who received ALKS 3831 during the initial three months continued to receive ALKS 3831, and pts who had received olanzapine were switched to ALKS 3831. The reduction from baseline in PANSS total scores was equivalent to olanzapine during the initial three-month stage and this efficacy was maintained throughout the second three-month stage (change in PANSS total score from Week 12 to Week 24 was -1.7 points, 95% CI: (-2.7, -0.7). The beneficial effect on weight gain observed during the initial three months was also maintained during the second three-month stage. Mean percent change in body weight, from Week 12 to Week 24, was 0.5%, 95% CI: (-0.2%, 1.2%), indicating a consistent and durable blockade of olanzapine-induced weight gain [4].

Evidence based evaluations