The Food and Drug Administration (FDA) has approved Lybalvi (olanzapine and samidorphan) for the treatment of schizophrenia, as well as bipolar I disorder, as a maintenance monotherapy or for the acute treatment of manic or mixed episodes, as monotherapy or an adjunct to lithium or valproate.

Lybalvi is an atypical antipsychotic composed of samidorphan, a mu-opioid receptor antagonist, co-formulated with the established antipsychotic agent olanzapine, in a single bilayer tablet. The once-daily oral formulation is designed to provide the efficacy of olanzapine while mitigating olanzapine-associated weight gain.

The approval of Lybalvi was based on data from 27 clinical studies, including the phase 3 ENLIGHTEN-1 (ClinicalTrials.gov Identifier: NCT02634346) and ENLIGHTEN-2 (ClinicalTrials.gov Identifier: NCT02694328) studies for the treatment of adults with schizophrenia. 

In the ENLIGHTEN-1 study (N=403), the efficacy and safety of Lybalvi was evaluated in adults with acute exacerbation of schizophrenia. Patients were randomly assigned 1:1:1 to receive Lybalvi, olanzapine, or placebo once daily for 4 weeks. Findings showed that treatment with Lybalvi led to statistically significant reductions from baseline in Positive and Negative Syndrome Scale scores compared with placebo (primary endpoint; P<.001) in patients experiencing an acute exacerbation of schizophrenia; a similar improvement was noted in the olanzapine arm when compared with placebo (P=.004). The inclusion of samidorphan did not appear to negatively impact the antipsychotic efficacy of olanzapine.


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The ENLIGHTEN-2 (N=561) study compared the weight gain profile of Lybalvi to olanzapine in adults with schizophrenia. Patients were randomly assigned 1:1 to receive Lybalvi or olanzapine for 24 weeks. Results showed that treatment with Lybalvi was associated with statistically significant less weight gain compared with olanzapine (P=.003), and with a smaller proportion of patients who gained 10{d847ba2f23daf15c773bda6cb71ac33aa9166b9578a171d654c6e3c528a0b6bc} or more of their baseline body weight (P=.003).

The approval of Lybalvi for the treatment of bipolar I disorder was supported by the established efficacy and safety profile of orally administered olanzapine in adequate and well-controlled studies. 

As for safety, Lybalvi carries a Boxed Warning regarding an increased risk of mortality in elderly patients with dementia-related psychosis. The most common adverse reactions reported with Lybalvi for schizophrenia were increased weight, somnolence, dry mouth, and headache.

Lybalvi is supplied in 4 strengths of olanzapine/samidorphan: 5mg/10mg, 10mg/10mg, 15mg/10mg, and 20mg/10mg. The product is expected to be available in the fourth quarter of 2021.

References

  1. Alkermes announces FDA approval of Lybalvi™ for the treatment of schizophrenia and bipolar I disorder. [press release]. Dublin, Ireland: Alkermes plc; June 1, 2021. 
  2. Lybalvi [package insert]. Waltham, MA: Alkermes, Inc.; 2021.

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