Olanzapine/Samidorphan Maintains Mood Disorder Efficacy, Weight and Glycemic Tolerability at 4 Years

Combination olanzapine/samidorphan (LYBALVI) was associated with maintained long-term efficacy and consistent safety outcomes including managed weight gain and metabolic function in patients with mood disorders who were treated for ≥4 years, according to new findings.

In new phase 3 data presented at the American Psychiatric Association (APA) 2024 Annual Meeting in New York, NY, this weekend, a team of Alkermes-sponsored investigators reported that the fixed-dose, atypical antipsychotic-opioid antagonist combination drug was linked to efficacy and safety outcomes similar to short-term results in patients with either schizophrenia or bipolar I disorder (BD-I).

Investigators led by Rene S. Kahn, MD, PhD, system chair of psychiatry at Icahn School of Medicine of Mount Sinai conducted a long-term evaluation of the safety, tolerability, and durability of clinical effect associated with a 4-year regimen of olanzapine/samidorphan. They sought outcomes including characterization of weight gain and metabolic profiles over the duration of treatment.

“The…combination is approved for the treatment of patients with schizophrenia or BD-I and provides the established antipsychotic efficacy of olanzapine while mitigating olanzapine-associated weight gain,” the team noted.

Kahn and colleagues conducted a 48-month, multicenter, open-label extension assessment involving patients from 1 of 3 relevant completed phase 3 trials, including a pair of 52-week open-label studies assessing patients with schizophrenia, as well as a 12-week randomized controlled trial comparing the combination therapy to lone olanzapine in young adults with recent-onset schizophrenia or BD-1.

Investigators had patients continue their daily dose of 5 - 20 mg olanzapine plus 10 mg samidorphan for an additional 4 years; they adjusted patient doses as warranted during assessment. Long-term safety assessments included incidence of adverse events and change from baseline in body weight and waist circumference. Long-term efficacy endpoints included change in high-density lipoprotein (HDL), low-density lipoprotein (LDL) and total cholesterol triglycerides.

The team additionally sought long-term outcomes for glycemic control based on glucose and glycosylated hemoglobin levels, as well as antipsychotic efficacy per Clinical Global Impressions-Severity (CGI-S) scale.

The patient population included 524 enrolled participants, of whom 523 received ≥1 dose of olanzapine/samidorphan and 188 (35.9%) completed the full 4-year treatment period. Mean duration of exposure was 652 days. Mean patient age was 35.1 years old; they were predominately male (61.6%) and White (72.7%).

Adverse events occurred in 60% of all treated patients; the most common included weight gain (9.8%), headache (7.1%), anxiety (6.1%) and insomnia. Mean body weight change was just 1.47 kg following 4 years of olanzapine/samidorphan. Mean change in waist circumference was 0.61 cm from baseline to 4 years. Investigators additionally observed generally stable lipid and glycemic parameters during the treatment duration.

Disease symptoms remained stable in treated patients over the long period; mean change in CGI from baseline was 0.28 points per patient.

The team concluded their findings showed olanzapine/samidoprhan resulted in consistent safety outcomes per both body weight and lipid/glycemic outcomes during the 4-year open-label extension study.

“Similarly, olanzapine/samidorphan maintained symptom control during long-term treatment,” investigators wrote. “Based on these results olanzapine/samidoprhan maintained long-term antipsychotic efficacy while mitigating the weight gain and metabolic dysfunction associated with olanzapine.”

References

1. ^{Kahn R et al. Long-term Safety and Efficacy of Olanzapine/Samidorphan: Results of a 4-Year Open-Label Study. Paper presented at: American Psychiatric Association (APA) 2024 Annual Meeting. New York, NY. May 4-8, 2024.}
2. ^{Alicia J. FDA Approves Olanzapine and Samidorphan for Schizophrenia, Bipolar I Disorder. HCPLive. Published June 1, 2021. https://www.hcplive.com/view/fda-approves-olanzapine-samidorphan-schizophrenia-bipolar-disorder}