New long-term data demonstrates that the combination of olanzapine and samidorphan (OLZ/SAM), marketed as Lybalvi by Alkermes, maintains symptom control over four years in individuals with schizophrenia, schizophreniform disorder, or bipolar I disorder. This finding reinforces the potential of OLZ/SAM as a durable treatment option for these conditions.
The data comes from a phase 3, multicenter, open-label, long-term extension study conducted between June 2017 and September 2023. Patients who completed the ENLIGHTEN clinical program received an additional two to four years of treatment with OLZ/SAM. The study enrolled 524 patients, with 88% diagnosed with schizophrenia, 3% with schizophreniform disorder, and 9% with bipolar I disorder.
Sustained Symptom Control
The study assessed the durability of OLZ/SAM using the change from baseline in the Clinical Global Impression–Severity (CGI-S) scale and the time to study discontinuation. A negative score on the CGI-S indicates clinical symptom management. At two years, the mean change from baseline CGI-S score was -0.18, and at four years, it was -0.24. The median time to study discontinuation was 588 days, indicating sustained symptom control over the long term.
Safety and Tolerability
Regarding safety, 60% of participants reported an adverse event (AE) during the treatment period, with most AEs being mild or moderate. The most common AEs included weight gain (9.8%), headache (7.1%), anxiety (6.1%), insomnia (5.9%), somnolence (5.9%), nausea (5.7%), and decreased weight (5.7%). A total of 44 patients (8.4%) discontinued the study due to an AE.
Addressing Weight Gain Concerns
Antipsychotic medications are a cornerstone of treatment for schizophrenia and related disorders, reducing acute symptoms and the risk of relapse and hospitalization. However, weight gain and metabolic changes are frequent concerns associated with these medications, particularly olanzapine monotherapy. Studies have shown that olanzapine alone can lead to adverse cardiometabolic effects such as type 2 diabetes, dyslipidemia, and metabolic syndrome.
The addition of samidorphan to olanzapine aims to mitigate these weight gain issues while maintaining antipsychotic efficacy. The ENLIGHTEN-2 trial, for example, demonstrated a lower mean percent weight gain from baseline at 6 months compared to olanzapine alone, as well as a lower proportion of patients who gained 10% or more of their baseline body weight.
Clinical Implications
These long-term data support the use of OLZ/SAM for patients with schizophrenia, schizophreniform disorder, or bipolar I disorder. The combination offers a valuable option in the treatment landscape by providing sustained symptom control and addressing the critical issue of weight gain associated with olanzapine monotherapy. The study reinforces the role of OLZ/SAM in managing these complex psychiatric conditions effectively.
