ALKS 3831 mitigates weight gain in phase 3 schizophrenia study

René Kahn

Patients with schizophrenia treated with ALKS 3831, a combination of olanzapine and samidorphan, had less weight gain than those treated with olanzapine alone, according to a presentation from the 2019 Congress of the Schizophrenia International Research Society.

“It was important to conduct this research because there is a need for new treatment options for patients with schizophrenia,” presenting author René Kahn, MD, PhD, the Esther and Joseph Klingenstein Professor and System Chair of Psychiatry at the Icahn School of Medicine at Mount Sinai, told Healio Psychiatry. “What is unique about ALKS 3831 is that it combines the efficacy of olanzapine, which is one of the most effective antipsychotics, with a much safer drug profile in that it does not induce the weight gain associated with olanzapine.”

In this randomized study, known as ENLIGHTEN-2, researchers examined weight gain with olanzapine/samidorphan compared with olanzapine alone for 24 weeks.

Adults with schizophrenia were randomized to receive once-daily matching olanzapine/samidorphan (10 mg/10 mg) or olanzapine (10 mg) oral tablets. The researchers titrated doses up to olanzapine/samidorphan 20 mg/10 mg or olanzapine 20 mg after the first week — but could be decreased back to initial dose depending on patient’s tolerability — and fixed doses for the study duration after the fourth week.

Kahn and colleagues examined percent change from baseline in body weight and proportion of patients with 10% or more weight gain at week 24 (primary endpoints) as well as the proportion of patients with 7% or more weight gain at week 24 (secondary endpoint). They also measured antipsychotic efficacy via the Positive and Negative Syndrome Scale (PANSS) and conducted safety assessments.

Of 561 patients (n = 280 in olanzapine/samidorphan group; n = 281 in olanzapine group), 352 completed treatment. At baseline, average weight was 77 kg in the olanzapine/samidorphan group compared with 77.45 kg in the olanzapine group.

At week 24, mean percent change in body weight was less in the olanzapine/samidorphan group than in the olanzapine group (4.21% vs, 6.59%; P = .003). Fewer patients in the olanzapine/samidorphan group than in the olanzapine group had a 10% or greater weight gain (17.8% vs. 29.8%; OR = 0.5; 95% CI, 0.31-0.8) as well as a 7% or greater weight gain (27.5% vs. 42.7%; OR = 0.5; 95% CI, 0.33-0.76). Both groups had similar improvements in PANSS total score at week 24.

Overall, 10.9% of patients discontinued due to adverse events. Common adverse events included weight gain (24.8% vs. 36.2% in the olanzapine/samidorphan vs. the olanzapine group), somnolence (21.2% vs. 18.1%), dry mouth (12.8%, vs. 8%) and appetite increase (10.9% vs. 12.3%).

“Olanzapine is considered one of the most effective antipsychotics for the treatment of schizophrenia, but its clinical utility is limited by its association with weight gain,” Khan said. “These findings show that we now have the potential to reintroduce olanzapine without the long-term weight gain and the negative health effects associated with its use.”

In addition, findings from a phase 3 schizophrenia study presented at the meeting by Sergey Yagoda, MD, PhD, from Alkermes Inc., evaluating the long-term safety, tolerability and efficacy of ALKS 3831 showed that the investigational agent was generally well-tolerated. Over the course of the 52-week study, patients experienced significant improvement in schizophrenia symptoms. – by Savannah Demko

References:

Kahn R, et al. A combination of olanzapine and samidorphan mitigates the weight gain observed with olanzapine alone: Results from the phase 3 ENLIGHTEN-2 schizophrenia study.

Yagoda S, et al. A phase 3, multicenter study to assess the long-term safety, tolerability and efficacy of ALKS 3831 in subjects with schizophrenia. Presented at: The 2019 Congress of the Schizophrenia International Research Society; Apr. 10-14, 2019; Orlando, Fla.

Disclosures: Kahn reports consulting for, grants and/or speaker fees from Alkermes, Janssen, Lundbeck, Merck, Minerva Neuroscience, Otsuka, Roche and Teva. Yagoda is an employee of Alkermes.