An investigational schizophrenia treatment demonstrated a superior weight gain profile, compared with olanzapine, in a phase 3 trial, Alkermes officials announced today. Separation between the groups began at 4 weeks from baseline and was maintained to the end of the 6-month trial.
The company also announced plans to submit a New Drug Application for the treatment, ALKS 3831, to the US Food and Drug Administration (FDA) in mid-2019.
ALKS 3831, an oral atypical antipsychotic, is a combination of olanzapine and samidorphan, a new molecular entity.
“Put simply, the study was an unequivocal success,” Craig Hopkinson, MD, chief medical officer and senior vice president of medicines development and medical affairs at Alkermes, said in a conference call with investors. “The results of the study were clear and strong.”
Alkermes chief executive officer Richard Pops said clinicians have “tremendous interest” in using olanzapine for patients with schizophrenia, but are reluctant to because of its weight gain profile.
“We have a fundamentally different drug now than olanzapine but we’ve captured its efficacy so that’s why we’re so pleased with the outcome,” he said.
The double-blind study, ENLIGHTEN-2, compared weight gain in 561 patients with stable schizophrenia. It had 2 coprimary endpoints: mean percent change in body weight and proportion of patients who gained 10% or more of their body weight.
The endpoints were designed in conjunction with the FDA, which required a P value for each comparison of less than .05, Dr. Hopkinson said.
The study found the olanzapine group (n=272) gained a mean 6.59% in body weight, 11.2 pounds, compared with a mean weight gain of 4.21%, 7 pounds, in the ALKS 3831 group (n=266). Among the olanzapine group, 29.8% had gained 10% or more of their body weight at 6 months, compared with 17.8% of ALKS 3831 group. Both comparisons had a P value of .003.
In the ALKS 3831 group, weight stabilized after 6 weeks and remained flat for the duration of the study. As seen in the phase 2 study of the drug, the weight gain curves for the groups began to separate after Week 4 and continued to diverge for the rest of the study.
The study also met its key secondary endpoint, the proportion of patients taking ALKS 3831 who gained 7% or more of their body weight at 6 months, 27.5%, compared with the proportion of patients taking olanzapine who did, 42.7% (P=001).
Similar results were found when analyzing the proportions of patients who gained at least 2%, 5%, and 15% of their weight, Alkermes officials reported.
Serious adverse events were reported in 3.6% of ALKS 3831 patients and 2.5% of olanzapine patients. The most common were weight gain and somnolence in both groups, dry mouth in the ALKS 3831 group, and increased appetite in the olanzapine group. Of the patients who received ALKS 3831, 64.2% completed the study, compared with 63.8% of patients who received olanzapine.
Alkermes plans to present full study results, including other endpoints and effects on metabolic parameters, at scientific meetings in spring 2019.