Alkermes' schizophrenia drug met its primary endpoints in a second phase 3 trial, setting it up for an FDA filing in mid-2019. Patients taking the drug gained less weight on average than patients taking olanzapine, the antipsychotic on which it is based.
Olanzapine is one of the most commonly prescribed treatments for schizophrenia, but can cause a number of side effects, including metabolic issues and extreme weight gain. Because of this, Eli Lilly, which markets olanzapine as Zyprexa, had to add a warning label indicating these risks in 2007. Alkermes’ candidate, ALKS-3831 combines olanzapine with samidorphan, an opioid antagonist designed to counteract these side effects.
"Significant unmet patient need remains in schizophrenia despite the number of treatment options available. A new agent that offers the robust efficacy of olanzapine but with a favorable weight profile that stabilizes within weeks of treatment initiation would be an important and differentiated addition to the treatment armamentarium for schizophrenia," said Christoph Correll, M.D., a professor of psychiatry and molecular medicine at Hofstra Northwell School of Medicine, in a statement.
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The ENLIGHTEN-2 study compared ALKS-3831 to olanzapine in 561 patients with stable schizophrenia, Alkermes said in the statement. It is the second of two phase 3 studies in the drug’s registration program. After six months of treatment, patients taking olanzapine had a 57% higher weight gain from baseline compared to patients on ALKS-3831. And olanzapine patients were more likely to put on greater amounts of weight—they had twice the risk of gaining 10% or more of their baseline body weight compared to patients on ALKS-3831.
The drug also met a secondary endpoint—just over a quarter of ALKS-3831 patients put on 7% or more of their baseline body weight after six months, while 42.7% of olanzapine patients did. The weight gain curves for each group started to diverge in the fourth week of treatment, with ALKS-3831 patients’ weight stabilizing in the sixth week and staying flat for the rest of the treatment period.
"These unequivocal results from ENLIGHTEN-2 provide evidence of a clinically meaningful, differentiated weight profile for ALKS-3831 compared to olanzapine. Importantly, ALKS-3831 favorably shifted the weight gain distribution curve compared to olanzapine, both in terms of mean weight gain and patients experiencing extreme weight gain," said Craig Hopkinson, M.D., chief medical officer and SVP of medicines development and medical affairs at Alkermes, in the statement.
Patients in both arms finished out the study at roughly the same rate, 64.2% for ALKS-3831 and 63.8% for olanzapine. The most common adverse events were similar in both arms, with both ALKS-3831 and olanzapine patients experiencing weight gain and somnolence, or drowsiness. Serious adverse events also occurred at similar rates: 3.6% for ALKS-3831 and 2.5% for olanzapine. The company plans to present full data from this study at an upcoming scientific meeting.
The data come shortly after an FDA panel voted against recommending the approval of Alkermes’ depression drug, ALKS-5461. Like ALKS-3831, it includes samidorphan to ward off the negative effects of another drug, buprenorphine, an opioid that has antidepressive properties.