- Alkermes aims to submit an experimental schizophrenia drug for U.S. approval by mid-2019, announcing Thursday the success of a second Phase 3 study needed to support its application to the Food and Drug Administration.
- Results from the trial, which assessed the effect of Alkermes' antipsychotic on weight gain, are a dose of good news for the drugmaker, which was set back earlier this month in its bid to win support of an FDA advisory panel for another of its drug candidates.
- ALKS 3831, as the schizophrenia drug is known, combines the active ingredient of Eli Lilly's Zyprexa with a novel opioid antagonist Alkermes has developed. The drugmaker aims to position ALKS 3831 as similar to Zyprexa in efficacy, but without the weight gain known to be a side effect of Zyprexa.
Alkermes needed a win. Coming into the fall, the pharma hoped to make progress with its two most advanced drug candidates: ALKS 5461, for the treatment of major depressive disorder, and ALKS 3831 for schizophrenia.
A negative vote from an FDA advisory panel on Alkermes' case for ALKS 5461, however, looks to have put an approval for that drug out of reach, barring a surprise decision from regulators. That's shifted the weight of investor expectations to ALKS 3831, which had succeeded in showing a positive antipsychotic effect its first Phase 3 study in June 2017.
In the second late-stage trial, dubbed ENLIGHTEN-2, Alkermes pitted ALKS 3831 directly against Zyprexa (olanzapine), measuring the effect of each drug on weight gain over six months among patients with stable schizophrenia.
Topline results presented Thursday show trial participants on ALKS 3831 experienced lower average percent weight gain than those on Zyprexa, Alkermes said. Additionally, a lower proportion of patients on the experimental drug gained 10% or more of their baseline body weight at six months compared to the control arm.
Alkermes noted curves representing weight gain in each group began to separate after 4 weeks, with that of ALKS 3831 stabilizing and remaining flat through six months.
Mitigating the weight effects of Zyprexa could make Alkermes' drug a more attractive option for patients and physicians — an advantage that the company is counting on to make its case for ALKS 3831.
"We have a fundamentally different drug now than olanzapine, but we've captured it's efficacy," said Alkermes CEO Richard Pops on a Thursday conference call discussing the study results.
Alkermes believes ALKS 3831 works by normalizing the reward pathway in the brain tied to food consumption, which Zyprexa is thought to amplify. ALKS 3831 also appears to improve glucose clearance, giving it a potential metabolic effect.
Not all patients avoided weight gain, however. The most common adverse events for the ALKS 3831 arm were weight gain, somnolence and dry mouth.
With positive data now in hand, Alkermes will meet with the FDA with an aim to file a New Drug Application by the middle of next year.
Key questions on ALKS 3831's commercial prospects remain, however, and could dampen investor enthusiasm for Alkermes.
For one, ALKS would enter as a branded drug in a therapeutic market with existing generic options, including Zyprexa. Leerink, an investment bank, believes Alkermes could eventually earn between $500 million and $750 million in peak annual sales for ALKS 3831, but notes that payer agreement on reimbursement will be "very difficult."
Additionally, physicians concerned with Zyprexa's effect on weight gain have other options with less pronounced effects on weight, Leerink wrote in a note to investors earlier this month.