FDA documents raise opioid abuse potential but pave a path toward badly-needed approval for Alkermes
Alkermes’ latest attempt to get an in-house drug past the FDA seems to be going better than the previous one.
The agency released their assessment of ALKS-3831, the Irish biotech’s experimental drug for schizophrenia and bipolar I disorder, ahead of an advisory committee hearing Friday. And while FDA reviewers flagged at least one key issue, the documents overall point to a far easier path to approval than Alkermes faced the last time they went to regulators, when the rejection of a controversial opioid for depression helped trigger layoffs and a strategic shift at the Richard Pops-led company.
“They read fairly benign,” Evercore ISI’s Umer Raffat wrote in a note to investors. “This bodes very well for ALKS heading into the AdCom.”
ALKS-3831 belonged to a long-running Alkermes strategy to repackage existing blockbuster medications in ways that made them safer or more appealing. In this case, that meant combining the Eli Lilly anti-psychotic Zyprexa with an opioid antagonist in an effort to mitigate the weight gain the current drug can cause.
Potential sales for the drug are moderate – SVB Leerink’s Marc Goodman pegged peak sales between $250 million and $300 million – but an approval would be key for a company whose stock has fallen 75% over the last two years amid FDA rejections and marketing practices the agency said violated standards.
Among the key questions that mix posed for the FDA was what it would mean for patients who used opioids. Reviewers noted that it could lead to withdrawal in opioid-dependent patients, or block the pain-relieving effects of opioids in settings and for people who need it. It could, they wrote, even lead to overdose if someone tried to overcome the effects of the antagonist.
Alkermes excluded opioid users from their trials and have proposed slapping a label that tells doctors not to prescribe the drug to those taking opioids. The FDA, though, pointed to data that showed other drugs not supposed to be given to opioid users were in fact prescribed to them as much as 11% of the time, “suggesting that despite the proposed labeling in olanzapine/samidorphan, concurrent use of opioids could occur in the patient population.”
The FDA didn’t take a definitive stand on whether good labeling could resolve these concerns, but analysts saw their discussion as encouraging for Alkermes.
The comments “were fairly balanced and not as negative as it could have been,” SVB Leerink’s Marc Goodman wrote in a note to investors, adding that the agency appears to see the risk as confined to just a subset of the patient population.
There were two other concerns, as well, including whether Alkermes adequately characterized the rest of the safety profile for the drug. The agency largely agreed that there appeared to be no new safety issues not seen in Zyprexa.
More pressing, Goodman wrote, was the question of how the FDA would view the weight gain data. The FDA has clear benchmarks for what warrants approval of a weight loss drug. Alkermes, though, was not trying to show that ALKS-3831 induced weight loss but rather that it didn’t cause weight gain, and it was unclear how the FDA would treat their data.
The FDA acknowledged that the two goals were different, telling advisors they can use the weight loss standards as a “reference” but that it “does not represent the standard for establishing the contribution of” ALKS-3831. Still, they left open questions about how beneficial the drug was, noting that, while it curbed weight gain in studies, it missed on other metabolic endpoints.
The committee will convene Friday to discuss the question, with an FDA decision due by Nov. 15.