The assessment does point to a path for approval, however FDA staff do raise some concerns about the fact that the drug’s makeup includes an opioid antagonist.
Shares of Alkermes climbed more than 6% Wednesday after the U.S. Food and Drug Administration (FDA) released its assessment of the company’s schizophrenia and bipolar drug ahead of an advisory committee meeting scheduled for Friday.
The assessment points to a path for approval, however FDA staff members did raise some concerns about the fact that the drug’s makeup includes an opioid antagonist. Ireland-based Alkermes is aiming for approval of ALKS 3831 (olanzapine/samidorphan), a once-daily oral antipsychotic drug candidate for the treatment of adults with schizophrenia and for the treatment of adults with bipolar I disorder. The drug is a combination of samidorphan, an opioid antagonist that is a new molecular entity and Eli Lilly’s Zyprexa. Alkermes paired well-established schizophrenia medication, initially approved in 1996, with the opioid antagonist as a means of controlling weight gain and other side effects that have been commonly established to the Eli Lilly drug. Weight gain is a concern for patients taking second-generation antipsychotics like Zyprexa due to its relationship to metabolic syndrome.
In its briefing documents for the advisory committee, the FDA notes potential safety risks from the inclusion of samidorphan that must be considered by members. Specifically, the FDA pointed to withdrawal concerns for people who have an opioid dependency and concerns over a reduced painkilling effect in patients who are already taking opioids. There is also a concern for potential opioid overdose if patients attempt to take more opioids than normal in order to overcome these issues.
Alkermes said it could address these concerns in the labeling for the drug if approved. The company also noted that it could create a communication plan that would alert potential prescribing doctors about the safety concerns. The advisory panel will meet Friday to discuss the issue and recommend whether or not the FDA should approve the drug for patients. The decision of the advisory committee is not binding to the final regulatory decision.
Alkermes submitted its New Drug Application for ALKS 3831 last fall. The NDA included data from the ENLIGHTEN clinical development program in patients with schizophrenia, as well as pharmacokinetic bridging data comparing ALKS 3831 and Zyprexa. The ENLIGHTEN-1 study evaluated the antipsychotic efficacy of ALKS 3831 compared to placebo over four weeks, and the ENLIGHTEN-2 study assessed weight gain with ALKS 3831 compared to olanzapine over six months. The Phase III ENLIGHTEN-2 study met its primary endpoints of a lower mean percent weight gain from baseline at six months compared to those receiving olanzapine, and a lower proportion of patients who gained 10% or more of their baseline body weight at six months compared to the cohort receiving olanzapine.
Early last year, Alkermes was stunned when the FDA rejected ALKS-5461, a treatment for major depressive disorder. The company went through a tumultuous period to get that medication to the FDA. In April 2018, the FDA accepted Alkermes New Drug Application (NDA) for ALKS 5461, only weeks after the regulatory agency rejected the NDA.
