NCHR’s Statement at FDA Advisory Committee Meeting on Olanzapine and Samidorphan Combination Tablets

October 9, 2020


Thank you for the opportunity to speak today on behalf of the National Center for Health Research. I am Dr. Meg Seymour, a senior fellow at the center. Our center analyzes scientific and medical data to provide objective health information to patients, health professionals, and policy makers. We do not accept funding from drug or medical device companies, so I have no conflicts of interest.

We agree that weight gain and metabolic risks is a major problem with atypical antipsychotics, because of the health risks and because weight gain can result in patients discontinuing their medication. Although ALKS 3831 studies suggest that fewer patients taking the drug gain more than 10% of their baseline body weight than those taking olanzapine alone, we have concerns regarding its safety compared to an absolute difference between the groups below 14% and perhaps as little as 12%. The risk to benefit equation is particularly questionable because most of the patients in the weight gain study were male, Black, overweight at baseline, and were adults 55 years old or younger. None of us can predict how generalizable these findings would be for most patients who take antipsychotics, many of whom are White, some of whom are women, and many of whom are teenagers or over 55.

As the FDA scientists noted in their review, there is a considerable risk that as an opioid antagonist, samidorphan may lead to opioid withdrawal symptoms or to accidental overdose. Regardless of whether patients are prescribed an opioid or are abusing them, these risks are present. These risks are especially concerning for patients with bipolar disorder, who are more likely to be abusing opioids than the general population.

Labeling alone is not enough to mitigate these risks. Patients and providers deserve actual data on the safety of the drug for those with opioid dependence. It is not enough to assume that patients and prescribers will heed or understand the warnings of a label. Although fewer than 14% of patients may benefit from this drug by experiencing lower weight gain, the risks are too high to justify approval.