Braeburn on BRIXADI® Research and Addressing Fentanyl's Impact on OUD

Can you elaborate on the significance of the data, from the Phase III trial recently published in JAMA, for understanding how BRIXADI® compares to sublingual BPN/NX in this specific patient population, given the growing prevalence of fentanyl in the opioid crisis?

I want to start out, since we're talking about BRIXADI®, by telling your viewers that BRIXADI® is indicated for the treatment of moderate to severe opioid use disorder in patients who have either initiated with a single dose of transmucosal buprenorphine, or who are already being treated with buprenorphine. And it should be used as part of a complete treatment plan that includes counseling and psychosocial support. I also should let you know that it is distributed under a restricted rems distribution program, and the reason for that is that BRIXADI® does have a black box warning there is a risk of serious harm or even death if the medication were to be injected intravenously, it's supposed to be injected subcutaneously, and because of that, it should only ever be administered by a healthcare professional. So now to your question about the study that we published.

So, this was part of a larger Phase III pivotal trial for BRIXADI®, where BRIXADI® was studied head to head against sublingual buprenorphine and naltrexone. And the goal of the study was to show whether BRIXADI® was non inferior to sublingual buprenorphine in the treatment of opioid use disorder, we did find in that study that that BRIXADI® was non inferior to sublingual buprenorphine in the primary endpoint of responder rate of negative urines and was actually found to be superior to sublingual buprenorphine in the percent of negative opioid assessments from weeks four to 24 as measured by the cumulative distribution function. This analysis that we put out a couple weeks ago now was a post hoc analysis of that pivotal study, and what it did was it looked at patients who either tested positive for fentanyl at the baseline visit, when they first started the study, or tested negative for fentanyl.

So, we took those two subgroups of patients and looked at the outcomes in those patients on a post hoc basis, and what we found was the results in those two subgroups were similar to what we had seen in that overall study, so comforting that in both subgroups, regardless of fentanyl status at baseline, we found similar outcomes to the overall main study.

The study was post-hoc in nature. How confident are you in the generalizability of these findings to a real-world treatment setting for OUD patients struggling with fentanyl misuse?

It's a really important question. Thanks for asking it. There are some limitations to this study, as there are with any post hoc analysis. One of them is that patients at the time likely believed that they were taking heroin, that heroin was mixed with fentanyl. This was early in the time period where we started to see fentanyl entering the drug supply. That's why we wanted to evaluate fentanyl in the study, and it was the first time a phase three study had evaluated fentanyl at baseline in patients entering the study, and so because patients believed they were primarily using heroin, and we can't say how much fentanyl was in their drug supply, as opposed to now, when patients are primarily using fentanyl and know that they're using fentanyl, that does affect the generalizability to patients now that being said, knowing that patients did test positive for fentanyl, and we believe that potentially those patients had a more severe state of their opioid use disorder as a result, that there is some information that we get from looking at this on a post hoc basis.

The other thing I would say, and this is important too, for a post-hoc study, that the study was not powered to look at these subgroups. We didn't initially intend to look specifically at these subgroups, but given the rise in fentanyl. Since the study was conducted, we thought it was important to understand what was going on in patients who did test positive for fentanyl versus those who did not.