Lawrence Severt, MD, PhD, discussed the results from the phase 3 ADVANCE trial of atogepant, and its effect on a number of patient-reported outcomes.
AbbVie’s atogepant, a small-molecule calcitonin gene-related peptide (CGRP) receptor antagonist, has continued to demonstrate its efficacy as a potential preventive treatment of migraine. Data from the phase 3 ADVANCE study (NCT02848326) showed that the treatment had a statistically significant improvement in monthly migraine days (MMDs) as compared to placebo.
In addition to observing atogepant’s impact on MMDs, researchers conducted a separate analysis that evaluated the effect of the drug on patient-reported outcome measures of activity impairment and headache impact. Compared with placebo, all 3 dose groups demonstrated improvement of function in Performance of Daily Activities and Physical Impairment domain scores across the 12-week treatment period. The study authors concluded that these results confirm the role of atogepant as a promising treatment among people with migraine.
Lawrence Severt, MD, PhD, currently serves a director at AbbVie and has been among the study investigators involved with ADVANCE. In the first half of an interview with NeurologyLive, Severt discusses the most notable findings from the study, along with the importance of patient-reported outcomes and the growing trend to utilize them more within the clinical and pharmaceutical community.
Lawrence Severt, MD: The important things were all incorporated into Dr. [Jessica] Ailani’s presentation. One of the biggest is not actually the primary end point, but is the 50%, 75%, and 100% responder rates that she spent some time on. Before COVID, I was still doing a volunteer clinic once a month. That’s on hold now, but hopefully I’ll get back to it. Thinking about ways that we can talk about our results to patients is important. Just as Dr. Ailani said, you can sit down with a person and say, “If you take this drug for several months, your chances of cutting your migraine attacks in half is 60% compared to 30% for placebo.” Although, most patients say, “I don’t care about the placebo, just tell me what the overall number is.”
The 50%, 75%, and 100% total migraine freedom results were definitely surprising to us. It will be very meaningful for patients to hear and understand as well as for clinicians to communicate. That’s 1 of the major points that came out. Our primary end point, the reduction in mean monthly migraine days was exciting to us, because we showed a robust effect and statistically significant result at all 3 of the doses. We think that will probably be impactful to clinicians. It’s a little harder for patients to look at that and say, “Well, 1.2 fewer days a month versus 1.7 or 0.8.’ It’s harder for them to conceptualize, but if you can sit down and say, ‘you have a 60% chance of cutting your migraines in half,” that’s easy to understand.
In our other abstracts, we spent a good amount of time developing patient reported outcomes, as well as trying to work with patient groups and doctors like Ailani who, are focused on this. We were able to meet all of those end points in the 2 highest dose groups, 30- and 60-mg. The 10-mg group did not meet the final end points. Even though they’re a little arcane, when clinicians read those scales, understand them, and are able to relay back that these patients were able to go to work or take their kids to their soccer game, it’s important to us. It’s important for the patient to be able to express his/her satisfaction with the drug, right? It’s great to meet an FDA-mandated end point, which we did in a robust way, but there’s a difference between scientific end point where you achieve statistical significance, versus listening to patients and understanding what is meaningful in their life.
The American Headache Society has endorsed the goal of migraine freedom for people with migraine. That’s 1 message that we heard loud and clear. We would like to assemble a portfolio of products that is able to advance the cause towards migraine freedom. To do that, we have to understand what it means to patients. Does it mean you have no attacks? You have almost no attacks? Does it mean you don’t have a migraine hangover after you have an attack? Are you able to work without sunglasses on because your computer screen is too bright? What is the goal of migraine freedom mean? The best way we can understand that is from a patient’s point of view and including these kinds of outcomes. To outline, the big things were that we had very impressive responder rates that are impactful and will be heard by clinicians and patients, we met our primary end point in a robust way, and that we had a substantial focus on these patient-reported outcomes?
Companies have done a better job and hopefully clinicians as well of including these patient-reported outcomes. As clinical medicine has transformed from a patriarchal, hierarchical model of 50 years ago, to a more collaborative, listening model on both sides, where the patient doesn’t just listen to the doctor but that the doctor also listens to a patient. That has shifted substantially in clinical medicine. It’s beginning to shift, we think, in scientific and pharmaceutical research. We realized that for patients to understand our drugs and understand the benefits they can bring them, as well as any potential safety concerns or adverse events, that it’s important to include these patient-reported outcomes.
We have whole groups within the company, as do most of the big companies, that are devoted to developing these outcomes. We have generated our own independent scales to look at the impact that migraine has on people’s lives. There are scales that are developed by the American Headache Society and American Academy of Neurology that also measured these outcomes. We looked at many of these to decide which ones would be the most impactful on people’s lives and then incorporate those into the trial. It’s definitely changing. More companies are listening to this, and the FDA and regulatory bodies have realized that this is something that patients deserve and want. Patients are not willing to sit back anymore, and they shouldn’t. They should be able to express what they need from their doctors and their medications. We’ve made quite good progress in these atogepant trials in doing that.
I think we have a winner. We think it’s a very good drug. People have had oral preventives for a number of years now. We listened to the patients with migraine and heard that they were dissatisfied, and they wanted other options. The monoclonal antibodies that have emerged in the past 3 or 4 years have worked for many people and are liked by many people, but we also heard from the patients themselves that they would like to have an oral option that they don’t have to inject. That gives them more flexibility of daily dosing versus monthly. We listened and heard what the people were telling us, and hopefully we’re going to be able to provide them with another treatment option.
Transcript edited for clarity.