Shifting the Treatment Paradigm of Severe Asthma With Novel Biologics - Episode 14

Novel Agents in Clinical Trials

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Sidney Braman, MD, and Geoffrey Chupp, MD, discuss other novel agents currently in clinical trials for the treatment of severe asthma.

Reynold Panettieri, Jr, MD: Sid, I think you know that we’ve covered this next query quite well. But is there anything you wish to add that you’re interested in? This was in other novel therapies in clinical trials. That piqued your interest. I think we’ve heard a bunch and I think you’ve alluded to some. Anything that you want to add at this time?

Sidney Braman, MD: No. I think you mentioned this, and I think this is going to be resurrected. I was disappointed at the NAEPP [The National Asthma Education and Prevention Program]/ NHLBI [National Heart, Lung, and Blood Institute] statement on thermoplastic-bronchial thermoplasty. If you look at the latest GINA [The Genetic Information Nondiscrimination Act] guidelines, they kind of pushed it aside. I think there is a group of patients, the non-T2 [type 2 asthma] patient—a patient who has severe persistent disease—and I think bronchial thermoplasty is an effective treatment. I know I’ve heard you speak about some of the fascinating things happening in smooth muscle when the thermal injury occurs, but I think that’s something that is going to probably emerge a little stronger in years to come, despite what the 2 groups have said. I think it was more of a caution rather than saying, “Don’t do it.”

Reynold Panettieri, Jr, MD: Geoff, you acquired a lot of the primary data for bronchial thermoplasty. You’ve been a proponent. Do you see it going away, resurrecting, or maybe having a more focused use?

Geoffrey Chupp, MD: Well, I think that what we’re looking at here is how it’s going to be used in the toolbox, in addition to biologics. Now that we are starting to attack the low T2 disease more effectively with biologic drugs, the subgroup of individuals who are more specifically candidates for bronchial thermoplasty alone is going to shrink. I think that. We also know from data that patients on biologics or receiving bronchial thermoplasty often do well when they receive both. So those people who get partial response to a biologic may also benefit from bronchial thermoplasty. As you know, Mario Castro, MD, director of the Clinical and Translational Science Institute at the University of Kansas School of Medicine in Lawrence, Kansas, has been looking at a more targeted approach to bronchial thermoplasty for airways that are showing poor ventilation by XeNA on gated MRIs. He has some good results suggesting that a more targeted approach, with 1 setting, may be more effective in people who have asthma in certain regions of the lung—more physiologically important—even though the whole lung may be inflamed. I definitely think that, hopefully, we will continue to have a role for this therapy. I agree completely with Sid that, and I wrote this in an editorial with Mario, that the NAEPP may have went a little too far or too restrictive in their guidance. I think we’re going to be seeing some interesting things in the alarming space. Analogous to what happened in the IL-5 [interleukin-5] space, we know the next target coming down the pipeline is probably in the IL-33 pathway with a receptor blocker, as opposed to a soluble cytokine blocker. We know that these alarms don’t have the same biologic effects. It’s going to be interesting to see how these drugs compare as they move through the clinical trial process. We also targeted the CRTH2 [chemokine receptor homologous molecule expressed on Th2 lymphocytes] receptor. These trials, unfortunately, failed in phase 3. Possibly because of the weaker effects of this target on biologically controlling disease, or the phenotype of the patient wasn’t correctly identified because there wasn’t a specific biomarker or endotypic biomarker that could be targeted.

Reynold Panettieri, Jr, MD: Yeah. That, and if we go back in time, like mepolizumab [Nucala] when it first was trialed. Mepolizumab failed because the participants that were enrolled in the study were far too mild for the disease and were too diffuse. When it was more focused, it became 1 of the first IL-5, anti-IL-5 that could be used in the United States. So a very good point.

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Transcript Edited for Clarity