Novel Therapies Under Investigation in Asthma

This is part of the MD Magazine^® Peer Exchange, “Precision Medicine in the Treatment of Severe Asthma.”Click here for Segment 17 and learn about interpreting research developments in asthma.

Peter Salgo, MD: Let’s talk about some other novel agents. We’ve got pitrakinra. What is that? These are all in development, down the pike, right?

Raffi Tachdjian, MD: Correct. There is a lot of stuff coming out of the pipeline—IL-33, IL-31, TSLP [thymic stromal lymphopoietin] blockers. Correct me if I’m wrong: They’re all sort of in phase I, phase II studies at this point.

Peter Salgo, MD: Pitrakinra is inhaled. No needles.

Neal Jain, MD: Pitrakinra is an IL-4, IL-13 antagonist that’s inhaled. It has completed a phase II trial that demonstrated some efficacy. I wouldn’t say that the efficacy was on order with what we’ve seen with some of the biologics, but it does seem to reduce exacerbations. It might be another option should the phase III trials…

David Rosenstreich, MD: It might be a nice adjuvant, as well, because it is inhaled.

Neal Jain, MD: An adjunct, right. At some point, I think the question becomes: Do these replace inhaled steroids or other therapies as personalized agents?

Peter Salgo, MD: Please say yes.

Neal Jain, MD: I hope so.

Peter Salgo, MD: What about tezepelumab?

Neal Jain, MD: That’s an anti-TSLP agent. If you think about what happens in asthma, as we were talking about, it starts with the epithelium. The epithelium becomes insulted by something—pollution, allergens, viruses, etcetera. And you have this group of cytokines called alarmones, which include IL-33, TSLP, IL-25, that then, downstream, cause all this other inflammation. That is an agent that blocks TSLP, so it’s a step up from IL-4 and IL-13.

Peter Salgo, MD: It’s way upstream.

David Rosenstreich, MD: It’s upstream.

Neal Jain, MD: Right. Phase II trials have been completed on this. A phase III trial is under way. We will see, but it looks to be an effective medication as well.

Peter Salgo, MD: Then we have 2 others here that are the monoclonal antibodies—lebrikizumab and tralokinumab.

David Rosenstreich, MD: They’re anti—IL-13s. Dupilumab is anti–IL-4 and anti–IL-13. These are focused on anti–IL-13. But as far as I know, they’re just not doing too well.

Neal Jain, MD: Both have phase III trials, and both phase III trials failed to meet their primary endpoint. So these are essentially no longer being pursued for asthma. They are looking at potentially using them in atopic dermatitis.

Peter Salgo, MD: And what about CRTH2 receptor antagonists?

Neal Jain, MD: What’s interesting is there are a lot of other targeted therapies that are inhaled or oral. CRTH2 is an oral antagonist. There are also JAK1 inhibitors and some PDE4 [phosphodiesterase 4] inhibitors. They tend to be oral or inhaled, and they target specific pathways in immune cells in the transcription of mediators in the inflammatory response. There are a couple of phase III trials going on looking at CRTH2 antagonists, and I think we will see. The phase II trials looked good. We’ll see what the phase III trials are like.

Transcript edited for clarity.