Advances in the Management of Prurigo Nodularis - Episode 15

Emerging Treatments for PN

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Drs Raj Chovatiya, Shawn Kwatra, and Sarina B. Elmariah review exciting new therapies in the treatment landscape of PN.

Raj Chovatiya, MD, PhD: That’s what excites me, and that leads into my next question. I want to bounce it back to Shawn. You mentioned nemolizumab. Can you tell me a little bit more about that? What it is? What have some of the findings shown? What does the potential hold another therapy for PN [prurigo nodularis]?

Shawn Kwatra, MD: Nemolizumab is a monoclonal antibody targeting IL-31 receptor A. Phase 2 data have already been published in the New England Journal of Medicine. We know that this is a very effective agent that’s in development. We know that only a few doses of the drug can reduce itch intensity very quickly, within a matter of a few days. Also, the depth of response is also very significant. In the phase 2 trial of nemolizumab for prurigo nodularis, patients were followed, and around 10 weeks later, they had approximately a 50% reduction in their itch.

The nemolizumab clinical trial program has invested in a few things. The first thing is in addition to the 2 pivotal phase 3 trials; they’ve also invested in a multiyear extension study, a durability study. The main questions patients had are, “I’m on the therapy. I’m on a biologic. Does this mean I’m on a biologic forever? What happens if I come off?” I think that the fact that they’re investing in getting data is going to be very important for us when we’re counseling patients about if they get off therapy, what to expect. Many folks understandably are a little bit hesitant to have continuous long-term therapies. That’s 1 of the considerations I think that’s going to give us more data about the drug from the phase 2 data. The public release of some of the phase 3 data is very strong as well. It’s going to be another great option for patients with prurigo nodularis.

Raj Chovatiya, MD, PhD: It’s interesting because we were looking at this drug through a very atopic dermatitis lens for a period of time, just given some of the work that had come out of the Japanese population and the approval there where it’s specifically approved for the pruritus associated with atopic dermatitis. I think that there was a little bit of reluctance among the AD [atopic dermatitis] community where they thought, OK, this seems to be a medication that’s working reasonably well for the itch, but by and large, for our conventional atopic dermatitis measures, is it really going to get us where we want it to? It’s very encouraging to see what’s happened as far as prurigo nodularis goes. I’m, personally very excited to see how this pushes the field forward in terms of a different therapeutic target, and one which I think is going to teach us a lot about IL-31, which we always talk about as the itch cytokine, but have not had any real-world practice in directly targeting, which is going to be super cool. That’s not the only new thing coming out, there are others. Sarina, I’ll pick and choose a couple that have at least some data out there. Maybe you can share your thoughts. You mentioned nalbuphine earlier, very briefly. Maybe you can tell the audience a little more about that, where you see that panning out.

Sarina B. Elmariah, MD, PhD: Thanks Raj for that question. I mentioned before, nalbuphine is a new kappa opioid-antagonist combined medication. It is an oral extended-release medication that has been used in the past for pain, and now is being used to manage itch in prurigo nodularis. It’s in phase 2, phase 3 trials and has been showing promising results. I think that this drug and targeting this access may be helpful not just for prurigo nodularis but really thinking about how itch is involved in the process of neurosensitization and other itching disorders as well. I think it holds a lot of promise for PN but also for the broader landscape of itch.

Raj Chovatiya, MD, PhD: Shawn, any thoughts on an oncostatin-M receptor beta. Since we talked about IL-31, tell me what you think of vixarelimab.

Shawn Kwatra, MD: What’s fascinating is, we have a few public data releases with vixarelimab. Which targets oncostatin M receptor beta. That’s going to modulate oncostatin M signaling IL-31 as well. In atopic dermatitis, modulating oncostatin beta helped with the itch, but it didn’t necessarily help with the lesions vs prurigo nodularis. What we’re finding is it’s helping more with resolving the nodules. It comes down to more of the questions: What is dominant in atopic dermatitis? What is dominant in prurigo nodularis? Is it the itch? Is it the lesions, the subclinical inflammation? What we know in PN is the itch is truly a driver of disease severity, whereas the drug vixarelimab didn’t have much of an effect in AD, although in prurigo nodularis it seemed to work. I think that sheds light in terms of the biology of the disease as well.

Vixarelimab has some data that have been released about nodular resolution and itch. I believe Genentech acquired the compound from Kiniksa Pharmaceuticals and they’re going to be moving forward with the development for that compound. I know that Sarina talked about nalbuphine, and we had some data released that put it firmly behind the monoclonal antibodies because it was just more of a modest effect. I think the power in the study was that it had so many folks in it. If I had to look toward the future it would be more of an adjunctive therapy second-line agent.

I agree with Sarina in terms of I’m more excited about that access, especially for neuropathic pruritus, which is such a difficult problem targeting immune kappa opioid access. Also, just as an adjunctive H therapy. I think that can be a helpful option for patients. Sometimes I use the ipratropium nasal inhaler, which is a kappa opioid agonist. However, I’m always a little worried about adverse effects. Sometimes folks can have sedation or nausea or any of those types of GI [gastrointestinal] adverse effects. I think we’ll learn more from the data release. Always having new therapies is going to be helpful.

I will also mention there’s a subtype of PN that is more skewed toward neuropathic. They just don’t have any biomarkers of type 2 inflammation. I think that in that patient population, in particular, that would be a great role for nalbuphine. In addition, there are some JAK [Janus kinase] inhibitors. The insight has a JAK1 inhibitor that’s in global trials, a phase 2 dose-ranging study. As we know, our group also showed that PN IL-22 plays an important role. It’s really from CD4 [cluster of differentiation 4] and CD8 T-cells. It’s also involved in skin thickening similar to what we see in Black patients with atopic dermatitis. I think there are certainly reasons to believe a JAK1 inhibition would be an important mechanism of action. Those are the key drugs.

What I’m looking for in the future is, what about the drugs that are making their way through atopic dermatitis that may also work? We know that there are phase 2 trials that are going on with OX40 [CD134] inhibitors. We know that topical JAK inhibitors were approved for atopic dermatitis. That would be one therapy worth exploring in PN, especially from a topical level. That’s the overview of agents that we have in development right now.

Transcript edited for clarity