Neil Graham, MD, MPH: Tracking Dupilumab Along Inflammatory Discoveries


The biologic's indications for inflammatory diseases are greatly varied and still developing, and it owes some of that to recent advances in disease prognosis.

It wasn’t long ago that Regeneron Pharmaceuticals switched its allergic/immunologic clinical focus from the ligand to the interleukin pathway. Neil Graham, MD, MPH, vice president of Strategic Program Direction, Immunology & Inflammation, for Regeneron, recalled the progress made in his 9 years with the organization after this switch.

In an interview with MD Magazine® at the American Academy of Allergy, Asthma & Immunology (AAAAI) 2019 Annual Meeting in San Francisco, CA, this week, Graham explained how the interleukin (IL)-targeting monoclonal antibody dupilumab came from this switch, how it was vindicated by successive marketing approvals for 2 different indications, and what else the company is looking to treat with it.

MD Mag: How have advances in inflammatory disease prognosis benefitted the clinical advancement of dupilumab?

Graham: I think that's the probably the big take-home from this particular drug and particular pathway. The research for Regeneron on this pathway goes way back to the 90s, when the company had a different molecule that that never got funded and didn't go anywhere. And then we saw follow-up studies with IL-4 ligand blockers by themselves and IL-13 ligand blockers which didn't really work—particularly in asthma, but also in AD (atopic dermatitis).

And eventually, when Regeneron came and focused on the receptor—it's a particular IL-4 receptor—it’s an elegant mechanism, because you can block both IL-4 and also IL-13 by targeting 1 receptor. So, that was very good. And then, as we started to dig more and more into each of the indications, we realized that the IL-4 and 13 pathway is elevated in many, many atopic allergic diseases. Now, of course, we know them today as type 2 diseases.

The science has come a long way just in the last 9 years I've been working in the area. And this drug is positioned, we think very nicely, to meet most of those indications, potentially. Now, this is I think no longer just a hypothesis—because we have an indication for atopic dermatitis driven by IL-4 and 13, for type 2 asthma driven by IL-4 13 and now CRS (chronic rhinosinusitis) with it nasal polyps. We always felt that would be the real proof of the pudding, because you have essentially 3 different conditions in the same patient, all of which we think are type 2—and we now know are type 2 because dupilumab works for all of them.

So what is now clear is that these are central pathways in many different diseases. So, we're exploring others. We're going to explore other respiratory conditions, we will explore other dermatological conditions, we're looking at food allergy, peanut allergy, eosinophilic esophagitis. All of these studies are ongoing at Regeneron in Santa Fe at the moment.

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