Neil Graham, MD, MPH: The Potential of Biologic-Allergen Combination Therapy


The Regeneron VP explains how dupilumab could possibly serve as a complimentary therapy to Aimmune's investigative food allergy therapy.

A pair of burgeoning therapies in the allergy/immunology field could eventually improve the state of food allergy care.

Monoclonal antibody dupilumab (Dupixent), Sanofi-Regeneron’s biologic indicated and investigated for care in primarily type 2 inflammation-associated diseases, and Aimmune Therapeutic’s investigative oral peanut allergen AR-101, are being assessed as a combination therapy for patients with peanut allergy.

What Neil Graham, MD, MPH, hopes is that the combination brings food allergy patients a more optimistic treatment outcome. In an interview with MD Magazine® at the Academy of Allergy, Asthma & Immunology (AAAAI) 2019 Annual Meeting in San Francisco, CA, Graham, vice president of Strategic Program Direction, Immunology & Inflammation, for Regeneron, explained how a interleukin (IL)-pathway blocking biologic like dupilumab could benefit the gradual effects of a food allergen.

MD Mag: How could a food allergy patient potentially benefit from a biologic-allergen combination therapy?

Graham: It's not as simple as it seems. The problem with allergens is that you have to start very low, because the patient can have anaphylaxis. They can die. It's very dangerous—they're highly sensitized to it.

So, one option is to start low with the various miniscule doses of the peanut. You gradually, over a long period of time—it could be a year—get up to a stage where they could switch from an IgE response to an IgG response, and lead to tolerance to that particular allergen. So, you've got a safety issue, you've got a timing issue, and then one of the problems with the peanut allergen is you actually can induce eosinophilic esophagitis, ironically.

So, dupilumab in some ways is a perfect thing to use with that kind of therapy, because we hope—we don't know for sure, because we haven't done it—that we can reduce the reactability to the antigen, reactability to anaphylaxis and other symptoms. And we also know from our data that we probably can reduce the eosinophilic esophagitis side effect, and we also are hoping we can accelerate how quickly you can go up with the allergen. So, that's one of the things we're going to be testing.

And then, finally: can we actually improve the results of the allergen. And we don't know for sure, because, surprisingly it's still that the basic biology of the treatment of allergies is still not completely well known.

We believe is a big role to be played of the IgG/IgE role. But there's also perhaps, on the T-cell side of the equation, there's something we can learn there as well. And that's one of the things we're going to be studying.

So that's how it would work. I think it will prove it can hopefully accelerate the allergen and the tolerability. It would be a real synergy between 2 different treatment modalities.

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