Why it may be critical to reassess dosing practices being practiced in investigative food allergy therapies.
Not all practices should be adopted from groundbreaking work. In an interview with MD Magazine® while at the American Academy of Allergy, Asthma & Immunology (AAAAI) 2019 Annual Meeting in San Francisco, CA, this week, Brian Vickery, MD, explained how a poor, unevidenced dosing regimen has burdened recent phase 3 food allergy immunotherapy trials.
Vickery, an Associate Professor of Pediatrics at Emory University and Director of the Food Allergy Center, Children’s Healthcare of Atlanta, told MD Mag that the fairly traditional and critical dose-finding trials never preceded trials assessing the safety and efficacy of oral immunotherapies—drugs which are now nearing consideration for US marketing.
The result could be a worsened rate of anaphylaxis, or simply more treatment failure, in real-world settings.
MD Mag: What are the concerning trends found in recent oral immunotherapy trials?
Vickery: I think it's interesting that for most treatments we use, there have been dose-finding studies to try to identify what is an appropriate regimen to use. And that's a typical part of development and early-stage research, and that has never been done with food immunotherapy.
So you have lots of studies that have just sort of arbitrarily picked different doses, and people that that are practicing this in the community now sort of arbitrarily pick different doses. We actually haven't really worked out what an optimal regimen looks like. The regimen that was tested in the phase 3 study for AR-101 will likely go forward, but even that was developed based on preliminary studies that were themselves quite arbitrary.
I'm really interested in this concept: there was a recent study that came out from Germany using a product other than AR-101, but with a target maintenance dose that was about one-third as big and with a much, much slower dosing process. It showed that the safety of a low-dose approach was very different than what is seen in other studies. In other words—much better, fewer systemic allergic reactions, no eosinophilic esophagitis, very low rates of dropout, just looks very different than other OIT studies.
And conversely, we have data from people treating patients in the real world with very high doses of OIT that shows you get toxicity. You have people who are well into their maintenance regimens having anaphylaxis and using epinephrine, because they're taking 2 grams or more per day—which is almost like a little food challenge every day. And you have people reacting.
We have these quite wide range of doses that are being either tested or used, varying by orders of magnitude, and it's all empirical. We don't know what the right regimen is, and I think that's something that really needs to be worked out rigorously.