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Treating food allergies: Is there light at the horizon?

Dietary elimination is currently the only way to treat food allergies. Unfortunately they have a huge, very limiting impact on the patients’ everyday life and there is an enormous fear of anaphylaxis. But there is light at the horizon! MeinAllergiePortal spoke to food allergy expert Hugh A. Sampson, MD, on new therapeutic options regarding diagnostics and treatments of food allergies. He is Professor of Pediatrics, Allergy and Immunology at The Mount Sinai Hospital in New York, USA.

Dr. Sampson, which methods for the treatment of food allergies are currently being developed?

Right now there are two forms of treatment that have completed phase-III-trials. One is epicutaneous immunotherapy, which is using a patch and was developed by DBV Technologies. The company has submitted their application to the FDA and is now waiting for review.

Another form of treatment of food allergies is an oral immunotherapy, developed by Aimmune Therapeutics. They have finished their phase-III-trial and just published a manuscript1) describing the study in The New England Journal of Medicine. I believe that Aimmune Therapeutics is planning on filing with the FDA before the end of the year.

Apart from those two, a variety of other therapeutic strategies are being researched.

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What else is being researched?

Another therapeutic strategy under development is a subcutaneous immunotherapy with a modified peanut protein, which is in a phase-I-trial.

Then there is LAMPVaxTM, a DNA-vaccine, that is in a phase-I-trial. LAMP stands for Lysosomal Associated Membrane Protein.

Another therapeutic path being researched is immunotherapy in combination with Omalizumab, respectively anti-IgE. A couple of small studies have been published, and a larger study is being initiated.

A study on oral immunotherapy with Dupilumab is starting as well. Before, Dupilumab was examined in respect to the treatment of eosinophilic oesophagitis (EoE). In current studies one addresses the question, if Dupilumab could be used for the treatment of peanut allergieslergies in combination with immunotherapy. The aim is to suppress possible adverse reactions and also to promote tolerance or a more sustained response than we can observe with traditional immunotherapy.

There also will be another study coming out utilizing nanoparticles. This means that peanut protein is incorporated into nanoparticles, which also contain DNA components. It is expected that these DNA components will lead to nanoparticles being taken up more rapidly by antigen presenting cells. This study is still in pre-phase-I-stage.

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Are all studies you mentioned targeting peanut allergy?

Most of the therapies researched are targeting peanut allergy. But these are more or less prototypes for future therapeutics.

Past peanut allergy studies have shown, that the protective effect of immunotherapy does not last beyond the end of treatment, is this also the case with, e.g., epicutaneous therapy?

Oral immunotherapy has been around for well over one hundred years, so there is a fair amount of experience. It has been shown that most individuals will lose protection after stopping therapy for a period of time.

It is not clear, whether or not epicutaneous immunotherapy will result in a more sustained response, because there are no long term studies beyond three years yet. The mouse models suggest, that the effect might be more sustained, but there is no data in humans, at this point, to support that.    


Is it possible to identify the fraction of patients that will not outgrow the food allergy or will one just have to wait until the child grows older and it becomes evident?

Diagnostic tests to distinguish these patients are being developed for milk and egg. For wheat this has not been done yet, so you will have to, basically, wait to know which group a patient belongs to.

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Which diagnostic tools are available to predict the patients risk for severe reactions, chance to lose the allergy in adolescence and success of immunotherapy?

There are two diagnostic tools that appear most promising at the moment. One is the epitope analysis, where one is looking at specific food protein epitope profiles, respectively the amount of IgE they have to various epitopes on that food protein.

The other diagnostic tool is the Basophile Activation Test (BAT). The test has a high diagnostic accuracy, it can be particularly helpful in cases where skin prick test and specific IgE are equivocal. Also it may allow reducing the need for oral food challenges.

Another test, called Mast Cell Activation Test, is in a very early stage of research.

But: All these diagnostic tools have to be validated with bigger studies.

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Are there any other risk factors for severe reactions?

There are some indicators that suggest that a patient might fall into a more severe category, but these are not accurate. Possible risk factors for severe reactions are, e.g., presence of poorly controlled asthma, a very high IgE-level to the particular food and multiple allergies.

Dr. Sampson, thank you very much for this interview!

 

Sources:

1)The PALISADE Group of Clinical Investigators, AR101 Oral Immunotherapy for Peanut Allergy, The New England Journal of Medicine, November 18, 2018, DOI: 10.1056/NEJMoa1812856, (https://www.nejm.org/doi/full/10.1056/NEJMoa1812856)

2)Nowak-Węgrzyn A, Wood RA, Nadeau KC, Pongracic JA, Henning AK, Lindblad RW, Beyer K, Sampson HA, Multicenter, randomized, double-blind, placebo-controlled clinical trial of vital wheat gluten oral immunotherapy, . Send to

3)J Allergy Clin Immunol. 2018 Oct 24. pii: S0091-6749(18)31294-6. doi: 10.1016/j.jaci.2018.08.041. [Epub ahead of print],(https://www.ncbi.nlm.nih.gov/pubmed/30389226)

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