While for most individuals, picking a restaurant to dine at could simply be based on what they might be craving at the moment, for about one to five per cent of the world’s population, this is a well-thought-out decision that involves ensuring there wouldn’t be any cross-contamination in the food which is bound to trigger an allergy attack.
For Pharis Mohideen’s family, this has always been a concern. Mohideen, a father of two sons allergic to peanut and tree nuts, recounts that even when applying to colleges, checking with the food staff to verify that the canteen has a food allergy policy in place, was critical to where his children went.
“If you can’t eat, you can’t go to college. So it sounds like an exaggeration, but if you have lived it, the concern and worries and fears that parents and caregivers have about accidental exposure, it’s massive,” said Mohideen, who, as the chief medical officer (CMO) of global biopharma DBV Technologies, is working towards developing immunotherapies to treat food allergies.
As part of DBV’s mission to advance epicutaneous immunotherapy, its novel platform Viaskin aims to deliver drugs through the skin to target food allergies, peanuts in particular.
“So the concept here is we use the skin as the conduit to get the allergen into the body, as opposed to oral intake or injections. And the way the technology works is really ingenious,” said Mohideen.
DBV’s immunotherapy for food allergy to peanuts
The technology, which is an epicutaneous immunotherapy patch, consists of a quarter-sized foam ring – about 2 millimeters wide and thick – where 250 micrograms of the allergen, which is about 1/1000th of a peanut kernel, is electrosprayed. With a band-aid-like plastic film on top of the ring which goes on the individual’s back, the peanut protein does not directly come in contact with the skin. Instead, due to the body’s natural water loss, the protein is absorbed by the epidermis – the outermost layer of the skin. The protein is then captured by Langerhan cells, which are antigen-presenting cells – meaning that these cells can detect foreign molecules and activate immune cells – and carry the allergen to the lymph nodes. Upon arrival at the lymph nodes, specific T cells get switched on and induce an allergic response, thus desensitizing patients to peanut protein.
“There are two concepts going on here: In animal models, we don’t have systemic exposure to the protein because it’s so small, such small amounts, and it’s taken up by these antigen presenting cells. And so that does two things, it still allows the immune response to take place, but at a much safer level, because you’re using such small amounts of peanut protein exposure every day. So, over the course of three years of therapy, you’re exposed to a total of one peanut kernel – one peanut kernel is about 250 to 300 micrograms… The mechanism is like nothing on the market today,” said Mohideen, whose company also strives to combat intolerance to cow’s milk as well as eggs – both prevalent food allergies – employing the Viaskin platform.
With a focus on therapeutic measures for children, the food allergy immunotherapy company is advancing its pipeline after its placebo-controlled phase 3 EPITOPE clinical trial for one- to three-year-olds with peanut allergies reaped positive results. Along with studies on toddlers, trials are being conducted for various age groups, with the REALISE study for four- to 11-year olds and a separate trial for adolescents and adults, where the size of the patch differs in each category.
Could the Viaskin platform target multiple food allergies?
Meanwhile, DBV Technologies has also completed a phase 1/2 study for their immunotherapies to treat food allergy to milk, and has phase 2 lined up for next year. Having proven its success in a proof of concept study for eosinophilic esophagitis (EoE) – an allergic condition that targets the esophagus – a few years ago, the milk patch is hoped to achieve a promising outcome.
Leveraging the mechanism behind the platform could help tackle multiple indications, according to Mohideen. “The beauty of the product is that we can take that exact same patch, use it for cow’s milk allergy, and then use it for something else like EoE. And then in our pipeline, you can imagine, we can put just about anything that you want on the product. So cashew, sesame, all of the other food allergens are definitely in play, down the road. Obviously, we want to be focused and get peanut across the line first, and then we’ll slowly build in some of these other indications.”
While the clinical trials have established Viaskin’s safety, Mohideen explained that one of the most common side effects to the patch is the occurrence of local application site reactions. As many of the target patients have eczema and asthma, and as a result have sensitive immune systems, the therapy has caused reactions at the site of the patch. With low rates of anaphylactic reactions, Mohideen stated that the side effects are typically managed with a shot of epinephrine.
Despite the therapy, which is to be administered over a period of around three to five years – the longer the duration, the stronger the response – being able to elevate the protection from the intake of minute amounts of the allergen, it is however, not a cure. Mohideen describes it as an airbag in a car, a kind of safety net if an accident were to happen, or in this case, when accidental exposure to an allergen occurs.
Mohideen said: “What we tried to do is raise the amount of peanut protein that a patient can tolerate. So they don’t have an accidental exposure that leads to an anaphylactic reaction, or they end up in the hospital very ill. So, in most of our studies, patients come in and we have a cap in terms of the maximum amount you can tolerate, to be in the study, and in our studies. In the past, it’s been about 100 milligrams, so about a third of a peanut kernel, and the philosophy here is most accidental exposures can take place around 125 milligrams, so a lot of these patients would normally have an accidental exposure, whether it’s a cookie or something that is supposed to be nut-free, but it’s not. The philosophy of the product is to raise that level to 300, a 1000 and give some level of protection.”
“It’s not to have patients convert to oral intake of peanuts. And for most patients, really, that’s not their goal. The goal is just for the parents and caregivers to have peace of mind… ‘I’m providing my child with a therapy that will keep them safe, when I’m not with them, to protect them.’ So that’s the approach.”
Having hit a snag in 2020, where the company had to modify its patch for the four to 11-year-olds’ cohort, now, the company is working with the U.S. Food and Drug Administration (FDA) to have a regulatory path for Viaskin Peanut. As the REALISE phase 3 trials have just begun, and with safety studies ahead for two different indications, DBV Technologies expects to bring the product to commercial scale in the next few years, once it has been approved by the FDA.
PALFORZIA: an oral immunotherapy for food allergy to peanuts
Although the epicutaneous delivery of allergens is a novel idea that has been gaining ground lately, oral immunotherapies have been around for a while now. And in the fight against food allergens, it remains a revered mode of treatment.
One such company specializing in oral immunotherapies for food allergies is California-based Aimmune Therapeutics. Most advanced in its pipeline is the oral drug PALFORZIA, which is prescribed to mitigate allergic reactions to peanuts.
Peanut allergies are IgE mediated, where the allergen binds to IgE antibodies which activate immune cells (basophils and mast cells), causing an allergic reaction. This response occurs within minutes and up to two hours upon consuming the allergen. PALFORZIA can inactivate the immune cells which leads to a change in the antibody that enables protection from the allergen during continued intake of the therapy.
Approved by the FDA in 2020 – making it the first commercially-available peanut allergy treatment – and the European Commission (EC) the following year for patients aged between four and 17, the drug, like Viaskin Peanut, is designed to steadily expose the body to small amounts of allergen, while raising the dosage overtime, in order to desensitize patients to limited amounts of peanut protein.
Having halted trials for its oral immunotherapy for hen egg allergy in 2022, and despite a slump in sales for PALFORZIA – which was acquired by Swiss food and drink corporation Nestle in 2020 – the company currently aims to receive authorization for PALFORZIA to be given to peanut-allergic children aged one to three.
Vedanta’s investigational drug could reduce adverse side effects to oral immunotherapies
Meanwhile, based in the biotech hub of Cambridge, Massachusetts in the U.S. is Vedanta Biosciences, Inc., a company that has developed an oral drug for the treatment of peanut allergies. Presently in clinical trials, VE416 is being investigated as a monotherapy as well as in combination with an oral peanut immunotherapy.
The drug candidate comprises a bacterial consortium produced from bacterial cell banks. VE416 induced protective immune responses and reduced symptoms, observed in preclinical research. For its phase 1b/2 study which enrolled 40 people with peanut allergies, Vedanta will release topline data later this year. The study is examining whether the drug could reduce adverse effects in patients who are being administered other peanut immunotherapies.
While none of these therapies are cures for food allergies, as Mohideen expressed, the intent is to offer a certain level of protection from accidental exposure.
Mohideen, who believes that immunotherapy – and Viaskin in particular – could have a life-altering impact on the lives of people with food allergies, said: “As a company, we’re laser focused on getting peanut across the line. We’re working really diligently as we go to the different scientific meetings, and we speak to our investigators and key opinion leaders. There’s huge demand for additional therapies. And this is where we feel really compelled in our mission to get peanut and other treatments available to families and physicians because we know the unmet medical need is so huge.”