While for most people choosing a restaurant for dinner could be based on what they might be craving at the moment, for about one to five percent of the world’s population it is a well thought out decision that involves ensuring that there will be no cross contamination. on foods that are sure to trigger an allergy attack.
For Pharis Mohideen’s family, this has always been a concern. Mohideen, a father of two sons who is allergic to peanuts and tree nuts, recounts that even when applying to college, checking with the food staff to make sure that the canteen has a food allergy policy, it matters a lot where his kids go.
“If you can’t eat, you can’t go to college. So it sounds like an exaggeration, but if you have lived through it, the concern and worry and fear that parents and caregivers have about accidental exposure, it is huge,” said Mohideen, who, as chief medical officer (CMO) of DBV global Technologies biopharma, working to develop immunotherapies to treat food allergies.
As part of DBV’s mission to advance epicutaneous immunotherapy, its new platform Viaskin aims to deliver drugs through the skin to target food allergies, particularly peanuts.
“So the concept here is that we use the skin as a conduit for introducing allergens into the body, not by oral intake or injection. And the way the technology works is very ingenious,” said Mohideen.
DBV immunotherapy for food allergy to peanuts
The technology, which is an epicutaneous immunotherapy patch, consists of a quarter-sized ring of foam – about 2 millimeters wide and thick – into which 250 micrograms of the allergen, which is about 1/1000 of a pea kernel, is electro-sprayed. With a plastic layer like a band-aid over a ring attached to the individual’s back, the peanut protein doesn’t come into direct contact with the skin. Conversely, because the body loses water naturally, 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 they can detect foreign molecules and activate immune cells – and carry the allergen to the lymph nodes. On arrival at the lymph nodes, specific T cells are activated and trigger an allergic response, desensitizing the patient to the peanut protein.
“There’s two concepts going on here: In animal models, we don’t have systemic exposure to the protein because it’s very small, very small amount, and it’s taken up by these antigen-presenting cells. And it does two things, it still allows the immune response to happen, but at a much safer level, because you’re taking small amounts of pea protein exposure every day. So, over three years of therapy, you are exposed to a total of one bean – one bean is about 250 to 300 micrograms… The mechanism is unlike anything on the market today,” said Mohideen, whose company is also working to combat intolerance to cow’s milk as well as eggs – both are common food allergies – using the Viaskin platform.
With a focus on therapeutic measures for children, the food allergy immunotherapy company is developing its line after a placebo-controlled phase 3 EPITOPE clinical trial for children aged one to three years with peanut allergy reaped positive results. Along with the toddler study, trials were conducted for different age groups, with the REALIZE study for children aged four to 11 years and separate trials for adolescents and adults, where patch sizes differed in each category.
Can the Viaskin platform target multiple food allergies?
Meanwhile, DBV Technologies has also completed a phase 1/2 study for their immunotherapy to treat food allergy to dairy, and phase 2 is scheduled for next year. After proving its success in a proof of concept study for eosinophilic esophagitis (EoE) – an allergic condition that targets the esophagus – several years ago, milk patches were expected to achieve promising results.
Leveraging the mechanisms behind the platform can help address multiple indications, according to Mohideen. “The beauty of this product is that we can take the exact same patch, use it for a cow’s milk allergy, then use it for something else like EoE. And then on our channel, you can imagine, we can put anything you want on the product. So cashew, sesame, all the other food allergens definitely play a role, down the road. Obviously, we want to focus and get the nuts over the line first, and then we’ll slowly build up some of the other indications.
While clinical trials have established Viaskin’s safety, Mohideen explains that one of the most common side effects with patches is the occurrence of local application site reactions. Since many of the target patients suffer from eczema and asthma, and have sensitive immune systems as a result, the therapy causes reactions in the patches. With a low rate of anaphylactic reactions, Mohideen states that side effects are usually treated with epinephrine injections.
Although the therapy, which is to be administered over a period of about three to five years – the longer the duration, the stronger the response – is capable of increasing protection from small intakes of allergens, it is, however, not a drug. Mohideen describes it as an air bag in the car, a sort of safety net in the event of an accident, or in this case, when accidental exposure to allergens occurs.
Mohideen said: “What we are trying to do is increase the amount of peanut protein that patients can tolerate. So they don’t have an accidental exposure that causes an anaphylactic reaction, or they end up in the hospital seriously ill. So, in most of our studies, patients come in and we have limits in terms of the maximum amount that you can tolerate, to be in the study, and in our study. In the past, it was about 100 milligrams, so about a third of the kernel of a bean, and the philosophy here is most accidental exposures can occur at around 125 milligrams, so many of these patients are usually going to have an accidental exposure, whether it’s a cookie or something that should be nut-free, but it isn’t. The philosophy of this product is to take that level to 300, to 1000 and provide multiple levels of protection.”
“This is not to make patients switch to oral intake of peanuts. And for most patients, really, that’s not their goal. The goal is simply for parents and caregivers to have peace of mind… ‘I give my children therapy that will keep them safe, when I’m not with them, to protect them.’ So that’s the approach.”
After hitting a roadblock in 2020, where the company had to modify its patch for the age group of four to 11 years, now, the company is working with the US Food and Drug Administration (FDA) to have a regulatory pathway for Viaskin Peanut. Because phase 3 trials of REALIZE have just started, and with safety studies ahead for two different indications, DBV Technologies hopes to bring the product to commercial scale within the next few years, once approved by the FDA.
PALFORZIA: oral immunotherapy for food allergy to peanuts
Although epicutaneous allergen delivery is a new idea that has been gaining ground recently, oral immunotherapy has been around for a while now. And in the fight against food allergens, it remains a respected remedy.
One company that specializes in oral immunotherapy for food allergies is California-based Aimmune Therapeutics. Most advanced in its line is the oral drug PALFORZIA, which is prescribed to reduce allergic reactions to peanuts.
Peanut allergy is IgE mediated, in which the allergen binds to IgE antibodies that activate immune cells (basophils and mast cells), causing an allergic reaction. This response occurs within minutes to two hours after consuming the allergen. PALFORZIA can inactivate immune cells leading to changes in antibodies that allow protection from allergens during continuous therapeutic intake.
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 between the ages of four and 17, the drug, like Viaskin Peanut, is designed to stably expose the body. to a small amount of allergen, while increasing the dose over time, to desensitize the patient to limited amounts of pea protein.
After concluding trials of oral immunotherapy for chicken egg allergy in 2022, and despite declining sales for PALFORZIA – which was acquired by Swiss food and beverage company Nestle in 2020 – the company is currently aiming to receive authorization for PALFORZIA to be administered to peanut-allergy. children aged one to three years.
The investigational drug Vedanta can reduce the adverse side effects of oral immunotherapy
Meanwhile, based in biotech hub Cambridge, Massachusetts in the US is Vedanta Biosciences, Inc., a company that has developed an oral medication for the treatment of peanut allergies. Currently in clinical trials, VE416 is being investigated as monotherapy as well as in combination with oral peanut immunotherapy.
The drug candidates consist of a consortium of bacteria generated from a bacterial cell bank. VE416 induces a protective immune response and reduces symptoms, observed in preclinical studies. For a phase 1b/2 study involving 40 people with peanut allergies, Vedanta will release topline data later this year. This study examined whether the drug could reduce side effects in patients given other peanut immunotherapy.
While neither of these therapies cure food allergies, as Mohideen points out, their goal is to offer some degree of protection from accidental exposure.
Mohideen, who believes that immunotherapy – and especially Viaskin – can have a life-changing impact on the lives of people with food allergies, said: “As a company, we focus on lasers to deliver peanuts. We work very diligently when we go to different scientific meetings, and we talk to our main investigators and opinion leaders. There is a great demand for adjunctive therapy. And this is where we feel very empowered in our mission to get peanuts and other treatments available to families and doctors because we know the unmet medical need is huge.”