Disclosures: Dombkowski reports serving as the CEO of Alladapt Immunotherapeutics. McClintock reports serving as the chief medical officer of the company.
Oral immunotherapy has shown promise in inducing remission of specific food allergies, with one FDA-approved option available for peanut allergy, but these patients often shoulder the burden of multiple food allergies.
Alladapt Immunotherapeutics has completed patient enrollment in its Harmony phase 1/phase 2 study of ADP101, an oral immunotherapy designed for treating multiple food allergies.
The double-blind, placebo-controlled study will evaluate ADP101’s use in 73 adults and children who will be assessed at 15 sites in the United States. Nearly two-thirds of these patients have demonstrated allergy to more than one of the 15 allergens that ADP101 targets.
Healio spoke with Alladapt chief medical officer Dana McClintock, MD, and cofounder and CEO Ashley Dombkowski, PhD, to find out more about the therapy and the study.
Healio: What is the current standard of care for treating IgE-mediated food allergies?
McClintock: The standard of care across food allergy is avoidance of the food and treatment of the reactions that occur. Unfortunately, even when you’re trying your best to avoid these foods, accidental exposure occurs. That’s why patients carry an EpiPen.
The one FDA-approved therapy for treating IgE-mediated food allergies at this point is Palforzia (Peanut [Arachis hypogaea] Allergen Powder-dnfp, Aimmune Therapeutics), which is specific to pediatric patients who have peanut allergy. That’s the only one, unfortunately, that directly treats the disease beyond avoidance and treating reactions.
Healio: How does ADP101 aim to improve treatment?
McClintock: ADP101 is a broader oral immunotherapy. Instead of being focused just on peanuts, it also will target almond, hazelnut, cashew, pistachio, pecan, walnut, milk, egg, cod, salmon, shrimp, wheat, soy and sesame. The therapy includes the ability to desensitize across the major causes of food allergy reactions — things that, unfortunately, can result in severe reactions and trips to the ED when patients have accidental exposures. It builds on that early, important work that Palforzia has done, but it’s also able to potentially help a wider range of patients who have food allergy.
Dombkowski: Whether you’re a child or an adult with an allergy, lifetime ED use is 40% to 60%. All foods have a significant risk for sending people to the ED.
Ashley Dombkowski, PhD
Also, food allergy is increasingly a multi-allergic disease, as research continues to show. More than half of children with peanut allergies are multi-allergic. Two-thirds of adults with egg allergies are multi-allergic. So, with a disease that is increasingly broad in terms of potential triggers, and increasingly deep in terms of burden of disease, it really sets up the need for an approach that could be broadly applicable.
Our approach is to take oral immunotherapy and have a single, standardized, industrialized, FDA-approved, eventually reimbursed drug that is premeasured, precise and dosed for patients whether they have mono- or multi-allergy through a very broad range of triggering foods.
Food allergy is on the rise globally, yet I have rarely seen such a huge unmet medical need neglected by the biopharmaceutical industry for so long. We see food allergy as the last frontier of atopic disease. We’re excited to see pharmaceutical companies increasingly coming around to food allergy because we think patients need options and FDA-approved, validated, scientifically driven interventions that have been missing for so long.
Healio: Can you tell us about the mechanics of how a single drug can target multiple allergens?
Dombkowski: We start with raw materials that come out of the industrial food supply chain, and we put them through a manufacturing process to make them pharmaceutical-grade as per FDA. We have six tree nuts, two fin fish, a pink fish and a white fish — salmon and cod — and shrimp, soy, wheat, milk, egg, sesame, and peanut. We combine those in a very precise ratio so they are equal parts by protein weight. We also go through volume reduction to remove certain fats and in other cases carbohydrates, etc. and minimize doses. Patients can go through a two-and-a-half to three log increase in their exposure, starting at sub-milligram doses, and then increasing over time. We’re implementing a low and slow up-dosing protocol.
We spent a lot of time talking with patients, families, caregivers and clinicians about what their needs are and what they’re looking for, and we’ve incorporated that feedback. We also will continue to be on listening tours as we continue our development, and that’s included in the design of our Harmony study.
McClintock: We wanted to have the most common causes of food allergy together so we could enroll and evaluate a broad range of patients. It builds on that foundation and allows for scale for truly global products that could bring this type of therapy to a larger number of patients around the world using a very standardized and pharmaceutically approved approach.
Healio: So, the approach is designed to accommodate multiple proteins?
Dombkowski: We understand that oral immunotherapy appears to work by modulating that IgE4-to-IgE ratio. When you’re using the gut via oral immunotherapy to retrain the immune system, whether it’s a single protein or a mixture of proteins, once it goes into a patient and goes through digestion and is broken down, it’s really about the individual proteins that are taken up and seen by the immune system. So why should it just be one? A protein is a protein is a protein. Why couldn’t it be more than one, as long as you get the proteins right and make sure your dosing protocol is gentle enough? It should be able to be done simultaneously.
Healio: What can you tells us about the Harmony study?
McClintock: Patients qualify for the study based on a clinical history of food allergy that we confirm at entry using a double-blind placebo-controlled food challenge, which is the gold standard. We confirm that they are reactive to their food. Of the foods we’re looking to treat, they must react at the 100 mg level and below to at least one and no more than five. So, they are quite sensitive.
Then, they’re randomly assigned to either one of two active dose arms to achieve dose levels for maintenance or matched placebo. They go through up-dosing steps, starting very low and gradually increasing every couple of weeks until they reach a plateau level. We also have a lower dose and a higher dose plateau. We’re testing two levels, and we’ve built in flexibility to allow for patients to plateau early if needed. The goal is really to be able to help them get to that higher maintenance level over time, so we give them time to do that.
After a period of up-dosing and the maintenance level, we do an exit food challenge, where we repeat the test from the starting point. We look at how many patients can increase their threshold and how high their reactivity level is.
Many different studies have shown oral immunotherapy’s ability to raise that threshold on food challenge. That’s what we’ll be evaluating. We’re looking at our treatment vs. a matched placebo to see what percentage of patients will be able to successfully raise that threshold by the end of the study.
Healio: Was it difficult finding patients for the study?
Dombkowski: We recruited patients aged 4 to 55 years. Despite the complexities of COVID-19, we had huge demand. The demand from patients exceeded our expectations, which I think speaks to the pent-up demand and interest among this population.
Healio: What is the timetable for treatment during the study?
McClintock: Somewhere between 4 and 6 months to do the up-dosing, depending on the patient’s needs. Then another couple of months, depending on how long that first part takes to get to the exit procedure.
Healio: When do you expect to present the results?
McClintock: We’re looking at approximately a year from now because we have that up-dosing timeframe. Then we have a maintenance period of a few months. We also need to conduct those exit challenge procedures and get the data entered and analyzed.
Healio: What would the next step be after that?
Dombkowski: We’re contemplating a very robust clinical program. Obviously, we want to move ahead with phase 3 clinical development, and we’re also interested in additional ways we can think about expanded patient populations and combinations with other drugs. We really want our holistic, global, pediatric and adult population to be in our sights, and we think this program deserves to be brought to as many patients as possible.
Healio: If the study is successful, what impact will it have on patients?
Dombkowski: We are very sensitive to the feedback. We continue to see patients who are meticulous and constant in their chronic avoidance of allergens, particularly multi-allergen patients and patients who don’t have peanut allergies. Avoidance is such a burdensome endeavor. We’re committed to working with resourcing and very responsibly developing a new intervention. Our entire team goes to bed thinking about our patients, and we wake up thinking about them. We’re really all in here.
McClintock: People who don’t experience food allergies often underappreciate just how challenging it is for those who do. We’re excited to be bringing potential options to these patients who live with a lot of anxiety about what they eat, particularly when you have multiple allergies or allergies outside of peanut, which aren’t as appreciated but can be just as severe and problematic. The big focus for us is to address this unmet need, and we’re excited to be part of bringing it to the fore.