Q&A: DBV Technologies announces progress on Viaskin Peanut patch

Key takeaways:

• The Viaskin patch offers epicutaneous immunotherapy with a 90% compliance rate.
• 67% of patients treated with Viaskin Peanut 250 µg were considered responders, with a significant increase in peanut tolerance.

DBV Technologies recently provided updates on its Viaskin Peanut Program for children and toddlers, announcing recruitment for the VITESSE study and progress in the COMFORT Toddlers supplemental safety study.

According to a recent earnings release, the VITESSE phase 3 study for children aged 4 to 7 years with peanut allergies is expected to finish its recruitment process by the end of quarter three of this year. The COMFORT Toddlers supplemental safety study for children aged 1 to 3 years with a peanut allergy is undergoing dialogue with the FDA.

To learn more about the Viaskin Peanut Patch and what these studies entail, Healio spoke with Pharis Mohideen, MD, chief medical officer at DBV Technologies.

Healio: What are the current immunotherapy treatments for peanut allergy?

Mohideen: There are currently two FDA-approved immunotherapy treatments for peanut allergy.

Palforzia (Peanut [Arachis hypogaea] allergen powder-dnfp, Stallergenes Greer) is a form of oral immunotherapy. OIT exposes the patient to increasing amounts of a food allergen in a stepwise manner. In this case, peanut powder is mixed with food once per day to slowly build up to a maintenance dose of about one peanut kernel, or 250 mg to 300 mg of peanut. This slow, incremental daily exposure allows the immune system to adapt and generally not react to the allergen or to react less severely. Typically, biweekly increases in the peanut protein dose are done in the allergist’s office, and it usually takes approximately 4 to 6 months to escalate to the maintenance dose. OIT was first reported over 100 years ago and has been used in various forms for many kinds of food allergies, but Palforzia’s approval in 2020 was the first time the FDA approved OIT.

The other therapy is omalizumab (Xolair; Genentech, Novartis), which is a monoclonal antibody that binds to IgE, an immunoglobulin made by the immune system. IgE antibodies attach to mast cells and basophils, and when an allergen (eg, peanut) enters the body and comes in contact with these cells, IgE activates these cells to release chemicals that cause allergic reactions. Omalizumab blocks the IgE antibody from attaching to mast cells and basophils, and therefore prevents these cells from triggering an allergic reaction. It is given as an injection once or twice a month.

These are the only FDA-approved therapies for treating food allergies, each with potential drawbacks related to possible side effects or mode of delivery, and so it is critically important that companies continue to pursue other treatment options in order to provide multiple options for patients and families.

Healio: How does the Viaskin Peanut patch work?

Mohideen: The Viaskin patch is designed in a completely different way than OIT or omalizumab. This is a novel technology utilizing a small condensation chamber and is a form of epicutaneous immunotherapy, or EPIT. It uses the skin as the conduit to deliver a very small amount of peanut protein, only 1/1,000th of a peanut kernel or 250 µg, to the patient. A patch is applied to the mid-back area on a daily basis, and no increase in the dose is required. Natural water loss from the skin accumulates in the condensation chamber, solubilizing the peanut powder attached to the inner patch chamber, which then comes in contact with the skin. Due to the occlusive property of the patch, the peanut protein enters the uppermost layer of the skin, where it is taken up by specialized immune cells (Langerhans cells, or LCs) that then carry the peanut protein via the lymphatic system to regional lymph nodes. Peanut protein does not enter the systemic (blood) circulation, thus reducing the chance of activating an allergic reaction. In the regional lymph nodes, the LCs present the peanut protein to other cells (T cells) that can downregulate the allergic response (T regulatory cells) and activate protective antibody-producing cells (T helper cells). These various types of T cells then travel to other parts of the body and reside in the skin, gut and respiratory tract to downregulate/block allergic reactions.

We have learned a great deal about the potency of the skin to induce desensitization through our extensive preclinical research studies, and we continue to investigate the exact mechanism by which desensitization with the Viaskin patch occurs. What we find quite amazing from observations in our clinical trials is that over the course of 3 years of treatment, the study participants are only exposed to a total of about one peanut kernel. We believe that there is a large multiplier effect by using the skin as a conduit compared with the gastrointestinal tract.

It is important to note that the Viaskin patch is an investigational product that has not yet been approved by the FDA or any other regulatory agency.

Healio: How does it improve upon these other immunotherapies?

Mohideen: I am not sure “improve” is the best way to describe it. We believe that Viaskin Peanut offers a very different experience for the patient as well as the parent or caregiver. One of the biggest differences with Viaskin Peanut is that it is designed to be convenient and simple to use. Our clinical studies have been conducted with no restrictions on activities or alterations during respiratory illnesses while the patch is worn. By introducing tiny amounts of peanut protein via the skin, there is less chance of peanut protein entering the circulation, where it can come in contact with mast cells and basophils and activate an allergic reaction. In addition, we have been told that there is also a very positive emotional experience that can take place when a parent or caregiver puts the patch onto the child, physically touching the skin, and applying the treatment. There can be a strong connection where the parent or caregiver can physically and emotionally feel that “Today, I’m doing as much as I can to ensure my child’s safety against accidental exposure” as they apply the patch. It can be very powerful.

Based on peer-reviewed data, OIT typically has certain restrictions related to usual activities of daily living to try to reduce the risk for anaphylactic reactions taking place after consuming the peanut powder. With Viaskin Peanut, clinical trials have been designed with no restrictions on daily activities, and participants have demonstrated very high compliance rates, which we believe reflects Viaskin’s ease of use. The EPIT mechanism of action and the very small amount of peanut protein also appear to play a central role in the safety profile. The tolerability of Viaskin Peanut has been very good in our clinical trials.

The efficacy data of the three treatment approaches are not easy to compare because the studies were designed differently with different endpoints, but over the long-term, I would say the published clinical study results of all three show comparable efficacy data, so a lot of it may come down to what fits a family’s lifestyle and the safety profile. Having several treatment options is always a good thing for patients and their caregivers, and we believe that more options are needed for treating all food allergies.

Healio: Could you summarize the efficacy and safety results of your studies so far?

Mohideen: In our 12-month study in 1- to 3-year-olds with peanut allergy, 67% of participants treated with Viaskin Peanut 250 µg were considered responders compared with 33.5% for placebo. Being a responder meant that the amount of peanut protein a participant consumed before having an allergic reaction increased by a clinically meaningful level at the end of 12 months of treatment.

Another way to present this is in terms of milligrams of peanut protein. At the start of the study, in the active treatment arm, the median amount of peanut protein that caused an allergic reaction, known as the eliciting dose, was 100 mg. At the end of 12 months of treatment, 65% of participants treated with Viaskin Peanut increased their eliciting dose to 1,000 mg (about three to four peanut kernels) or more. After an additional year of treatment, 2 years in total, this increased to 81% of participants. Additionally, 56% of participants could consume 3,444 mg (10 to 12 peanut kernels) without having an allergic reaction. In terms of accidental peanut consumption amounts, those changes provide a tremendous amount of protection.

In clinical trials, Viaskin Peanut has been very well tolerated. Compliance rates are above 90% in our studies, even over multiple years of treatment. The most common safety event observed has been local skin reactions at the site where the patch is placed. This occurs often, but usually tends to subside over time and rarely leads to stopping treatment with the patch. The rates of Viaskin Peanut-related (ie, assessed by study investigators as being possibly or probably related) anaphylactic events in the 1- to 3-year-old study have been very low (1.6% during the first year and 0% during a second year of treatment), and no participants have reported any severe systemic medical issues related to treatment.

Healio: Could you provide an update and details about the VITESSE study of children aged 4 to 7 years and the COMFORT study for toddlers?

Mohideen: The VITESSE study in 4- to 7-year-olds with peanut allergy uses a modified Viaskin Peanut patch. The main differences between the modified patch and the original patch used in the 1- to 3-year-olds studies are that the modified patch is round in shape and slightly larger. The 250 µg dose remains unchanged, as does the foam ring surrounding the condensation chamber.

Our clinical trial sites and families have done an awesome job, and we expect to close recruitment very soon. As far as I know, this is by far the largest clinical trial ever conducted in this age group for any food allergy treatment.

We are working closely with the FDA to finalize the protocol for the COMFORT Toddler supplemental safety study in 1- to 3-year-olds. I am confident we can get to a final protocol soon and initiate this important study.

Healio: What other studies are in the works?

Mohideen: We have been focused on getting Viaskin Peanut approved, and I believe we are on a good path. But remember, we also have two other indications with phase 2 data. We completed a phase 2a study (MILES) in participants allergic to cow’s milk protein. The results of that study have been published. We are looking to do a follow-up study in the near future. We also had a single center, phase 2 trial treating eosinophilic esophagitis with our Viaskin Milk patch. This study was completed and the results published by Jonathan Spergel, MD, PhD, and his colleagues at Children’s Hospital of Philadelphia. I’m really excited to move those indications forward in the near future.

Healio: Where is Viaskin on the path to FDA approval?

Mohideen: We have two separate biologics license applications that we can file, one with the original, square patch in toddlers aged 1 to 3 years and the second with the modified, round patch in children aged 4 to 7 years, both for treatment of peanut allergy. This provides a lot of regulatory flexibility.

For the toddler indication, we have already completed the 12-month efficacy and safety study, called EPITOPE. The results of this study were published in The New England Journal of Medicine in 2023. We are currently engaged with the FDA in ongoing dialogue on the supplemental safety study in 1- to 3-year-olds with peanut allergy. The indication in children aged 4 to 7 years will need to wait until VITESSE is completed and we analyze the data. We estimate that the topline results will follow approximately 12 months after the last patient is screened, which we anticipate will occur by the end of the third quarter of 2024. So, we feel we are in a good place as far as pursuing FDA approval for both age groups in the near future.

Healio: Do you have anything else you would like to add?

Mohideen: First, I would like to thank our investigators and their dedicated staff. Doing clinical studies is getting harder and harder for so many reasons. They work so hard and are so good at what they do. We are very appreciative. Secondly, I want to thank the families that participate in our studies. It takes a very special family to give so much time, energy and emotion to participate. It is not at all easy and it is a major commitment. Without both of these groups, we really cannot make any progress in the treatment of food allergies, and so I want to give my deepest thanks.

Reference:

• DBV Technologies provides updates on the Viaskin Peanut program in children and toddlers and reports second quarter and half-year 2024 financial results. https://dbv-technologies.com/press_releases/dbv-technologies-provides-updates-on-the-viaskin-peanut-program-in-children-and-toddlers-and-reports-second-quarter-and-half-year-2024-financial-results. Published July 30, 2024. Accessed July 30, 2024.