A lead study investigator highlights epicutaneous immunotherapy using DBV 712 (Viaskin Peanut; DBV Technologies), its study details, and breaks down its usability, indications, and treatment potential.
In this Contemporary Pediatrics Q+A interview,Matthew Greenhawt, MD, pediatric allergy and immunology specialist, Children’s Hospital Colorado, lead author, study investigator, EPOPEX and EPITOPE studies, breaks down DBV712 (Viaskin Peanut; DBV Technologies) and how it can play a role in peanut allergic toddlers aged 1 to 3 years old.
Can you explain the role of epicutaneous immunotherapy using peanut patch (DBV712) (Viaskin Peanut) for peanut allergic toddlers aged 1 to 3 years old? How is it used and how often?
Matthew Greenhawt, MD:
Presently, Viaskin Peanut is an experimental therapy still in development across all ages of investigation, including 1-to-3-[year-olds] and 4-to-7-year-olds. The EPITOPE phase 3 trial was just completed and published in [The New England Journal of Medicine} this May, and a safety study in the same patient population, COMFORT Toddlers, will initiate in Q1 2024. The VITESSE phase 3 trial in peanut allergic 4-to-7-year-olds is open for enrollment.
Viaskin Peanut is a daily therapy. It is a patch worn between the shoulders on the back, which allows for non-oral peanut desensitization, which many parents find highly appealing compared to orally ingested options for therapy. The patch contains 250 μg of peanut protein, or 1/1000th of a peanut kernel. A condensation chamber is formed between the allergen and the top layer of the skin, and, as natural water loss solubilizes the allergen, the immune system is exposed to the allergen (peanut protein).
Can you explain the process in which Viaskin Peanut was studied, what the primary and secondary outcomes were, and results?
Viaskin Peanut has been studied in 1–3-year-olds and 4–11-year-olds. EPITOPE evaluated toddlers 1–3 years and PEPITES was the original study for children 4–11 years. DBV has since launched a second Phase 3 pivotal study, called VITESSE, in children 4–7 years after evaluating the results of PEPITES and determining that greater response was seen in a younger peanut allergic population. VITESSE is currently enrolling subjects. Growing evidence from early introduction studies suggests that the allergic immune system is more modifiable early in life. Peanut allergy is commonly diagnosed very early in life, and only approximately 29% will naturally outgrow peanut allergy by age 6 [years].
EPITOPE compared toddlers 1–3 years randomized to 12 months of the investigational patch vs. toddlers 1–3 years randomized to 12 months of a placebo patch. All toddlers had to qualify for the study by reacting to 300 mg or less of peanut in a double-blind placebo-controlled food challenge at the study start. To be considered responders after 12 months, the most reactive toddlers at study start saw an increase in protection from having reactions triggered with 10 mg of peanut protein or less (1/30 of a single peanut kernel) to at least 300mg (a single large peanut kernel), and those who had reactions triggered with 30- 300 mg peanut to start had to increase their protection to at least 1000mg (a little more than 3 large peanut kernels, or 4-5 peanut M&M candies).
The primary safety endpoint was the number of adverse events during the use of the peanut patch or placebo. There were multiple secondary outcomes, including cumulative reactive dose, number of subjects reaching an eliciting dose of 1000 mg or greater, and change in eliciting dose, among others. Adverse events of special interest were defined as local (patch-site reactions, potentially leading to skin barrier disruption, or grade 4 reactions) or systemic (any acute systemic allergic reaction not associated with a food challenge, regardless of causal relationship to the peanut patch or placebo). EPITOPE was designed to have an open label extension (OLE) [of] up of 2 years, and to have a roll-over of the placebo group to receive a year of active treatment before rolling into the 2-year OLE.
In EPITOPE, after 12 months, there was a significantly higher rate of desensitization observed in the peanut patch group as compared to placebo (67% vs 33%). It should be noted that increased rates of adverse events were observed in the intervention group compared to the placebo group, which were mainly localized reactions at the patch site that diminished within the first three months of the study. Overall, only 1.4% of the intervention group vs no one in the placebo group had anaphylaxis related to the intervention, highlighting that desensitization was achieved with good safety. Overall, this is a highly reassuring safety signal, and a positive trial result in 1 – 3-year-olds.
DBV just announced 2-year results from the OLE study of EPITOPE. Viaskin Peanut showed improvement between months 12 and 24 of treatment with 81.3% of subjects reaching an eliciting dose of over 1,000 mg after 24 months of treatment. Almost 56% of subjects were able to consume a cumulative dose of 12 – 14 peanut kernels and more than 81% reached an eliciting dose of 3 – 4 peanut kernels. This is important because these are toddlers [who] started the study with an eliciting dose from fractions of a peanut kernel to about one whole peanut kernel. There were no treatment-related anaphylaxis or serious treatment adverse events in the second year of treatment. We also saw that 68% of those patients who were on placebo and crossed over to the OLE reached the EPITOPE responder definition—consistent with EPITOPE results.
Can you explain where in the FDA process Viaskin is, or if a BLA is planning to be submitted?
For Viaskin Peanut in 1–3-year-olds, the FDA has asked DBV to perform an additional study showing safety for a 6-month duration of wear, vs. placebo, to increase the number of subjects in the safety database to approximately 600. This safety study is called COMFORT Toddlers and will begin enrollment in Q1 2024. For Viaskin Peanut in the older age group, the company, in conjunction with direction from the FDA, reformulated the patch to adhere better, and, after post-hoc analysis showed a reassuringly stronger signal for efficacy and safety within the 4–7-year-old age bracket, initiated a Phase 3 trial called VITESSE for peanut allergic patients 4– 7 years of age, with a planned similar safety study to the 1– 3 year old age group (COMFORT Toddlers). The safety study in 4–7-year-olds will be called COMFORT Children. DBV is available to answer any specific regulatory questions that you may have.
When it comes to children younger than 4 years of age (Viaskin indication), what challenges are there for those with peanut allergies, and how can the primary health care professional play a role in the burden associated with the allergy for not only the child, but for the parent as well?
The primary concerns for children this age are that they are taught to avoid their allergen, and that they know to alert an adult if they have come in contact with that allergen and are developing symptoms. This needs to be done in a way to not frighten or adversely polarize the child to develop maladaptive coping and feelings towards food and peanut in particular. We don’t want them to be afraid of having to use epinephrine for treating a reaction, and do not want them to have inhibited socialization or excessive anxiety in social situations where peanut may be in the environment. Primary health care professionals are often the first visit when a caregiver suspects an allergy. They can partner to promptly refer these patients to an allergist for evaluation of the diagnosis and to determine what care plan is best suited for each patient’s needs, which will fit into the lifestyle of the family.
How could a potential approval change the treatment landscape in this indication?
This would be a non-oral, highly safe product that combines strong delivery of an immunologically potent signal in a safe fashion. More treatment options give patients more choice in a shared decision-making paradigm.
What adverse reactions were associated with treatment?
Across all ages, the primary adverse events were localized, generally mild, patch-adhesion site reactions that became less of an issue with more duration of wearing the patch. This resulted in site irritation and/or itching and were not considered serious. In the 1–3-year-old study, there were 4 cases of anaphylaxis, not all of them requiring epinephrine. One of these children discontinued therapy but the others resumed wearing their patch shortly after receiving treatment and had no further episodes. In the 4–11-year-old study, 10 episodes of anaphylaxis occurred in 8 patients, not all of whom received epinephrine. All episodes of anaphylaxis in both trials were mild to moderate and not life-threatening.