Laird Harrison

March 09, 2017

ATLANTA — Children became progressively less sensitive to peanuts during a 3-year trial of immunotherapy delivered through a skin patch. There were few adverse effects from the patch, and the children were comfortable with wearing it.

"This is something we believe will provide protection," said study investigator Hugh Sampson, MD, from Mount Sinai Medical Center in New York City, who is chief scientific officer of DBV, the maker of the Viaskin skin patch.

Dr Sampson presented results for children 6 to 11 years of age from the phase 2b OLFUS open-label extension phase of the VIPES study during a news conference here at the American Academy of Allergy, Asthma and Immunology Meeting.

Peanut allergies are becoming increasingly common. Both oral and sublingual immunotherapies, in which small amounts of peanut are gradually introduced, have shown promising results. However, children are sometimes afraid to eat even these small doses, and adverse effects are common. In fact, the US Food and Drug Administration has not approved any immunotherapy for peanut allergy.

The skin patch, the size of a round Band-Aid, acts as a condensation chamber, applying small amounts of peanut to the skin. Every day a new patch is adhered to a different area of the body.

Natural water loss from the skin dissolves and releases the peanut protein, which penetrates the stratum corneum. It is believed that Langerhans cells then transport the peanut protein to lymph nodes, where regulatory T-cells are activated.

VIPES Study

In the VIPES study (NCT01675882), Dr Sampson and his colleagues assessed 221 people 6 to 55 years of age with a peanut-specific immunoglobulin (Ig)E level above 0.7 kUA/L, a wheal diameter on a skin-prick test of at least 8 mm, and an allergic reaction to 300 mg of peanut protein or less. Participants received peanut doses of 50 µg, 100 µg, or 250 µg, or placebo for 12 months. Responders were defined as people who could eat at least 1000 mg of peanut protein without a reaction, or people who had at least a tenfold increase over baseline in the eliciting dose of peanut protein.

Results were best with the 250 μg dose, so all study participants, including those in the placebo group, were invited to join the OLFUS extension (NCT01955109) and continue on that dose for another 24 months; 171 adults and children enrolled.

At the end of the extension period, after 36 months of treatment with the skin patch, 15 of the 18 children (83.3%) met the definition of responder.

"I think that's pretty good," said Dr Sampson.

This was an increase over the 53.3% rate of responders at 12 months. And the median cumulative reactive dose increased from 444 mg at 12 months to 1440 mg at 36 months.

Over the 36 months, the median level of peanut-specific IgE dropped by 36.5% in the children, and peanut-specific IgG4 increased by 473%. "These are typical changes we see with most forms of immunotherapy," Dr Sampson explained.

There were no treatment-related serious adverse events and no treatment-related epinephrine use. All participants experienced some adverse events — most frequently erythema, pruritus, eczema, swelling papules, dermatitis, and urticaria — but these were easily managed with antihistamines and topical steroids. And the severity and frequency of these events decreased with time, the researchers report.

"We're very pleased with the outcome with the 250 patch in this age group, and that's why we're driving forward with the phase 3 trial," Dr Sampson said.

His team has now enrolled 350 children in the phase 3 trial and is launching an additional safety trial.

Adolescents and adults were less responsive to the patch. "That's not to say that there might not be efforts to optimize it for the adult population," he pointed out.

One reason the results might be better in children is that Langerhans cells tend to congregate around hair follicles, Dr Sampson explained. The number of hair follicles does not increase as children grow, and as a result, they spread out. Consequently, a skin patch is likely to interact with more Langerhans cells in children than in adults.

These findings are encouraging, but it is too early to tell whether one type of oral immunotherapy will emerge as being better than the others, said Edwin Kim, MD, from the University of North Carolina at Chapel Hill.

"My true clinician belief is that there is a right treatment for each patient," he told Medscape Medical News. So far, oral immunotherapy appears to have stronger effects but also causes more adverse events than the skin patch or sublingual administration, he pointed out.

Oral Immunotherapy

"There are some patients who are going to want the therapy that's been around the longest: oral immunotherapy," he said. "But there are going to be some for whom it's all about ease of administration."

Dr Kim presented findings from a study of sublingual drops during the news conference.

In their study, he and his colleagues administered sublingual drops containing 2 mg of peanut to children 1 to 11 years of age with peanut allergy.

The 37 children who were considered desensitized after 12 months continued for 36 to 60 months. At that point, 12 of the children (32%) were able to eat 5000 mg of peanut protein without reacting. The median successfully consumed dose of peanut was 1750 mg.

 
One thing we've discovered is that the vast majority of these patients don't want to eat peanut.
 

When these 12 children stopped taking the sublingual drops for 2 to 4 weeks, 10 achieved sustained unresponsiveness and were able to eat 5000 mg without reacting. The other two were able to eat up to 3750 mg before reacting.

It's not clear how long patients can remain desensitized to peanut, said Dr Kim, or how much desensitization is enough.

But the true goal of immunotherapy is being debated in the research community.

"One thing we've discovered is that the vast majority of these patients don't want to eat peanut," he reported. Instead, they want to avoid a reaction if they accidentally consume peanuts.

"What we're talking about is protection. These patients want to be assured that, in their lives and in their social situations, they're not going to have a reaction."

The VIPES-OLFUS study was funded by DBV Technologies, the maker of the patch. Dr Sampson reports financial relationships with UCB, FARE, ITN, Thermo Fisher Scientific, and UpToDate. Dr Kim reports financial relationships with Aimmune Therapeutics, FARE, the Benaroya Research Institute, the Consortium of Food Allergy Research (CoFAR), and the former NCCAM (now the National Center for Complementary and Integrative Health.

American Academy of Allergy, Asthma and Immunology Meeting (AAAAI): Abstracts L8 and 559. Presented March 5, 2017.

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