Children and adults with peanut allergy can suffer life-threatening consequences if exposed to even minute traces of peanuts. But a clinical trial of an oral immunotherapy drug, published in November 2018 in the New England Journal of Medicine, provides significant hope that such events might soon be preventable.
The study included almost 500 children from ages 4 to 17, all with known peanut allergy. Of those, 372 were given tiny amounts of peanut protein in the form of a pharmaceutical called AR101, while 124 received a placebo.
In the treatment arm, the dose of peanut protein was gradually increased over six months, and then kept at a maintenance level for another six months. By the end of the study, two-thirds of those participants could ingest at least 600 milligrams of peanut protein (the amount in about two peanuts) without experiencing an allergic response, compared to just 4 percent of those in the control group.
Five of the study’s 71 authors are affiliated with Aimmune Therapeutics, the company that created the drug and sponsored the clinical trial. Daniel Adelman, MD, the corresponding senior author and the company’s chief medical officer, is an allergist and immunologist at UC San Francisco who has more than two decades of experience in biotechnology and drug development. Dr. Adelman is also a UC alumnus: He received a bachelor’s degree in biology from UC Berkeley and his medical degree from UC Davis.
We spoke with Dr. Adelman about AR101, which has been submitted to the FDA for approval. [Update: The FDA approved the drug Jan. 31, 2020, under the brand name Palforzia. Read the FDA's announcement here.]
BW: How did this effort start?
Adelman: It’s been known for decades that immunotherapy could be used to desensitize people to peanut allergies. In fact, the first reported case of oral desensitization was in 1908 for egg allergy.There have been people who have been using what we call “home-brew” and trying to do this themselves, but none of the products have been characterized and controlled for allergen content.
Back in 2011, a patient advocacy organization held a research summit that included academic food allergy experts, allergists from the NIH, representatives from the FDA, and people from industry to address the problem and try to come up with a solution. It was felt that oral immunotherapy was the best potential solution and peanut allergy should be the first food allergy targeted because it has the highest prevalence in the United States and Europe.
Then the question was how to get a product characterized and developed appropriately so that it could be approved by the FDA. From that research summit, the Allergen Research Corporation was founded with seed money coming from some of the advocates and organizations to figure out how to solve the problem of producing a consistent, allergen-characterized, and reproducible peanut product that could be used for oral immunotherapy. We wanted to develop a product that would serve any peanut-allergic patient. We have turned a food into a medicine by imposing the appropriate pharmaceutical standards for development of a medicinal product, and what we have now is a highly characterized biologic drug.
Why is the focus on peanut allergies rather than other nut allergies?
Peanut protein is hard to avoid. It’s an inexpensive form of high-quality protein and it’s used in a lot of different things, without necessarily being included on the package labels. You don’t necessarily know that your curry has peanut protein. Pretzels, ice cream—it’s hidden in a lot of foods, and it’s very difficult to avoid it completely. Walnuts, cashews, and hazelnuts are also allergenic, but they are easier to avoid.
Most children who are peanut allergic become sensitized sometime in the first or second year of life. Once allergy to peanuts develops, only about 20 percent of those children ever resolve their peanut allergy. In general, if you’re still peanut allergic by age 4 or 5, you’re likely going to be allergic for life.
Peanut and other allergies are known to be increasing in prevalence. Why is this?
There are a lot of things we don’t know for certain, but theories include the so-called hygiene hypothesis—that we’re not exposed to enough dirt and pathogens as children, so we end up directing our immune responses to things that are otherwise innocuous. Asthma, other allergic diseases, and autoimmune disorders have all been increasing over the past three to four decades.
Another idea is that our diets have included a lot less roughage and natural fibers and a lot more meats and refined grains and sugars, which has altered our gut microbiome. That might very well affect the way we process antigens, including peanut antigens.
Can you describe the desensitization process used in the study?
We start off at very small quantities of peanut protein (equivalent to 1/600thof a peanut) and do a slow dose escalation to get to a maintenance dose of 300 milligrams of peanut protein, or the equivalent of about 1 peanut kernel. The desensitization process to get to the maintenance dose takes about six months, and then they stay on that maintenance dose indefinitely.
Our study was conducted over a one-year period—that is, six months of up-dosing and six months of maintenance therapy. At baseline, participants in the study would experience an allergic reaction if exposed to just 10 milligrams of peanut protein—that’s around 1/30th of a peanut. The median tolerated dose level at the end of study was 1,000 milligrams of peanut protein, or a 100-fold increase in the ability to tolerate exposure without having an allergic reaction. That’s the equivalent of three to four peanuts.
But the goal is not a cure, right?
Curing food allergies is the ultimate goal, but is not possible at this time. Therefore, our current goal is not cure, but rather to protect people from potential life-threatening allergic reactions from accidental exposure to peanuts.
Most peanut allergic kids don’t want to eat peanuts or peanut butter anyway. They’ve got real peanut aversion, they don’t like the smell, the taste—they have been conditioned to avoid peanuts. The problem is that these kids are often socially isolated in addition to the allergy danger. They’re often not invited to the birthday parties because parents don’t want to take on the liability of hosting a peanut-allergic kid. It’s got a lot of big emotional impacts. Our goal is to protect people from those potentially life-threatening allergic reactions and to free them up psychologically and socially.
What happens now?
In December, we submitted our license application to the FDA for approval, and sometime in the middle of 2019 we will be submitting a similar application to the European regulatory authorities for licensing in Europe. We have both Breakthrough Therapy status and Fast Track designation with the FDA because peanut allergy is recognized as a serious unmet medical need. In addition, we expect to have priority review, so we should have an answer by the fall of 2019. So it’s possible the drug could be commercially available by this time next year.
This opinion does not necessarily reflect the views of the UC Berkeley School of Public Health or of the editorial board at BerkeleyWellness.com.
Also see Food Allergy or Intolerance?
Originally published January 17, 2019. Updated February 3, 2020.