Largest-ever clinical trial for peanut allergy advances pediatric treatment closer to FDA approval

The University of South Florida was one of two Florida sites that tested the new immune therapy drug manufactured in Clearwater.

Dr. Thomas Casale, principal investigator for the USF Health arm of the large-scale study testing a new drug for severely peanut-allergic patients, checks study participant Carter Grodi, 16.

TAMPA, Fla. (Nov. 19, 2018) — With the New England Journal of Medicine’s publication yesterday of positive Phase 3 clinical trial results, a breakthrough oral immunotherapy for peanut-allergic children and adolescents is one step closer to becoming the first FDA-approved treatment for this potentially life-threatening food allergy.

The USF Health Morsani College of Medicine, Tampa, Fla., contributed to the long-anticipated PALISADE study reported in NEJM  – the largest randomized clinical trial to date for severely peanut-allergic patients looking for a preventive treatment to protect against accidental, possibly dangerous, exposures to peanuts.

USF Health was one of only two Florida sites that tested the safety and effectiveness of the investigational peanut allergy drug, known as AR101.  The biopharmaceutical company Aimmune Therapeutics developed AR101 – tiny, precisely measured amounts of powdered peanut protein held in pull-apart capsules until mixed in food — and makes the drug at its commercial manufacturing plant in Clearwater, Fla.

Aimmune Therapeutics plans to file for FDA approval by the end of this year.  If approved, the therapy could be available for use in children ages 4 to 17 by late 2019.

Tiny precisely measured amounts of powdered peanut protein, the investigational drug AR101 is held in pull-apart capsules until mixed in food.

For the pivotal PALISADE study, researchers at 66 sites across the United States, Canada and Europe evaluated whether gradual, controlled exposure to the substance (peanut proteins) that triggers allergic reactions could desensitize highly allergic children and adolescents, building up tolerance over 6 months and then continuing daily exposure thereafter.

“AR101 significantly improved peanut tolerance and was largely safe,” said USF Health allergist/immunologist Thomas Casale, MD, lead investigator of PALISADE study in Tampa Bay. Dr. Casale was a co-author of the NEJM paper, and serves on Aimmune’s scientific advisory board.  There were some side effects — a few severe, but most were mild to moderate, with gastrointestinal symptoms among the most common, he said.

“With appropriate administration, the AR101 immunotherapy can protect against accidental peanut exposures leading to costly emergency room visits and occasional fatalities,” said Dr. Casale, a professor in USF Health’s Division of Allergy and Immunology. “You still can’t chow down on a bag of peanuts at a baseball game, but it’s the accidental exposures that cause most problems. A treatment option that curtails risk and reduces allergic reactions could alleviate anxiety for these young patients and their parents.”

Currently, strictly avoiding peanuts is the only way to prevent a severe allergic reaction, and refills of costly auto-injectable epinephrine must be kept nearby and given within minutes to counteract hives, swelling of the tongue and throat, difficulty breathing, abdominal cramps and other unpredictable harmful effects. Despite parents’ best efforts, children may be accidentally exposed to peanuts when they swap snacks, consume an unsuspected ingredient in food, use a utensil with microscopic bits of peanut butter, or even inhale peanut particles from shells discarded in an enclosed baseball stadium.

Dr. Casale, a co-author on the New England Journal of Medicine paper, is a professor of medicine in the Division of Allergy and Immunology, USF Health Morsani College of Medicine.

Carolee Grodi is an Ocala, Fla. pharmacist whose 16-year-old son Carter was one of the first participants in USF’s arm of the PALISADE study.

Carter experienced an adverse allergic reaction, including hives, coughing and gasping for air, after eating a small peanut butter cracker as a toddler. His mother has been vigilant about screening any type of peanut or peanut product out of his diet ever since. So vigilant that Carter had virtually no other allergic reactions as he grew, and Carolee Grodi worried that as an increasingly social teen faced with peer pressure her son might not think about the risks.

“Accidental ingestion of peanuts was a constant worry whenever we went out to eat, or he attended a birthday party,” Grodi said. “Although this treatment is not a cure, it definitely helps guard against accidental exposure and offers our family some peace of mind.”

Even though Carter experienced sweating and mild nausea in reaction to his initial PALISADE peanut challenge (all carefully monitored for safety), he was eager to participate in helping test the new peanut allergy immune therapy.

“I wanted to see if I could build immunity so I wouldn’t have to worry so much about getting sick if someone with peanut butter on their hands bumps into me, or always have to be so cautious with every food label reading, ‘May contain peanuts’” he said.  “From my perspective, it’s been an extra layer of protection.”

The clinical research unit cart stocks auto-injectable epinephrine that can be administered to counteract severe allergic reactions.

In early November Carter was on a 300 mg. daily maintenance dose of AR101 – equivalent to one peanut – which he mixes with his food of choice, applesauce. He is now part of an Aimmune extended safety study.

At the start of the one-year PALISADE study, all 496 highly allergic participants, ages 4 to 17, tolerated a challenge test of no more than 30 mg. of peanut protein (equal to one-tenth of a peanut kernel) before experiencing symptoms. At the exit challenge, more than 67 percent of patients receiving active treatment (AR101) tolerated at least a single dose of 600 mg. of peanut protein – equal to 2 peanuts – compared to 4 percent of those receiving placebo. Half of the active treatment participants could eat a 1,000 mg dose — equal to 3 to 4 peanuts — in the exit food challenge.

USF Health continues to participate in ongoing studies to learn more about dosing of AR101 and long-term safety and effectiveness of peanut allergy immunotherapy, which may need to be maintained for years.

Up to 2.5 percent of children in the U.S. have been diagnosed with a peanut allergy, according to the American College of Allergy, Asthma and Immunology, with the incidence continuing to rise in the pediatric population.

-Photos by Torie M. Doll, USF Health Communications and Marketing