The Story Behind the First FDA-Approved Oral Immunotherapy (OIT) for Peanut Allergy
PALFORZIA finally for sale on America's medication marketplace
In addition to changes for food packaging labels, the Food and Drug Administration (FDA) has approved the very first therapy for treatment of peanut allergy.
By Allergic Living
November 9th, 2020
When the U.S. Food and Drug Administration (FDA) approved a new oral immunotherapy (OIT) for peanut allergy in children on January 31, 2020, it marked an important milestone. This biologic OIT drug, called PALFORZIA [Peanut (Arachis hypogaea) Allergen Powder-DNFP], became the first treatment approved by the FDA for people who are allergic to peanuts.
PALFORZIA can help reduce the severity of allergic reactions, including anaphylaxis, that may occur with accidental exposure to peanut. PALFORZIA may be started in patients aged 4 through 17 years old. Patients who turn 18 years of age while on PALFORZIA treatment should continue taking PALFORZIA unless otherwise instructed by their doctor. PALFORZIA does NOT treat allergic reactions and should not be given during an allergic reaction. Patients must maintain a strict peanut-free diet while taking PALFORZIA.
It is important to note that PALFORZIA can cause severe allergic reactions called anaphylaxis that may be life-threatening. Patients should stop taking PALFORZIA and get emergency medical treatment right away if they have any of the following symptoms after taking PALFORZIA: trouble breathing or wheezing, chest discomfort or tightness, throat tightness, trouble swallowing or speaking, swelling of your face, lips, eyes, or tongue, dizziness or fainting, severe stomach cramps or pain, vomiting, or diarrhea, hives (itchy, raised bumps on skin), or severe flushing of the skin. Because of the risk of severe allergic reactions, PALFORZIA is only available through a restricted program called the PALFORZIA Risk Evaluation and Mitigation Strategy (REMS) Program. Patients should talk to their healthcare provider for more information about the PALFORZIA REMS program and how to enroll.
The Roots of OIT
Pediatric allergists Dr. Wesley Burks of North Carolina Children’s Hospital and Dr. Stacie Jones of Arkansas Children’s Hospital, welcomed the news of the approval of PALFORZIA. It reminded them of all the families impacted by peanut allergy they have worked with over the last 19 years, including as investigators in the PALISADE clinical trial, which ultimately led to the FDA approval of the treatment.
“I’ve been so impressed by the families and kids who have been willing to collaborate with us to help find a new approach to treating peanut allergy,” says Dr. Jones, Director of the Arkansas Children’s Hospital Food Allergy Program and a professor of pediatrics at the University of Arkansas Medical School. “They wanted to do something and make a difference for themselves and for others.”
The day of the FDA approval, Dr. Burks, who is the Dean of the University of North Carolina School of Medicine, found it gratifying to think about “the future families and children who will now be able to be treated with an FDA-approved therapy for peanut allergy, rather than relying on avoidance of peanuts alone.”
Allergic Living spoke with Drs. Burks and Jones about the evolution of peanut allergy treatment, how peanut OIT and desensitization (a process that helps improve tolerability to specific food allergens) work, safety and possible side effects of the therapy and its potential benefits to families.
Drs. Burks and Jones were driven to work on a peanut allergy treatment because of the frustration experienced by patients and families who had to rely on avoidance alone.
During his first 15 years as a practicing allergist, Dr. Burks spent his time researching peanut allergy, intrigued about why it could be so severe and why patients seldom outgrew it. In the laboratory, he and his colleagues were able to identify all the different parts of the peanut that cause a reaction and learned how the immune system responds when it encounters a peanut.
But these insights did not help families looking for options to manage their children’s peanut allergy. Families were still living daily with the possibility that their child would be accidently exposed and suffer a severe reaction to even a trace amount of peanut.
In 2001, while at the University of Arkansas, Dr. Burks began to brainstorm with Dr. Jones and others about how to reduce a child’s sensitivity to peanuts by giving them small, then increasingly larger doses over time. This approach had worked for pollen allergies when given by injection, but could desensitization work for peanut allergy if it were given orally?
Although there had been limited success in Europe with this approach, no randomized, double-blind, placebo-controlled trials had been conducted. Considered the gold standard, these trials involve randomly assigning study participants to the study medicine or placebo, with neither the patient nor the investigator knowing which group they’re in.
Drs. Burks and Jones undertook small, controlled clinical trials with peanut OIT. As Dr. Burks moved on from Arkansas, he continued collaborating with Dr. Jones and other researchers. The amount of knowledge and published studies on oral immunotherapy grew, but the two allergists knew that a larger number of people with peanut allergy would need to be studied for the FDA to consider approving OIT for peanut allergy.
Putting OIT to the Test
In April 2011, parents of children with severe food allergies, patient advocacy organizations, allergists and other physicians, government representatives and members of the pharmaceutical industry participated in an advocacy-sponsored research retreat. The participants reached consensus about the need for an FDA-approved OIT food allergy therapy, one that could be standardized and consistently administered. The OIT protocol developed by Drs. Burks and Jones was the obvious candidate to move forward, starting with peanut allergy. According to Dr. Jones, the group "knew that it had to be applied to a much wider scale of patients to make sure that the science would hold up, would demonstrate clinical efficacy, and we could better understand the side effects."
The meeting ultimately led to the formation of a biopharmaceutical company (later called Aimmune Therapeutics and now known as Aimmune Therapeutics, a Nestlé Health Science company) to specifically address that need. The company would oversee the clinical development of PALFORZIA, which included the Phase 3 double-blind, placebo-controlled, randomized PALISADE study that involved 496 patients aged 4 through 17 and was conducted at 66 sites across 10 countries in North America and Europe. Of the 496 patients, 372 received PALFORZIA and 124 patients received a placebo (an inactive treatment that did not contain the study medication). This group included patients who may have started the trial but did not complete it. Of the patients who completed the full trial, 296 patients received PALFORZIA and 116 patients received placebo.
Participants assigned to PALFORZIA up-dosed with small, then gradually increasing amounts of the treatment over the course of six months, which were mixed into age-appropriate, refrigerated or room temperature food, such as applesauce or pudding, and then moved to a daily 300-miligram maintenance dose for another six months. The primary endpoint of the study (the specific event that the study is designed to assess the effect of the drugs upon) was the proportion of participants 4 through 17 years of age who had a response to the trial regimen, which was defined as the ability to ingest a single dose of 600 mg of peanut protein during the exit food challenge, with no more than mild allergic symptoms. At the start of the study, participants randomly assigned to receive PALFORZIA were able to tolerate no more than one-tenth of a peanut kernel (about 30 mg). By the exit food challenge after about 52 weeks of treatment, 67.2% of study participants (250 of 372) taking PALFORZIA were able to tolerate a single dose of 600 milligrams of peanut protein – about two peanut kernels – with no more than mild allergic symptoms compared with 4% of patients taking placebo (5 out of 124). The results from the study, which met its primary endpoint, were published in November 2018 in The New England Journal of Medicine, which was a notable success.
In the early days in his laboratory, Dr. Burks not only identified several important proteins as the allergens in peanut, but he also found the amount of them could vary significantly from one peanut to the next. For an FDA-approved oral immunotherapy, Aimmune’s leadership knew that dose consistency would be important. Aimmune put rigorous work into developing PALFORZIA as a pharmaceutical-grade oral immunotherapy with a well-defined allergen profile.
Managing Side Effects
PALFORZIA is intended to gradually reduce a child’s sensitivity to peanuts by giving them small, then increasingly larger doses over time. "With this approach, you’re not taking away the allergy, you’re trying to reduce the severity of allergic reactions, including anaphylaxis that may occur with accidental exposure to peanut," says Dr. Burks.
For families willing to experience some symptoms to reach the goal of reducing the severity of allergic reactions that may occur with accidental exposure to peanut, the PALISADE trial provided important insights.
The trial also defined the side effects of the treatment in detail. In the PALISADE trial, many participants experienced side effects, with most of them being mild to moderate and generally lasting no more than 40 minutes.
Dr. Burks says allergists trained to conduct OIT with PALFORZIA should inform families about what to expect in terms of gastrointestinal, skin, or respiratory symptoms. “This is important for an allergist to discuss with a family to allow for a good experience with the treatment.” Because of the risk of anaphylaxis, the FDA requires a Risk Evaluation and Mitigation Strategy (REMS) Program for PALFORZIA. This is a safety program that manages the risk of anaphylaxis associated with PALFORZIA to ensure the potential benefits of PALFORZIA outweigh its risks. The program requires that physicians, patients, healthcare settings and pharmacies must be certified and enrolled in the REMS Program to prescribe, receive, dispense, or administer PALFORZIA.
Deciding if PALFORZIA is Right for Your Family
To determine whether your family and child are good candidates for PALFORZIA, Dr. Burks says families must keep in mind that “PALFORZIA is not a cure and the peanut allergy will not go away.”
Families must understand that the goal of treatment with PALFORZIA is to help reduce the severity of allergic reactions, including anaphylaxis, that may occur with accidental exposure to peanut, and that side effects can occur. The first step is for your allergist to walk you through the protocol, in a shared decision-making process.
Dr. Jones has found that treating patients successfully with the newly approved OIT is the most rewarding part of her job as a pediatric allergist. "Many patients feel that the treatment was worth it."
Now that PALFORZIA is approved for peanut allergy, Drs. Burks and Jones hope it marks the start of a new era for how food allergies are treated. They are committed to advancing research to help families affected by other food allergies soon.
IMPORTANT SAFETY INFORMATION
PALFORZIA can cause severe allergic reactions called anaphylaxis that may be life-threatening.
- You will receive your first dose in a healthcare setting under the observation of trained healthcare staff.
- You will receive the first dose of all dose increases in a healthcare setting.
- In the healthcare setting, you will be observed for at least 1 hour for signs and symptoms of a severe allergic reaction.
- If you have a severe reaction during treatment, you will need to receive an injection of epinephrine immediately and get emergency medical help right away.
- You will return to the healthcare setting for any trouble tolerating your home doses.
Stop taking PALFORZIA and get emergency medical treatment right away if you have any of the following symptoms after taking PALFORZIA:
- Trouble breathing or wheezing
- Chest discomfort or tightness
- Throat tightness
- Trouble swallowing or speaking
- Swelling of your face, lips, eyes, or tongue
- Dizziness or fainting
- Severe stomach cramps or pain, vomiting, or diarrhea
- Hives (itchy, raised bumps on skin)
- Severe flushing of the skin
Because of the risk of severe allergic reactions, PALFORZIA is only available through a restricted program called the PALFORZIA Risk Evaluation and Mitigation Strategy (REMS) Program. Talk to your healthcare provider for more information about the PALFORZIA REMS program and how to enroll.
You should NOT take PALFORZIA if you have uncontrolled asthma, or if you ever had eosinophilic esophagitis (EoE) or other eosinophilic gastrointestinal disease.
Tell your doctor if you are not feeling well prior to starting treatment with PALFORZIA. Your doctor may decide to delay treatment until you are feeling better. Also tell your doctor about any medical conditions you have and if you are taking or have recently taken any other medicines, including medicines obtained without a prescription and herbal supplements.
Your doctor may decide that PALFORZIA is not the best treatment if:
- You are unwilling or unable to receive (or self-administer) injectable epinephrine.
- You have a condition or are taking a medication that reduces the ability to survive a severe allergic reaction.
What are the possible side effects of PALFORZIA?
The most commonly reported side effects of PALFORZIA were: stomach pain, vomiting, feeling sick, itching or burning in the mouth, throat irritation, cough, runny nose, sneezing, throat tightness, wheezing, shortness of breath, itchy skin, hives, and/or itchy ears.
PALFORZIA can cause severe allergic reactions called anaphylaxis that may be life-threatening.
PALFORZIA can cause stomach or gut symptoms including inflammation of the esophagus (called eosinophilic esophagitis). Symptoms of eosinophilic esophagitis can include:
- Trouble swallowing
- Food stuck in throat
- Burning in chest, mouth, or throat
- Regurgitation of undigested food
- Feeling sick
For additional information on the possible side effects of PALFORZIA, talk with your doctor or pharmacist.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.
Please see full Prescribing Information and Medication Guide, including an Important Warning about anaphylaxis.
This article was sponsored by Aimmune Therapeutics.
Dr. Wesley Burks and Dr. Stacie Jones did not receive compensation for this article.