Published analysis provides information about longer-term safety data of peanut allergy treatment

One of the most common food allergies in the U.S. is peanut allergy, a potentially life-long condition in which the immune system identifies even small amounts of peanut as harmful.¹ In the U.S. alone, approximately 1.3 million children between the ages of 4 through 17 years have peanut allergy.² Symptoms of allergic reactions after peanut exposure can develop within seconds. They can range from hives and digestive discomfort to potentially life-threatening anaphylaxis in which the throat and airways constrict.³ Even with appropriate and prompt treatment, severe reactions can be potentially life-threatening, although fatal reactions are rare.⁴

No cure is available, so children and their families must strictly avoid peanuts in order to prevent reactions. Yet, even with careful avoidance, inadvertent exposures to peanut can occur. According to a survey of 38,408 U.S. households between 2015 and 2016, one in five children reported more than one food allergy related emergency room visit in the previous year.¹

In January 2020, the peanut allergy community received welcome news when the U.S. Food and Drug Administration approved the first ever treatment for this condition — PALFORZIA^® [Peanut (Arachis hypogaea) Allergen Powder-dnfp]. Approved for children ages 4 through 17 years, PALFORZIA can help reduce the severity of allergic reactions, including anaphylaxis, that may occur with accidental exposure to peanut when used in conjunction with peanut avoidance and carrying injectable epinephrine. PALFORZIA does NOT treat allergic reactions and should not be given during an allergic reaction. This means the medical community can offer peanut-allergic children an approved treatment option in addition to avoidance. For allergists and parents of children with peanut allergy considering whether the treatment might be an option for them, safety is top of mind.

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CONTRAINDICATIONS

PALFORZIA is contraindicated in patients with uncontrolled asthma, or with a history of eosinophilic esophagitis and other eosinophilic gastrointestinal disease.

A pooled analysis of safety data published in The Journal of Allergy and Clinical Immunology (JACI) may provide important insights about the longer-term safety profile of PALFORZIA.⁵ The analysis was sponsored by Aimmune Therapeutics, a Nestlé Health Science company, and along with the FDA-approved labeling, the analysis may help facilitate shared decision-making between allergists and families impacted by peanut allergy about whether the treatment could be right for them.

Dr. Thomas B. Casale, one of the authors of the publication, shares key findings from the analysis and discusses how the results can act as an important resource for discussions among allergists and families impacted by peanut allergy. Dr. Casale has extensive experience with peanut allergy management. He is a professor of medicine and pediatrics and chief of clinical and translational research in the Division of Allergy and Immunology at the University of South Florida in Tampa. He also serves as the chief medical advisor for FARE (Food Allergy Research and Education) and is the former president of the American Academy of Allergy, Asthma & Immunology (AAAAI). Aimmune Therapeutics – Nestlé Health Science is a FARE corporate partner and Dr. Casale is a paid advisor to Aimmune Therapeutics.

Q: Can you tell us more about PALFORZIA?

A: PALFORZIA was approved as an oral immunotherapy (OIT) for the mitigation of allergic reactions, including anaphylaxis, that may occur with accidental exposure to peanut for patients aged 4 through 17 years with a confirmed diagnosis of peanut allergy. PALFORZIA is not indicated for the emergency treatment of allergic reactions, including anaphylaxis. PALFORZIA is to be used in conjunction with a peanut-avoidant diet and patients must continue to carry injectable epinephrine. PALFORZIA is used with a structured dosing approach. With OIT, the specific allergenic proteins are ingested initially in very small quantities. This is followed by incrementally increasing amounts, potentially resulting in the ability to mitigate allergic reactions to the allergen over time.

Q: How can PALFORZIA help?

A: PALFORZIA is intended to help a child gradually decrease their sensitivity to peanuts over time. The first part of the process, “Initial Dose Escalation,” takes place in a clinician’s office and lasts about four hours. The child is given small doses of peanut protein from 0.5 mg to 6 mg. If they can tolerate at least 3 mg, they can move to “Up-Dosing,” which takes about six months. During that time, consistent, precise amounts of peanut protein are given every day, and the dose is increased every two weeks if tolerated. The first dose of each new Up-Dosing level is administered in a healthcare setting to manage potentially severe allergic reactions, including anaphylaxis. After completing the Up-Dosing phase, the child starts taking a “Maintenance” dose every day. The Maintenance phase continues over time to help the child maintain their decreased sensitivity to peanut. The most common adverse events reported in individuals treated with PALFORZIA (incidence ≥5% and at least 5% greater than placebo) are abdominal pain, vomiting, nausea, oral pruritus, oral paresthesia, throat irritation, cough, rhinorrhea, sneezing, throat tightness, wheezing, dyspnea, pruritus, urticaria, anaphylactic reaction, and ear pruritus.

Q: How has PALFORZIA changed the way you treat patients with peanut allergy?

A: Every day, children with peanut allergy must live with this condition, which can restrict their ability to eat at a restaurant or a friend’s birthday party, for example. For someone with peanut allergy, the number one management strategy is peanut avoidance alone, but it’s not always effective because peanuts can be difficult to avoid. Aside from where peanuts are obviously visible, they are often found in baked goods and candy and are sometimes found in African, Asian, and Mexican dishes.^[6] Even foods that do not contain peanuts could have cross-contact with peanuts during manufacturing^[7] or food preparation, putting patients at risk of exposure. Because peanuts are so ubiquitous, a family’s daily life can be dominated by efforts to avoid peanut exposure.

With PALFORZIA, we have an FDA-approved, pharmaceutical-grade OIT for peanut allergy, for patients aged 4 through 17 years, with a well-defined allergen profile to ensure that every dose has been prepared and analyzed for consistency. PALFORZIA is to be used in conjunction with a peanut-avoidant diet and patients must continue to carry injectable epinephrine. With safety top of mind for my patients and their families, this pooled analysis of PALFORZIA safety data — the largest safety data analysis of a single OIT formulation for peanut allergy — provides information for shared decision-making that I encourage allergists to consider when speaking to their patients about PALFORZIA.

Q: What are some key considerations for parents/caregivers when deciding whether PALFORZIA is right for their child?

A: Shared decision-making with patients and families is critically important. The patient and family must be fully vested in PALFORZIA because it requires a commitment to all three phases — Initial Dose Escalation, Up-Dosing, and Maintenance. The family is especially important in empowering the child by supporting them to get through the Up-Dosing phase and stay on Maintenance therapy.

As I mentioned, keeping the safety of the child in mind during the treatment process is critical and is a big part of the decision of whether to move forward with treatment. I discuss with my patients that each dosage increase during PALFORZIA Up-Dosing is administered in the controlled environment of an allergist’s office, where an allergic reaction can be addressed right away by medical staff. PALFORZIA can cause anaphylaxis, which may be life threatening and can occur at any time during PALFORZIA therapy. That is very different from experiencing an allergic reaction resulting from an accidental exposure to peanut in an uncontrolled environment without medical supervision or close monitoring by the caregiver.

As the pooled analysis in JACI showed, it is crucial for allergists to contextualize the risk of anaphylactic reactions with PALFORZIA versus an accidental exposure and to consider the risk/benefit of the treatment as perceived by the patient and family. Systemic allergic reactions after accidental exposure are inherently unpredictable and may occur at a time and place where patients and their families are unable to manage the reaction effectively. In comparison, the pooled analysis showed that systemic allergic reactions related to PALFORZIA occurred at the time of dosing, when the individual and their family are more likely to be prepared and can exert greater control in managing allergic reactions.⁵

Q: What else can you tell us about the pooled analysis published in JACI and why the findings are important for allergists treating patients with peanut allergy?

A: The findings from this Aimmune-sponsored study, which were published in JACI, can be a useful resource for allergists when having discussions with patients and their caregivers about whether treatment with PALFORZIA is right for them, especially if parents are concerned about safety. The JACI publication included clinical data from a pooled analysis of three controlled Phase 3 and two open-label extension trials of PALFORZIA in which approximately 10% of the 944 participants had received at least one dose and up to two years of treatment (median exposure ≈49 weeks). Given differences in trial designs and extent of treatment exposure, no formal inferential statistical comparisons were conducted. The safety data were summarized by treatment group using appropriate descriptive statistics. The analysis showed a consistent and manageable safety profile over time. The most frequently reported adverse events were primarily respiratory or gastrointestinal in nature, such as throat irritation, abdominal pain, oral pruritus, and nausea. Most adverse events were mild to moderate and resolved rapidly, and most reactions occurred during Up-Dosing and were less frequent and less severe once patients were on Maintenance therapy.

I would advise allergists to clearly spell out the benefits and risks of this treatment and refer to the JACI data as a resource when discussing the safety of PALFORZIA.

Q: Why is PALFORZIA an important treatment option for the peanut allergy community?

A: With PALFORZIA, children aged 4 through 17 years with peanut allergy have an FDA-approved treatment option that can help mitigate the severity of allergic reactions when used in conjunction with peanut avoidance. PALFORZIA is not indicated for the emergency treatment of allergic reactions, including anaphylaxis.

Please see additional information after Important Safety Information.

IMPORTANT SAFETY INFORMATION (CONTINUED)

WARNINGS AND PRECAUTIONS

ANAPHYLAXIS

PALFORZIA can cause anaphylaxis, which may be life threatening. PALFORZIA is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the PALFORZIA REMS because of the risk of anaphylaxis. Only prescribers, healthcare settings, pharmacies, and patients certified and enrolled in the REMS Program can prescribe, receive, dispense or administer PALFORZIA.

Anaphylaxis has been reported during all phases of PALFORZIA dosing, including Maintenance and in subjects who have undergone recommended Up-Dosing and dose modification procedures.

Do not initiate PALFORZIA treatment in a patient who has had severe or life-threatening anaphylaxis within the previous 60 days. PALFORZIA may not be suitable for patients with certain medical conditions that may reduce the ability to survive anaphylaxis, including but not limited to markedly compromised lung function, severe mast cell disorder, or cardiovascular disease. In addition, PALFORZIA may not be suitable for patients taking medications that can inhibit or potentiate the effects of epinephrine.

All Initial Dose Escalation doses and the first dose of each Up-Dosing level must be administered under observation in a certified health care setting.

Patients may be more likely to experience allergic reactions following PALFORZIA administration in the presence of cofactors such as exercise, hot water exposure, intercurrent illness (e.g., viral infection), or fasting. Other potential cofactors may include menstruation, sleep deprivation, nonsteroidal anti-inflammatory drug use, or uncontrolled asthma. Patients should be proactively counseled about the potential for the increased risk of anaphylaxis in the presence of these cofactors. If possible, adjust the time of dosing to avoid these cofactors. If it is not possible to avoid these cofactors, consider withholding PALFORZIA temporarily.

ASTHMA

Uncontrolled asthma is a risk factor for a serious outcome, including death, in anaphylaxis. Ensure patients with asthma have their asthma under control prior to initiation of PALFORZIA.

PALFORZIA should be temporarily withheld if the patient is experiencing an acute asthma exacerbation. Following resolution of the exacerbation, resumption of PALFORZIA should be undertaken cautiously. Re-evaluate patients who have recurrent asthma exacerbations and consider discontinuation of PALFORZIA.

EOSINOPHILIC GASTROINTESTINAL DISEASE

Discontinue PALFORZIA and consider a diagnosis of eosinophilic esophagitis in patients who experience severe or persistent gastrointestinal symptoms, including dysphagia, vomiting, nausea, gastroesophageal reflux, chest pain, or abdominal pain.

GASTROINTESTINAL ADVERSE REACTIONS

Gastrointestinal adverse reactions were commonly reported in PALFORZIA-treated subjects, and dose modification should be considered for patients who report these reactions. For severe or persistent gastrointestinal symptoms consider a diagnosis of eosinophilic esophagitis.

ADVERSE REACTIONS

The most common adverse events reported in subjects treated with PALFORZIA (incidence ≥ 5% and at least 5% greater than placebo) are abdominal pain, vomiting, nausea, oral pruritus, oral paresthesia, throat irritation, cough, rhinorrhea, sneezing, throat tightness, wheezing, dyspnea, pruritus, urticaria, anaphylactic reaction, and ear pruritus.

INDICATION

PALFORZIA is an oral immunotherapy indicated for the mitigation of allergic reactions, including anaphylaxis, that may occur with accidental exposure to peanut. PALFORZIA is approved for use in patients with a confirmed diagnosis of peanut allergy. Initial Dose Escalation may be administered to patients aged 4 through 17 years. Up-Dosing and Maintenance may be continued in patients 4 years of age and older.

PALFORZIA is to be used in conjunction with a peanut-avoidant diet.

Limitation of Use: Not indicated for the emergency treatment of allergic reactions, including anaphylaxis.

Please see full Prescribing Information, including Boxed WARNING, and Medication Guide.

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.

For more information, visit www.PALFORZIApro.com.

References

[1] Gupta RS, Warren CM, Smith BM, et al. The public health impact of parent-reported childhood food allergies in the United States. Pediatrics. 2018;142(6):e20181235.
[2] Mahr, T., Lieberman, J.A., Haselkorn, T., et al. Characteristics of Peanut Allergy Diagnosis in a US Health Care Claims Database (2011-2017). J Allergy Clin Immunol Pract. 2021 9(4),1683-1694.e5. https://doi.org/10.1016/j.jaip.2020.12.020
[3] American College of Allergy, Asthma & Immunology. Accessed December 20, 2019.
^{[4 ]}Wiley Online Library. The global burden of illness of peanut allergy: A comprehensive literature review. Accessed July 18, 2022. https://onlinelibrary.wiley.com/doi/10.1111/all.14666.
https://acaai.org/allergies/types/food-allergies/types-food-allergy/peanut-allergy.
^[5]Brown KR, Baker J, Vereda A, et al. Safety of peanut (Arachis hypogaea) allergen powder-dnfp in children and teenagers with  peanut allergy: Pooled summary of phase 3 and extension trials. J Allergy Clin Immunol. 2021. DOI:https://doi.org/10.1016/j.jaci.2021.12.780.
[6] FARE. Your Food Allergy Field Guide Accessed. April 13, 2022. https://www.arts-cs.org/_theme/files/Student%20Life/Food-Alergy-Field-Guide.pdf.
[7] Stanford Children’s Health. Peanut Allergy Diet. Important Point. Accessed April 13, 2022.  https://www.stanfordchildrens.org/en/topic/default?id=peanut-allergy-diet-85-P00028.

PALF-PM-USA 0148 08/22