Biologics for Food Allergy

Educational Objectives

The goal of this program is to improve management of food allergy (FA). After hearing and assimilating this program, the clinician will be better able to:

1. Appraise different types of biologics being studied for management of FA.
2. Summarize the benefits and limitations of omalizumab for FA.

Summary

Food allergy (FA): biologics for FA have seen significant progress, especially with the recent approval of omalizumab; this development marked a breakthrough, and ongoing research is exploring other drugs for FA treatment; mast cell inhibitors, initially trialed for chronic spontaneous urticaria, are now being considered for FA

Biologics for FA: the epithelium produces various alarmins in response to stimuli; anti-thymic stromal lymphopoietin is already approved for asthma and is undergoing trials for FA; therapies targeting interleukin-33 (IL-33), another alarmin, have shown promising results in blocking peanut-induced allergic reactions; mast cells play a crucial role in FA, and Syk inhibitors, Janus kinase (JAK) inhibitors, and Bruton tyrosine kinase (BTK) inhibitors are being studied; blocking immunoglobulin E (IgE), the major antibody in FA pathogenesis, is another strategy; one novel approach involves targeting pre-B cells and then treating with dupilumab to prevent IgE production and achieve long-term remission

Omalizumab: reduces IgE rapidly but requires time to eliminate cell-bound IgE on the high-affinity fragment crystallizable epsilon receptor I receptors; this explains why patients on omalizumab cannot immediately start consuming allergens (eg, peanuts); historical data from >20 yr ago showed that anti-IgE molecules could inhibit peanut-induced allergic responses, although not all patients responded; legal disputes between 2 companies halted the development of the previous molecule, while development of omalizumab continued; numerous small studies demonstrated omalizumab’s efficacy in blocking allergic-induced food responses as a monotherapy and may increase the threshold for allergic symptoms during oral immunotherapy (OIT); adding omalizumab to OIT makes OIT safer by removing the IgE, but it is currently not known if omalizumab is more effective; the OUtMATCH trial by Wood et al (2024) led to approval of omalizumab by the US Food and Drug Administration (FDA); stage 2 of the trial is investigating use of omalizumab with OIT

OIT for food allergies: differs from environmental allergens; for environmental allergies, a substantial proportion of patients achieve long-standing remission after several years of therapy; this has not been demonstrated for food allergies

OUtMATCH trial (Wood et al [2024]): included 165 patients, with 110 patients receiving omalizumab and 55 patients receiving placebo; after 16 to 20 wk, 68% of omalizumab recipients could consume 600 mg of peanut protein (vs 5% on placebo); secondary endpoints included the ability to tolerate ≥1000 mg of other allergens (eg, cashew, milk, egg) with varying success rates; some patients who did not meet the primary endpoint achieved partial protection, tolerating >100 mg of peanut and ≥300 mg of other allergens; ≈50% of the patients could tolerate 2000 mg of peanut protein; the extension phase of the OUtMATCH study confirmed that patients who switched from placebo to omalizumab responded similarly, and those initially treated maintained their protection for 24 to 28 additional wk

Clinical aspects of OUtMATCH study: establishing diagnostic criteria for eligibility is crucial; many practitioners rely on a combination of patient history and antigen-specific IgE levels, sometimes skipping food challenges; determining the appropriate dosage is another challenge; access to biologics, especially for patients who are low income and in underrepresented minority groups, is a concern; additionally, omalizumab is not approved for FA in Europe; assessing treatment responsiveness is challenging because skin tests and antigen-specific IgE are unreliable; a food challenge is the only accurate method to confirm protection; determining when to stop omalizumab is also difficult, particularly for children who may outgrow allergies (eg, milk, egg); patients must continue carrying epinephrine and avoiding allergens because omalizumab protects against only small quantities of allergen

Limitations of the OUtMATCH study: this study excluded patients >55 yr of age and those with severe anaphylaxis, but treating these populations remains important because of their risk for worse outcomes; concerns about food allergies other than those studied in the trial are minimal because omalizumab’s mechanism should work universally; unlike most trials that start with adults, the OUtMATCH study included only 3 adults, with the rest being children; assessing the cost-benefit ratio and safety in very young patients (1-6 yr of age) is another area needing more data; the ongoing study is investigating whether combining omalizumab with immunotherapy provides an advantage over omalizumab alone

Other biologics for FA: various immunotherapy regimens are being explored, either as monotherapy or in combination with biologics; while peanut allergen powder-dfnp (Palforzia) is the only FDA-approved product for OIT, sublingual immunotherapy appears safer; variability in allergen content across commercial product batches is significant and raises concerns when considering homemade immunotherapy; critical questions include optimal duration for maintenance therapy, optimal regimen, and ways to treat multiple food allergies; a recent paper on multiple concurrent OITs demonstrated effectiveness

Ligelizumab: an anti-IgE molecule with improved pharmacokinetics compared with omalizumab; its FA trial was halted, leaving its development uncertain

Alarmins: research, particularly with IL-33 inhibitors, showed promising results; a single injection of a monoclonal antibody against IL-33 allowed some participants to tolerate higher doses of peanuts

Anti-thymic stromal lymphopoietin: is being investigated, while strategies to target mast cells include depleting them with C-KIT inhibitors, blocking key mediators (eg, IL-4, IL-13), inhibiting activation with BTK and JAK inhibitors, or silencing the mast cell with Siglec-6 or Siglec-8

Dupilumab: monotherapy for peanut allergy yielded no success; using dupilumab as an adjunct to AR101 (Palforzia) and other OITs was ineffective; an upcoming study aims to use a B-cell maturation antigen CD3 bispecific antibody to eliminate IgE-producing plasma cells while preventing the production of IL-4 and IL-13 through dupilumab; this proof-of-concept study is combining dupilumab with monoclonal antibodies before transitioning to long-term dupilumab use in a small patient group

BTK inhibitors: a study demonstrated significant inhibition of skin tests and basophil activation after 2 days of treatment with acalabrutinib; another BTK inhibitor, remibrutinib, is being studied and may be approved soon for chronic spontaneous urticaria

JAK inhibitors: are also being examined for their ability to block basophil activation tests and skin tests

Readings

Casale TB, Fiocchi A, Greenhawt M. A practical guide for implementing omalizumab therapy for food allergy. J Allergy Clin Immunol. 2024;153(6):1510-1517. doi:10.1016/j.jaci.2024.03.019; Dispenza MC. The use of Bruton's tyrosine kinase inhibitors to treat allergic disorders. Curr Treat Options Allergy. 2021;8(3):261-273. doi:10.1007/s40521-021-00286-y; Groetch M, Mudd K, Woch M, et al. Retail food equivalents for post-oral immunotherapy dosing in the Omalizumab as Monotherapy and as Adjunct Therapy to Multi-Allergen Oral Immunotherapy in Food-Allergic Children and Adults (OUtMATCH) Clinical Trial. J Allergy Clin Immunol Pract. 2023;11(2):572-580.e2. doi:10.1016/j.jaip.2022.10.022; Sindher SB, Nadeau KC, Chinthrajah RS, et al. Efficacy and safety of dupilumab in children with peanut allergy: a multicenter, open-label, phase II study. Allergy. 2025;80(1):227-237. doi:10.1111/all.16404; Wang SH, Zuo YG. Thymic stromal lymphopoietin in cutaneous immune-mediated diseases. Front Immunol. 2021;12:698522. doi:10.3389/fimmu.2021.698522; Wood RA, Chinthrajah RS, Rudman Spergel AK, et al. Protocol design and synopsis: Omalizumab as Monotherapy and as Adjunct Therapy to Multiallergen OIT in Children and Adults with Food Allergy (OUtMATCH). J Allergy Clin Immunol Glob. 2022;1(4):225-232. Published 2022 Jul 21. doi:10.1016/j.jacig.2022.05.006; Wood RA, Togias A, Sicherer SH, et al. Omalizumab for the treatment of multiple food allergies. N Engl J Med. 2024;390(10):889-899. doi:10.1056/NEJMoa2312382.

Disclosures

For this program, the following relevant financial relationships were disclosed and mitigated to ensure that no commercial bias has been inserted into this content: Dr. Casale has been a consultant and member of the advisory board for ARS, Celldex, Eli Lilly, FARE, Genentech, Jasper, Novartis, Regeneron, and Sanofi; has received research grants from Alakos, Celldex, DBV, Escient, Genentech, Jasper, Leo, Novartis, Regeneron, and Sanofi; and has been on the speaker's bureau and/or received honoraria from ARS, Genentech, and Sanofi. Members of the planning committee reported nothing relevant to disclose. Dr. Casale's lecture includes information related to the off-label or investigational use of a therapy, product, or device.

Acknowledgements

Dr. Casale was recorded at 2025 Symposium Update in Allergy and Immunology and Rhinoscopy Hands-On Workshop, held January 17-18, 2025, in Tampa, FL, and presented by USF Health. For information about upcoming CME activities from this presenter, please visit https://health.usf.edu/cpd. Audio Digest thanks the speakers and USF Health for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 1.00 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 1.00 CE contact hours.

Lecture ID:

OT580901

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.