BACKGROUNDIgE-mediated
anaphylaxis is a potentially fatal systemic
allergic reaction for which there are no currently FDA-approved preventative
therapies.
Bruton's tyrosine kinase (BTK) is an essential
enzyme for
IgE-mediated signaling pathways and is an ideal pharmacologic target to prevent
allergic reactions. In this open-label trial, we evaluated the safety and efficacy of
acalabrutinib, a BTK inhibitor that is FDA approved to treat some B cell
malignancies, in preventing clinical reactivity to peanut in adults with
peanut allergy.METHODSAfter undergoing graded oral peanut challenge to establish their baseline level of clinical reactivity, 10 patients had a 6-week rest period, then received 4 standard doses of 100 mg
acalabrutinib twice daily and underwent repeat food challenge. The primary endpoint was the change in patients' threshold dose of peanut
protein to elicit an objective clinical reaction.RESULTSAt baseline, patients tolerated a median of 29 mg of peanut
protein before objective clinical reaction. During subsequent food challenge on
acalabrutinib, patients' median tolerated dose significantly increased to 4,044 mg (range 444-4,044 mg). 7 patients tolerated the maximum protocol amount (4,044 mg) of peanut
protein with no clinical reaction, and the other 3 patients' peanut tolerance increased between 32- and 217-fold. 3 patients experienced a total of 4 adverse events that were considered to be possibly related to
acalabrutinib; all events were transient and nonserious.CONCLUSIONAcalabrutinib pretreatment achieved clinically relevant increases in patients' tolerance to their food
allergen, thereby supporting the need for larger, placebo-controlled trials.TRIAL REGISTRATIONClinicalTrials.gov NCT05038904FUNDINGAstraZeneca
Pharmaceuticals, the Johns Hopkins Institute for Clinical and Translational Research, the Ludwig Family Foundation, and NIH grants AI143965 and AI106043.