The safety and efficacy of XOLAIR was evaluated in a multi-center, randomized, double-blind, placebo-controlled Food Allergy (FA) trial [NCT03881696] in 168 adult patients and pediatric patients 1 year of age to less than 56 years who were allergic to peanut and at least two other foods, including milk, egg, wheat, cashew, hazelnut, or walnut (i.e., studied foods). The FA trial enrolled patients who experienced dose-limiting symptoms (e.g., moderate to severe skin, respiratory or gastrointestinal symptoms) to a single dose of ≤100 mg of peanut protein and ≤300 mg protein for each of the other two foods (milk, egg, wheat, cashew, hazelnut, or walnut) during the screening double-blind placebo-controlled food challenge (DBPCFC). Patients with a history of severe anaphylaxis (defined as neurological compromise or requiring intubation) were excluded from the study. Patients were randomized 2:1 to receive a subcutaneous dosage of XOLAIR or placebo based on serum total IgE level (IU/mL), measured before the start of treatment, and by body weight according to Table 4 [see Dosage and Administration (2.4)] for 16 to 20 weeks. After 16 to 20 weeks of treatment, each patient completed a DBPCFC consisting of placebo and each of their 3 studied foods. Following the DBPCFC, the first 60 patients that included 59 pediatric patients and one adult patient who completed the double-blind, placebo-controlled phase of the study could continue to receive XOLAIR in a 24 to 28 week open-label extension.

Efficacy of XOLAIR is based on 165 pediatric patients who were included in the efficacy analyses provided below. The mean age of the pediatric patients was 8 years (age range: 1 to 17 years); 37% were less than 6 years of age, 38% were 6 to less than 12 years of age, and 25% were 12 to less than 18 years of age. Patient population were 56% male, 63% White, 13% Asian, 7% Black, 16% Other, and 55% of patients had a history of asthma.

The primary efficacy endpoint was the percentage of patients who were able to consume a single dose of ≥600 mg of peanut protein without dose-limiting symptoms (e.g., moderate to severe skin, respiratory or gastrointestinal symptoms) during DBPCFC. Table 16 shows XOLAIR treatment led to a statistically higher response rate (68%) than placebo (5%).

The secondary efficacy endpoints were the percentage of patients who were able to consume a single dose of ≥1000 mg of cashew, milk, or egg protein without dose-limiting symptoms during DBPCFC. The study met the secondary endpoints and demonstrated that XOLAIR treatment led to statistically higher response rates than placebo for all three foods. See Table 16 for details.

Seventeen percent of XOLAIR treated patients were not able to consume >100 mg of peanut protein without moderate to severe dose-limiting symptoms. Eighteen, 22, and 41 percent of XOLAIR-treated patients were not able to consume >300 mg of milk, egg, or cashew protein, respectively, without moderate to severe dose-limiting symptoms.

Additional secondary analyses included the percentage of patients who were able to consume at least two or all three foods during DBPCFC. For two foods, 71% of XOLAIR treated patients were able to consume a single dose of ≥600 mg versus 5% in the placebo group and 67% were able to consume a single dose of ≥1000 mg versus 4% in the placebo group. For a single dose of ≥600 mg of three foods, the response rates were 48% in the XOLAIR group versus 4% in the placebo group and for a single dose of ≥1000 mg of three foods, the response rate in the XOLAIR group was 39% while none of the placebo patients were able to consume the challenge dose without symptoms.

The effectiveness of XOLAIR in adults is supported by the adequate and well-controlled trial of XOLAIR in pediatric patients, disease similarity in pediatric and adult patients, and pharmacokinetic (PK) similarity [see Clinical Pharmacology (12.3)].

While efficacy cannot be established from uncontrolled, open-label studies, for 38 pediatric patients who continued XOLAIR for 24-28 weeks in an open-label extension, the percentage of patients who were able to consume ≥600 mg of peanut protein and ≥1000 mg of egg, milk, and/or cashew protein without moderate to severe dose-limiting symptoms was maintained.