Xolair

Two placebo-controlled, multiple-dose clinical trials of 24 weeks’ duration (CSU Trial 1; n= 319) and 12 weeks’ duration (CSU Trial 2; n=322).

• Patients received Xolair 75mg, 150mg, or 300mg or placebo by SC injection every 4 weeks in addition to their baseline level of H₁ antihistamine therapy for 24 or 12 weeks, followed by a 16-week washout observation period.
• A total of 640 patients (165 males, 475 females) were included for the efficacy analyses; 84% white; median age, 42 years (range, 12-72).
• In both trials, patients who received Xolair 150mg or 300mg had greater decreases from baseline in weekly itch severity scores and weekly hive count scores than placebo at week 12.
• The 75mg dose did not demonstrate consistent evidence of efficacy and is not approved for use in CSU.
• The appropriate duration of therapy for CSU with Xolair has not been determined.
• A larger proportion of patients treated with Xolair 300mg reported no itch and no hives at week 12 compared with patients treated with Xolair 150mg, Xolair 75mg, and placebo.

Safety and efficacy of Xolair were evaluated in 3 randomized, double-blind, placebo-controlled, multicenter trials.

Asthma Trials 1 and 2

Patient demographics

• Forced expiratory volume in one second (FEV1) between 40% and 80% predicted.
• FEV₁ improvement of at least 12% following beta2-agonist administration.
• Symptomatic and being treated with inhaled corticosteroids (ICS) and short-acting beta2-agonists.

Trials included a run-in period to achieve a stable conversion to a common ICS (beclomethasone dipropionate), followed by randomization to Xolair or placebo. 

Patients received Xolair for 16 weeks with an unchanged corticosteroid dose unless an acute exacerbation necessitated an increase. 

Patients then entered an ICS reduction phase of 12 weeks during which ICS dose reduction was attempted in a stepwise manner.

In both trials, the number of exacerbations per patient was reduced in patients treated with Xolair compared with placebo

Asthma Trial 3

Patient demographics

• No restriction on screening FEV1.
• Long-acting beta2 agonists allowed.
• Patients were receiving at least 1000mcg/day fluticasone propionate and a subset was also receiving oral corticosteroids.

Trial consisted of a run-in period to achieve a stable conversion to a common ICS (fluticasone propionate), followed by randomization to Xolair or placebo.

Patients received Xolair for 16 weeks with an unchanged corticosteroid dose unless an acute exacerbation necessitated an increase. 

Patients then entered an ICS reduction phase of 16 weeks during which ICS or oral steroid dose reduction was attempted in a stepwise manner.

The number of exacerbations in patients treated with Xolair was similar to that in placebo treated patients.

In all 3 trials, a reduction of asthma exacerbations was not observed in Xolair-treated patients who had FEV₁>80% at the time of randomization. Reductions in exacerbations were not seen in patients who required oral steroids as maintenance therapy.

Asthma Trial 4

628 pediatric patients 6 to <12 years of age with moderate to severe asthma inadequately controlled despite use of ICS (fluticasone propionate DPI ≥200mcg/day or equivalent) with or without other controller asthma medications.

Patient demographics

• Diagnosis of asthma >1 year.
• Positive skin prick test to at least 1 perennial aeroallergen.
• History of clinical features (eg, daytime/nighttime symptoms, exacerbations within the year prior to study entry).

First 24 weeks, steroid doses remained constant from baseline, followed by a 28-week period during which ICS adjustment was allowed.

At 24 weeks, the Xolair group had a statistically significantly lower rate of asthma exacerbations (0.45 vs. 0.64) with an estimated rate ratio of 0.69 (95% CI, 0.53-0.90). 

The Xolair group also had a lower rate of asthma exacerbations vs placebo over the full 52-week double-blind treatment period (0.78 vs. 1.36; rate ratio: 0.57; 95% CI, 0.45-0.72).

Asthma Trial 5

334 pediatric patients, 298 of whom were 6 to <12 years of age, with moderate to severe asthma who were well-controlled with inhaled corticosteroids (beclomethasone dipropionate 168-420mcg/day).

A 16-week steroid treatment period was followed by a 12-week steroid dose reduction period.

Patients treated with Xolair had fewer asthma exacerbations vs placebo during both the 16-week fixed steroid treatment period (0.18 vs. 0.32; rate ratio: 0.58; 95% CI, 0.35-0.96) and the 28-week treatment period (0.38 vs. 0.76; rate ratio: 0.50; 95% CI, 0.36-0.71).

Approval was supported by data from the phase 3 POLYP 1 (N=138) and POLYP 2 (N=127) trials evaluating the efficacy and safety of Xolair in adults with nasal polyps who had an inadequate response to nasal corticosteroids.

Patients  were required to have evidence of bilateral polyps as determined by a nasal polyp score (NPS)≥5 with NPS≥2 in each nostril, despite use of nasal mometasone during the run-in period.

Patients were randomly assigned to receive either Xolair or placebo by subcutaneous injection every 2 to 4 weeks. 

The coprimary end points for both trials were change from baseline in NPS at week 24, and change from baseline in average daily Nasal Congestion Score (NCS) to week 24.

Results from both trials showed that patients treated with Xolair had a statistically significant greater improvement from baseline at week 24 in NPS and NCS compared with placebo, with improvements observed as early as week 4.

Xolair demonstrated statistically significant improvements on sense of smell score, post-nasal drip, and runny nose in both trials.