CINQAIR Rx

The asthma development program for Cinqair 3 mg/kg (administered once every 4 weeks) included 4 randomized, double-blind, placebo-controlled studies (Studies I-IV) 16 to 52 weeks in duration involving 981 patients ≥12 years of age. While patients aged 12-17 years were included in these trials, Cinqair is not approved for use in this age group. All patients continued their background asthma therapy throughout the duration of the studies.

Studies I and II 

• Studies I and II were 52-week studies in 953 patients with asthma who were required to have a blood eosinophil count of ≥400/mcL (within 3 to 4 weeks of dosing), and ≥1 asthma exacerbation requiring systemic corticosteroid use over the past 12 months.
• The majority of patients (82%) were on medium-high dose inhaled corticosteroids plus a long-acting beta agonist (ICS/LABA) at baseline. 
• Maintenance oral corticosteroids (OCS) (up to prednisone 10 mg/day or equivalent) were allowed. 
• Cinqair 3 mg/kg administered once every 4 weeks for a total of 13 doses was evaluated vs placebo. 

Study III 

• Study III was a 16-week study in 315 patients who were required to have a blood eosinophil count of ≥400/mcL at screening (within 3 to 4 weeks of dosing).
• Maintenance OCS were not allowed.
• Cinqair 3 mg/kg or 0.3 mg/kg administered once every 4 weeks for a total of 4 doses was evaluated vs placebo.
• While 2 doses of Cinqair were studied, Cinqair 3 mg/kg is the only recommended dose. 

Study IV 

• Study IV was a 16-week study in 496 patients unselected for baseline blood eosinophil levels (~80% of patients had a screening [within 3 to 4 weeks of dosing] blood eosinophil count of <400/mcL).
• Maintenance OCS were not allowed.
• Cinqair 3 mg/kg administered once every 4 weeks for a total of 4 doses was evaluated vs placebo.

Exacerbations 
The primary endpoint for Studies I and II was the frequency of asthma exacerbations for each patient during the 52-week treatment period. 

• Patients receiving Cinqair 3 mg/kg once every 4 weeks had significant reductions in the rate of all asthma exacerbations vs placebo (Study I: 0.5 [95% CI, 0.37-0.67]; Study II: 0.41 [95% CI, 0.28-0.59]).  
• Exacerbations requiring systemic corticosteroid use were also reduced in the Cinqair group vs placebo (Study I: 0.45 [95% CI, 0.33-0.62]; Study II: 0.39 [95% CI, 0.27-0.58]).
• Exacerbations resulting in a hospitalization and/or ER visit were also reduced in the Cinqair group vs placebo (Study I: 0.66 [95% CI, 0.32-1.36]; Study II: 0.69 [95% CI, 0.29-1.65]).  
• The time to first asthma exacerbation was significantly longer for the Cinqair groups vs placebo in both studies.

Lung Function 
The effect of Cinqair 3 mg/kg administered once every 4 weeks on FEV₁ over time relative to placebo was assessed in all 4 studies. 
FEV₁ was the primary endpoint in the 16-week lung function studies for Study III and Study IV. 

Study III also studied a lower dose, Cinqair 0.3 mg/kg, that produced significant but numerically smaller changes in FEV₁ and blood eosinophil reduction vs the 3 mg/kg dose. While 2 doses of Cinqair were studied, Cinqair 3 mg/kg is the only recommended dose. 

Study IV was the only study to test Cinqair 3 mg/kg in asthma patients unselected for blood eosinophils (measured 3 to 4 weeks prior to dosing).

Over 16 weeks, the mean change from baseline in FEV₁ (difference from Cinqair and placebo) was:

• 137mL (95% CI, 76-198) in Study I,
• 93mL (95% CI, 30-155) in Study II,
• 160mL (95% CI, 60-259) in Study III, and
• 76mL (95 % CI, −6, 158) in Study IV.

Improvements in FEV₁ were seen at 4 weeks after the first Cinqair dose for Studies I and II, and maintained through Week 52.

The Asthma Control Questionnaire-7 (ACQ-7) and Asthma Quality of Life Questionnaire (AQLQ) were both assessed in Studies I, II, and III. 
The responder rate for both measures was defined as an improvement in score of 0.5 or more as threshold over 16 weeks.

• For ACQ-7, the responder rate for those randomized to Cinqair vs. placebo was 69% vs. 65% for Study I, 70% vs. 58% for Study II, and 64% vs. 58% for Study III. 
• For AQLQ, the responder rate for those randomized to Cinqair vs. placebo was 66% vs. 58% for Study I, 67% vs. 55% for Study II, and 64% vs. 48% for Study III.