Additional results from an interim analysis of a pivotal phase 2b study of Dupilumab in adult patients with moderate-to-severe asthma who are uncontrolled despite treatment with inhaled corticosteroids and long-acting beta agonists ( ICS/LABA ).
The study met its primary endpoint of improving lung function in asthma patients with high blood eosinophils counts ( greater than or equal to 300 eosinophilic cells/microliter ).
Such high counts are thought to be a marker for patients more likely to have atopic or allergic asthma.
New data on secondary endpoints presented at the American Thoracic Society 2015 International Conference included results in study patients with low blood eosinophils ( less than 300 eosinophilic cells/microliter ) who are thought to be less likely to suffer from allergic asthma and thus less likely to respond to Th2 targeted therapies.
Dupilumab is an investigational therapy in clinical development that inhibits signaling of IL-4 and IL-13, two cytokines required for the Th2 ( or Type 2 ) immune response.
The new results focused on asthma patients with low eosinophil counts ( LEos, less than 300 eosinophilic cells/microliter ). In this population, patients treated with either 200 mg or 300 mg Q2W doses of Dupilumab showed an approximately 8% improvement in forced expiratory volume over one second ( FEV1, a standard measure of lung function ) at week 12 ( p less than 0.001 ), in comparison to placebo, both in combination with ICS/LABA.
Additionally, the 200 mg and 300 mg Q2W doses of Dupilumab in combination with ICS/LABA showed 68% and 62% reductions, respectively, in adjusted annualized rate of severe exacerbations in the LEos population ( p less than 0.01 and p less than 0.05 ), in comparison to placebo in combination with ICS/LABA.
These results are consistent with previously reported positive results in asthma patients with high eosinophils ( HEos, greater than or equal to 300 eosinophilic cells/microliter ) and the overall patient population, in which the two Q2W doses of Dupilumab in combination with ICS/LABA has demonstrated a statistically significant 12 to 15% improvement in FEV1 over placebo at week 12 and a 64 to 75% improvement in annualized rate of severe exacerbations over placebo.
Dupilumab has also significantly reduced mean fractional exhaled nitric oxide ( FeNO ) for both Q2W doses tested ( 200 and 300 mg ) and the three patient populations ( overall, LEos and HEos ), in a roughly dose-dependent manner.
FeNO is recommended by the American Thoracic Society clinical practice guidelines to assess airway inflammation, since higher than normal levels of nitric oxide may be released when a patient has a chronic airway disease, such as asthma.
The most common adverse event was injection site reaction, which was more frequent in the Dupilumab dose groups ( 13 to 25% ) compared to placebo ( 12% ).
Other common adverse events in the study included upper respiratory tract infection ( 10 to 13% Dupilumab; 13% placebo ), headache ( 5 to 10% Dupilumab; 8% placebo ), nasopharyngitis ( 3 to 10% Dupilumab; 6% placebo ) and bronchitis ( 5 to 8% Dupilumab; 8% placebo ).
The incidence of infections was balanced across treatment groups ( 42 to 45% Dupilumab; 46% placebo ), as was the incidence of serious adverse events ( 3 to 7% Dupilumab; 5% placebo ).
The double-blind, placebo-controlled, 24-week, dose-ranging study enrolled 776 adult patients with moderate-to-severe uncontrolled asthma, as defined by the Global Initiative for Asthma 2014 Guidelines.
Trial participants were randomized to receive one of four doses of Dupilumab ( 300 mg every other week, 200 mg every other week, 300 mg monthly, 200 mg monthly ) or placebo.
Approximately 42% of patients had high eosinophils across the dose groups.
During the treatment period, patients continued their stable medium- or high-dose inhaled corticosteroid and long-acting beta agonist ( ICS/LABA ) combination product.
A severe exacerbation event during the study was defined as a deterioration of asthma requiring the use of systemic corticosteroids for three or more days, or hospitalization or an emergency room visit. ( Xagena )
Source. Sanofi, 2015