Sanofi and Regeneron reported promising results from a pair of pivotal phase 3 trials for the investigative add-on therapy.
New results from a pair of phase 3 studies have shown that dupilumab (Dupixent) significantly reduces exacerbations in patients with uncontrolled asthma while also improving lung function and independence from oral corticosteroids (OCS).
Results from the studies (QUEST, VENTURE) were presented at the 2018 American Thoracic Society (ATS) International Conference in San Diego, CA, this week, by Dupixent manufacturers Sanofi and Regeneron.
Dupilumab is currently approved in the US for the treatment of adults with moderate-to-severe atopic dermatitis, whose disease is not properly controlled with topical prescription medications. It is now being investigated as an add-on maintenance therapy for adults and adolescents with uncontrolled moderate-to-severe asthma, with a US Food and Drug Administration (FDA) action target date of October 20, 2018. Its case should be bolstered by the results of QUEST and VENTURE, in which the therapy reported significant improvements in key primary and secondary endpoints across patient populations.
The most notable successes were found in patients with severe Type 2 inflammatory asthma, a population characterized by elevated blood eosinophils, exhaled nitric oxide levels, and Immunoglobulin E (IgE).
The QUEST trial enrolled 1902 patients across the world, with 1795 (94%) adults and 107 (6%) adolescent patients. Patients were randomized to receive either 400 mg loading dose plus 200 mg every other week (n= 631); 600 mg loading dose and 300 mg every other week (n= 633), or 2 similar dose regimens of placebo (n= 317; 321). All patients also continued an inhaled corticosteroid (ICS) and up to 2 additional controller therapies through the 52-week study.
Researchers reported that 48% of patients given routine 200 mg dupilumab and 46% of patients given routine 300 mg dupilumab reported placebo-adjusted reductions for annualized rate of severe asthma exacerbations at study’s end (P < 0.001). In patients with at least 300 eosinophils/mL, 66% of those given 200 mg and 67% of those given 300 mg reported reductions (P < 0.001).
The 2 treatment groups also reported a 9% change in forced expiratory volume at 1 second (FEV1) from baseline to week 12. The lung function improvement was even greater in patients with significantly high eosinophil levels; the 200 mg and 300 mg patient groups reported 13% and 18% improvements, respectively.
The 52-week treatment period resulted in adverse event rates similar across all treatment groups (81% in combined dupilumab patients; 83% in combined placebo patients). The most frequently reported events in dupilumab patients were injection site reactions (17%), back pain (4%), and eosinophilia (4%).
Similar to the QUEST Trial, VENTURE researchers did not require a minimum biomarker level for patient enrollment. The 24-week study enrolled 210 patients with severe asthma to either dupilumab (103; 49%) or placebo (107; 51%). All patients regular used maintenance OCS in the 6 months prior to study enrollment. Dupilumab patients were administered a 600 mg loading dose and 300 mg every other week. Patients continued high-dose ICS and up to 2 controller therapies.
Researchers gauged for dupilumab’s aid in reducing OCS use for patients with severe asthma. It succeeded, as patients reported a 70% reduction in OCS dosing at week 24 (P < 0.001). Reduction was significant across most of the patient population — 80% of treated patients reported an OCS reduction of 50% or more, and 69% reduced their OCS dose to less than 5 mg daily (P < 0.001).
Researchers noted that 80% of the dupilumab patient population with significant eosinophil levels reported OCS dose reduction at 24 weeks. Just 42% of overall patients administered placebo reduced their OCS dosing.
Adverse events were similar across the treatment groups at week 24 (62% of dupilumab patients; 64.5% of placebo patients). However, a greater rate of dupilumab patients reported serious adverse events (9% versus 6%) — the most frequent of which were eosinophilia (14%), injection site reaction (9%), bronchitis (7%), and sinusitis (7%).
As an inhibitor to the IL-4/IL-3 pathway — an emerging driver of Type 2 allergic inflammation in patients with asthma or other atopic disease — dupilumab is showing capabilities as an add-on therapy to reduce both uncontrolled symptoms and patient treatment loads.
Its effects are a much-needed service for asthma care, as approximately 20% of patients have uncontrolled moderate-to-severe symptoms in spite of current treatment, Mario Castro, MD, professor of pulmonary and critical care medicine at Washington University School of Medicine, said in a statement.
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