Regeneron and Sanofi released more positive phase 3 trial results, a day following phase 2b results were shared at CHEST.
A phase 3 study has returned results that indicate dupilumab consistently treats asthma attacks and lung function in a wide variation of asthma patients.
The monoclonal antibody approved and marketed as Dupixent to treat moderate-to-severe atopic dermatitis was tested for adult and adolescent patients with severe, steroid-dependent asthma in the VENTURE trial. When combined to standard asthma therapies, the treatment showed a 70% patient reduction in oral corticosteroid (OCS) use at 24 weeks, versus 42% in a placebo treatment population.
Dupilumab also showed efficacy in asthma patients with Type 2 (T2) biomarkers such as raised blood eosinpphil levels. In patients with baseline eosinophil counts of at least 300 cells/microliter, the combination of dupilumab to therapies significantly reduced OCS use by an average of 80%, versus 43% in the placebo population.
Even with the marked OCS therapy reduction, the dupilumab patient group experienced 59% fewer exacerbations at week 24. The high-eosinophil count group experienced 71% fewer exacerbations.
Lung function improved in patients as well. At week 24, dupilumab improved forced expiratory volume over one second (FEV1) by an average of 15% (220ml) in the overall treatment group. The high-eosinophil count group improved by an average of 25% (320ml).
George D. Yancopoulos, MD, PhD, President and Chief Scientific Officer of Regeneron, said dupilumab has shown efficacy in asthma patients with T2 inflammation due to its ability to block the IL-4/IL-13 pathway.
“This is the third study in which dupilumab has demonstrated a reduction in asthma attacks and improvement in lung function in a broad group of patients with uncontrolled asthma — this effect was most profound in patients with elevated markers of Type 2 allergic inflammation, such as an eosinophil count over 300,” Yancopoulos said.
Dupilumab’s capability of improving FEV1 and reducing exacerbations was a topic of discussion at the 2017 Annual CHEST Meeting in Toronto, ON, CA. Lead study author Jonathan Corren, MD, discussed the results of the antibody’s phase 2b trial involving adult patients with uncontrolled persistent asthma for at least 1 year at baseline.
Along with FEV1 markers indicating T2 inflammation, the patients were also required to be on a stable treatment of fluticasone propionate (ICS) plus a long-acting beta antagonist (LABA) for at least a month, and have had at least 1 exacerbation in the year prior to baseline.
The study accumulated 846 patients to split into 5 treatment groups: dupilumab 200mg every 2 weeks, and every 4 weeks; dupilumab 300mg every 2 weeks, and every 4 weeks; and placebo. All therapy groups continued ICS plus LABA therapy, with the clinical treatment serving as an add-on.
A majority of patients (54.9%) had suffered at least 1 exacerbation in the year leading up to baseline. Just a small portion (7%) had experienced up to 4 exacerbations in that span. Researchers gauged patient quality of life (QoL) by exacerbation rates, as gauged in the 5-item Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ), Corren said.
At week 24, an estimated annualized severe exacerbation event rate showed the 4 dupilimab combination dosing regimens had a significant effect on QoL versus placebo. The most significant difference was in the rare patient group to have experienced 4 or more exacerbations in the past year. That patient group, taking dupilumab 200mg/300mg every 2 weeks, reduced estimated exacerbations by at least 80% versus placebo.
Patients showed similar ACQ and AQLQ score improvements at study’s end. The 2-week dupilumab therapy groups improved overall asthma control and QoL in all exacerbation subgroups, Corren noted.
The study concluded that Dupilumab 200mg and 300mg doses every 2 weeks may prove beneficial for uncontrolled, persistent asthma patients with a history of exacerbations. The positive results, combined with those of the previous phase 3 QUEST study and the VENTURE trial, have given companies Regeneron Pharmaceuticals and Sanofi enough safety and efficacy data to submit for a Supplemental Biologics Application (sBLA) to the US Food and Drug Administration (FDA) by the end of the year.
The phase 2b study, "Dupilumab Improves Asthma Control and Asthma-Related Quality of Life in Uncontrolled Persistent Asthma Patients Across All Baseline Exacerbation Rates," was published online in the CHEST Journal.
A press release for the VENTURE trial was made available.