Regulatory filing for Dupixent for COPD in US expected by year’s end
Therapy shown to reduce COPD exacerbations by 34% in 2nd clinical trial
Treatment with Dupixent (dupilumab) — approved in the U.S. for five inflammatory conditions, to date — once again resulted in significantly fewer exacerbations, or periods of sudden symptom worsening, among people with moderate to severe chronic obstructive pulmonary disease (COPD) in the second of two similarly designed Phase 3 clinical trials.
Dupixent use also resulted in better lung function for these COPD patients, per an interim analysis of the NOTUS study (NCT04456673), which is expected to conclude in 2024.
The positive findings were robust enough for them to be considered the result of a main analysis, according to the therapy’s developers Sanofi and Regeneron Pharmaceuticals. The companies expect to present detailed trial results at an upcoming scientific forum.
“This is the first and only time an investigational biologic in COPD has shown a significant and clinically meaningful reduction in exacerbations in two Phase 3 trials and we are pleased that we can potentially deliver Dupixent faster to patients in need where no new advancements have been identified in over a decade,” Naimish Patel, MD, head of global development, immunology, and inflammation at Sanofi, said in a joint company press release. A biologic therapy is one derived from living organisms.
The results confirmed those of the earlier, replicate Phase 3 BOREAS trial (NCT03930732), and “validate our belief that Dupixent has the potential to transform the treatment of moderate-to-severe COPD,” Patel added.
The companies plan to use data from both trials to support a filing, by the end of the year, with the U.S. Food and Drug Administration (FDA) to seek Dupixent’s approval for treating COPD.
New data from 2nd trial confirm ‘unprecedented’ results from 1st
Treatment with Dupixent led to a greater than one-third reduction, compared with a placebo, in the number of exacerbations experienced by patients in this second trial, according to George D. Yancopoulos, MD, PhD, president and CEO at Regeneron.
“We are highly encouraged by these remarkable results from NOTUS … confirming the unprecedented results from our first Phase 3 trial, BOREAS,” Yancopoulos said.
“We are working to submit these data rapidly to the FDA,” he added.
European regulators already are reviewing a similar application seeking the therapy’s approval — though that one includes only data from the BOREAS study, according to the companies.
Discussions with other regulatory authorities worldwide are ongoing, the release stated.
Dupixent is currently FDA-approved for five other inflammatory conditions, mainly affecting the skin or the respiratory system. All are related to type 2 inflammation, characterized by an elevation in the blood of a set of immune cells called eosinophils.
The therapy is an antibody that blocks signaling molecules believed to drive type 2 inflammation, which also is implicated in COPD. About 300,000 people in the U.S. are estimated to live with uncontrolled COPD and evidence of type 2 inflammation, according to Dupixent’s developers.
The companies believe that by suppressing those inflammatory responses, the therapy may help to lessen respiratory symptoms in this subgroup of COPD patients.
We are highly encouraged by these remarkable results from NOTUS … confirming the unprecedented results from our first Phase 3 trial, BOREAS.
Dupixent holds FDA’s breakthrough therapy status as an add-on treatment for people with uncontrolled COPD and type 2 inflammation. That designation is intended to help speed its regulatory development.
BOREAS and its replicate trial, NOTUS, followed a similar study design. BOREAS enrolled 939 participants, ages 40-80, while NOTUS involved 935 participants, ages 40-85. Each of the participants had moderate to severe COPD and evidence of type 2 inflammation.
All patients also were current or former smokers with uncontrolled disease while on maximal standard-of-care inhaled therapy. Such treatment consists of corticosteroids, long-acting beta agonists, and long-acting muscarinic antagonists.
In both trials, participants were randomly assigned to receive a subcutaneous or under-the-skin injection of either Dupixent or a placebo, every two weeks, on top of standard triple therapy.
Dupixent meets all goals in both COPD trials, with benefits up to 1 year
The main goal of both studies was to evaluate changes in the frequency of COPD exacerbations over a year of treatment. Changes in lung function after 12 weeks, or about three months, and at one year were key secondary goals.
The newly reported results indicated that, similarly to the previously published BOREAS findings, NOTUS met all of these goals in trial.
Specifically, Dupixent led to a significant, 34% reduction in exacerbations compared with a placebo after a year. Moreover, the therapy significantly improved lung function relative to a placebo after three months of treatment, with the benefits sustained up to a year.
Safety findings were generally consistent with the known safety profile of Dupixent. Side effects more commonly reported in patients treated with Dupixent in the NOTUS trial included COVID-19 infection (9.4% vs. 8.2%), common cold (6.2% vs. 5.2%), and headache (7.5% vs. 6.5%).
The frequency of side effects leading to death was 2.6% in the Dupixent group and 1.5% in the placebo group.
“These results demonstrate the important role of type 2 inflammation in yet another chronic and debilitating disease, and the ability of Dupixent to address this inflammation,” Yancopoulos said.
In BOREAS, Dupixent was linked to a significant, 30% drop in exacerbations relative to a placebo after a year, and significant lung function improvements as early as two weeks. Patients given the therapy also experienced improvements in quality of life and less severe respiratory symptoms.
Side effects more common with Dupixent in this trial included headache, diarrhea, and back pain.
Meanwhile, the companies also are advancing the clinical program of another antibody-based treatment for COPD. Called itepekimab, that therapy now is being tested in moderate to severe COPD patients within two global, similarly designed Phase 3 trials: AERIFY-1 (NCT04701983) and AERIFY-2 (NCT04751487). Both are still recruiting. Data from that program are expected in 2025.
“We are not stopping with Dupixent,” Patel said.
“If positive, Dupixent and itepekimab could emerge as treatments for approximately 80% of those suffering from moderate-to-severe COPD with recurrent exacerbations,” Patel said.