Dupilumab Shows Promise in Phase 3 Trials Against CRSwNP

Claus Bachert, MD, PhD

New insight into how dupilumab treats symptoms of chronic rhinosinusitis with nasal polyps(CRSwNP) points to the potential of the commonly used drug.

A team, led by Claus Bachert, MD, PhD, Ghent University, presented a post hoc analysis exploring the effect of dupilumab across different responder definitions in objective and patient-reported endpoints in a pair of studies testing the efficacy and safety of dupilumab on patients with CRSwNP.

The data was presented at the American Academy of Allergy, Asthma & Immunology (AAAAI) 2021 Annual Meeting.

In previous studies, researchers have found dupilumab provided a reduction in nasal polyp score (NPS), as well as individual symptom scores in patients with severe CRSwNP. However, researchers have not conducted a combined responder analysis using these endpoints.

The Disease

CRSwNP is an inflammatory disease that impacts the nasal cavity and paranasal sinuses by displaying a predominantly type 2 inflammatory pathophysiology. This condition is associated with a high symptom burden, including nasal congestion, obstruction, loss of sense of smell, and rhinorrhea, as well as a poor health-related quality of life.

Current treatment includes intranasal corticosteroids, systemic corticosteroids, or sinus surgery. However, these options often fail to provide adequate symptom control, with high rates of nasal polyp recurrence and incomplete resolution of loss of sense of smell following surgery.

Previous Trials

In a pair of phase 3 trials—SINUS-24 and SINUS-52—the researchers added dupilumab to standard care and found significant improvement in endoscopic and radiologic outcomes and symptoms when compared to placebo for patients with severe CRSwNP.

However, in the responder analysis, they found even further improvement in both objective and patient-reported endpoints not previous disclosed.

In SINUS-24, patients were randomized to receive either dupilumab 300 mg subcutaneously every 2 weeks or a placebo for 24 weeks. In the second study, patients received either dupilumab 300 mg every 2 weeks until week 52, dupilumab 300 mg every 2 weeks until week 24, then every 4 weeks until week 52, or a placebo until week 52.

All patients used mometasone furoate nasal spray throughout the trials.

Responder Analysis

The investigators sought objective endpoints of nasal polyp scores and subjective endpoints of patient-reported daily symptoms of nasal congestion, loss of sense of smell, anterior rhinorrhea, and posterior rhinorrhea scores.

The researchers compared endpoints in the intention-to-treat population of dupilumab 300 mg or placebo, as well as for subgroups of patients with asthma, asthma and NSAID-ERD, prior surgery, systemic corticosteroid use within the previous 2 years.

Overall, dupilumab led to improvements compared to placebo across different responder definitions and thresholds, including objective and patient-reported endpoints in patients with severe CRSwNP, including individuals with asthma, NSAID-ERD, prior surgery, or corticosteroid use within the previous 2 years.

“A higher proportion of dupilumab patients versus placebo continued to demonstrate improvement in objective and patient-reported endpoints with more stringent responder criteria,” the authors wrote. “These data further demonstrate the broad spectrum treatment effect of dual IL-4 and IL-13 inhibition with dupilumab on symptoms of CRSwNP.”

Dupilumab

Dupilumab is a fully human VelocImmune-derived monoclonal antibody that blocks the shared receptor component for IL-4 and IL-13, both known as central drivers of type 2 inflammation in multiple diseases.

In 2018, the US Food and Drug Administration (FDA) approved dupilumab as an add-on maintenance therapy for adults and adolescents aged 12 years or older, with uncontrolled moderate-to-severe asthma with an eosinophilic phenotype or with oral corticosteroid-dependent asthma.

The study, “A Responder Analysis To Demonstrate Dupilumab Treatment Effect Across Objective and Patient-Reported Subjective Endpoints For Patients with Severe Chronic Rhinosinusitis with Nasal Polyps (CRSwNP),” was published online in AAAAI 21.