In patients with chronic rhinosinusitis with nasal polyps, add-on mepolizumab (Nucala) reduced both polyp size and the need for surgery in the SYNAPSE study, a researcher reported.
In the 52-week, phase III, multicenter trial, treatment with the IL-5 inhibitor biologic was associated with a 57% reduction in the need for surgery versus placebo in patients with a history of one or more surgeries to reduce polyps, according to Claire Hopkins, MD, of King’s College London.
Mepolizumab added to standard-of-care treatments also met both study primary endpoints, showing statistically significant improvements in size of nasal polys and nasal obstruction versus placebo, she reported at the virtual European Respiratory Society (ERS) International Congress. The presentation of the SYNAPSE study findings was one of several discussions addressing the growing role of biologic therapies in the treatment of nasal polyps at ERS.
Mepolizumab is approved in the U.S. as add-on maintenance therapy for severe asthma with an eosinophilic phenotype in adults and children ages 6 years and up.
Based on the SYNAPSE findings, drugmaker GlaxoSmithKline said it would pursue regulatory approval for the drug as add-on therapy for nasal polyps.
In June 2019, the IL-4 inhibitor dupilumab (Dupixent) became the first FDA-approved treatment for poorly controlled chronic rhinosinusitis with nasal polyps.
SYNAPSE was conducted to examine the efficacy and safety of 4-weekly injections of 100 mg of mepolizumab in the treatment of adults with chronic rhinosinusitis and nasal polyps considered to be candidates for repeat surgery.
Hopkins noted that chronic rhinosinusitis with nasal polyps is an inflammatory condition that affects approximately 4% of adults, and has a significant impact on quality of life.
Current standard-of-care therapies for chronic rhinosinusitis and nasal polyps include intranasal corticosteroids, saline irrigation, short-term oral steroids, and surgery.
“Unfortunately, the benefits from these treatments is often short-lived, recurrences are common, and many patients have ongoing inadequate control of symptoms,” she said. “Type 2 inflammation plays a very central role in the pathophysiology of nasal polyps and treatment of type 2 inflammation has shown promise.”
In an earlier trial involving a 750-mg intravenous dosage of mepolizumab given every 4 weeks for a total of six doses, treatment was associated with reductions in nasal polyp size, improved symptoms, and reduced need for nasal surgery.
In SYNAPSE, patients were treated with 100-mg subcutaneous infusions of the IL-5 inhibitor, given once a week for 4 weeks in addition to standard care.
All patients recruited for the trial were non-smokers or former smokers, were biologic- and immunosuppressant treatment-naive, had nasal obstruction visual analog scale (VAS) scores of 5 or greater, and were judged to be in need of repeat polyp surgery.
Changes in total endoscopic nasal polyp score at week 52 and nasal obstruction VAS score at weeks 49 to 52 were the study’s primary endpoints. Secondary endpoints included time to nasal polyp surgery during the study, overall VAS symptom score, Sinonasal Outcome Test-22 score, systemic corticosteroid (SCS) use, composite and loss of smell VAS scores.
The authors reported that total endoscopic nasal polyp score and nasal obstruction VAS score significantly improved (P<0.001) with mepolizumab (n=206) versus placebo (n=201).
Median change in endoscopic nasal polyp score showed a 1-point improvement with mepolizumab (adjusted -0.73, 95% CI -1.11 to -0.34), while median change in nasal obstruction VAS score showed a >3-point improvement (adjusted -3.14, 95% CI -4.09 to -2.18).
Mepolizumab reduced nasal polyp surgery by 57% (hazard ratio 0.43, 95% CI 0.25-0.76, P=0.003), improved SNOT-22, VAS (overall, composite, loss of smell), and systemic corticosteroid use.
Data from the SINUS-52 trial of dupilumab also were presented in an ERS poster. The trial was conducted to examine the impact of dupilumab on blood and nasal type 2 inflammatory biomarkers in patients with chronic rhinosinusitis with nasal polyps, with and without comorbid asthma.
The study found that consistent with the drug’s mechanism of action, dupilumab reduced both blood and nasal secretion biomarkers of type 2 inflammation in these patients.
In an ERS session sponsored by drugmaker Novartis, Philippe Gevaert, MD, PhD, of Ghent University in Belgium, presented an overview of the data evaluating anti-IgE biologic therapies as add-on therapies for the treatment of nasal polyps.
Novartis’ anti-IgE drug omalizumab (Xolair) won European approval in August as add-on therapy for adults with poorly controlled severe chronic rhinosinusitis and nasal polyps.
“We know now that biologicals can play a role in the treatment of nasal polyps, and I think this is a big step forward for patients,” Gevaert said. “Before we had to do surgery after surgery after surgery and now we have a better option, and that is to treat patients with biologicals.”
Last Updated September 10, 2020
Disclosures
The SYNAPSE study was funded by GlaxoSmithKline (GSK).
Hopkins disclosed relevant relationships with Sanofi, AstraZeneca, Olympus, Smith, and Nephew.
Gevaert disclosed relevant relationships with, and/or support from 3NT, Ablynx, ALK, Argenx, Bekaert Textiles, Genentech, GSK, Hall Allergy, Medtronic, Novartis, Regeneron, Roche, Sanofi-Genzyme, Teva, and Thermo Fisher.