Stapokibart makes the grade in severe chronic rhinosinusitis with nasal polyps

In Asian patients with severe chronic rhinosinusitis with nasal polyps who are receiving daily intranasal corticosteroid, add-on treatment with the novel monoclonal antibody stapokibart helps shrink polyp size and bring down the severity of symptoms, as shown in the phase III CROWNS-2 study conducted in China.

At 24 weeks, nasal polyp score decreased by 2.6 points with stapokibart, surpassing the clinically meaningful 1-point reduction threshold. This change was also significantly greater compared with the 0.3-point reduction observed with placebo (least square [LS] mean difference, −2.3, 95 percent confidence interval [CI], −2.6 to −1.9; p<0.001). [JAMA 2025;doi:10.1001/jama.2025.12515]

For the co-primary endpoint for nasal congestion score, stapokibart yielded a reduction of 1.2 points, likewise meeting the clinically meaningful 0.5-point reduction threshold and outperforming placebo (–0.5 point; LS mean difference, −0.7, 95 percent CI, −0.9 to −0.5; p<0.001).

Results for several secondary efficacy endpoints also favoured stapokibart vs placebo. At week 24, stapokibart-treated patients were more likely to achieve a reduction in nasal polyp score of ≥1 (90.0 percent vs 38.2 percent) or ≥2 (81.1 percent vs 14.6 percent). They saw greater improvements in imaging-assessed sino-nasal inflammation (Lund-Mackay computed tomography score: LS mean difference, −8.0; p<0.001), overall nasal symptoms (total symptom score: LS mean difference, −2.2; p<0.001), sense of smell (University of Pennsylvania Smell Identification Test: LS mean difference, 7.5; p<0.001; loss-of-smell score: LS mean difference, −1.0; p<0.001), and quality of life (22-item Sino-Nasal Outcome Test score: LS mean difference, −12.1; p<0.001).

These findings may have important implications, given that severe uncontrolled chronic rhinosinusitis with nasal polyps accounts for about 40 percent of all cases of chronic rhinosinusitis with nasal polyps and impairs physical and mental health-related quality of life, according to CROWNS-2 investigators. [Allergy 2017;72:282-290; J Asthma Allergy 2023;16:323-332] 

“Many such patients also have coexisting asthma, which may be exacerbated by uncontrolled rhinosinusitis. Highly effective treatments are needed to address this condition,” they said. [J Allergy Clin Immunol Pract 2021;9:1133-1141]

CROWNS-2 included 179 adult patients (mean age 45 years, 34.1 percent women) with chronic rhinosinusitis with nasal polyps who had a history of systemic corticosteroid use or sinonasal surgery and a bilateral nasal polyp score of ≥5 (on a scale of 0–8) and a weekly mean nasal congestion score of ≥2 (on a scale of 0–3). The median disease duration was 6 years.

All patients were initiated on mometasone furoate nasal spray 100 µg, administered in each nostril daily for 4 weeks. Then, they were randomly assigned to receive additional treatment with either stapokibart 300 mg (n=90) or placebo (n=89), given subcutaneously every 2 weeks for 24 weeks. This was followed by a 28-week open-label phase wherein all patients received stapokibart.

Of the patients, 93 (52 percent) had previously received systemic corticosteroids, 114 (63.7 percent) had undergone nasal polyp surgery, and 89 (49.7 percent) had comorbid asthma. A total of 139 patients (77.7 percent) had eosinophilic chronic rhinosinusitis with nasal polyps, defined as having blood eosinophils of ≥6.9 percent (without asthma) or ≥3.7 percent (with asthma) or an eosinophil count of 55 per high-power field or greater or ≥27 percent in nasal polyp tissue.

Efficacy findings were consistent in the subgroup of patients with eosinophilia.

T2 pathway targeting

The monoclonal antibody stapokibart targets type 2 (T2) inflammation by binding IL-4Rα and has a similar mechanism of action to the biologic dupilumab. However, stapokibart has a unique binding epitope, as the investigators pointed out.

In a previous study, stapokibart was shown to reduce polyp size and sinus opacification and improve symptoms and quality of life in patients in China with severe eosinophilic chronic rhinosinusitis with nasal polyps. [EClinicalMedicine 2023;61:102076] Findings from CROWNS-2 confirm the efficacy of stapokibart in patients with eosinophilia and show that the drug helps improve outcomes in the overall population of patients with severe uncontrolled chronic rhinosinusitis with nasal polyps.

However, the investigators acknowledged that the sample size of the subgroup of patients without eosinophilic disease was small. “Consequently, statistical power to confirm stapokibart’s therapeutic effect in this specific population was insufficient, and the efficacy of stapokibart in noneosinophilic chronic rhinosinusitis with nasal polyps was not directly confirmed in this study.”

As for safety, “stapokibart was well tolerated over 52 weeks, with a low incidence of adverse events (AEs) and no serious treatment-related adverse events (TEAEs) that led to treatment discontinuation,” they said.

During the first 24 weeks of treatment, AEs occurred in 77.8 percent of patients with stapokibart and 69.7 percent with placebo. The most common AE was upper respiratory tract infection. Notably, more stapokibart-treated patients had arthralgia (7.8 percent vs 0 percent) and hyperuricemia (5.6 percent vs 1.1 percent). Serious AEs occurred in 2.2 percent and 1.1 percent of patients in the respective groups.