Efficacy, safety, and pharmacokinetics of pumecitinib nasal spray for moderate-to-severe seasonal allergic rhinitis: a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial.

Background: Seasonal allergic rhinitis (SAR) is a pollen-triggered condition causing nasal inflammation and quality of life impairment. Pumecitinib, a topical Janus kinase (JAK) inhibitor may modulate allergic inflammation. We evaluated the efficacy, safety, and pharmacokinetics of pumecitinib nasal spray administered over a 14-day period during the pollen season in patients with moderate-to-severe seasonal allergic rhinitis (SAR). Methods: This phase 2, randomised, double-blind, placebo-controlled, parallel-group study was carried out at 20 centres in China. Adults aged 18-65 years with moderate-to-severe SAR were randomised 1:1:1:1 to receive placebo or pumecitinib nasal spray at doses of 0·2 mg, 1·2 mg, or 2·0 mg administered twice daily for 14 days. The primary efficacy endpoint was the mean change from baseline in daily reflective total nasal symptom score (rTNSS) over 14 days. The secondary endpoints included reflective total ocular symptoms (rTOSS), individual nasal and ocular symptoms, and rhinoconjunctivitis quality of life questionnaire (RQLQ) scores This study is registered with chitr.org.cn, ChiCTR2400081767, and is completed. Findings: Between March 20 and June 5, 2024, 169 patients were randomly assigned and 168 received treatment (92 male, 76 female) and were included in the full analysis set. Both the 1·2 mg and 2·0 mg doses of pumecitinib demonstrated significant improvements compared with placebo in the mean change from baseline in the daily rTNSS over 14 days (least-squares [LS] mean difference -1·2 [95% CI -2·2 to -0·2], p = 0·021, and -1·2 [-2·2 to -0·2], p = 0·018, respectively). These two dosage groups significantly improved rTOSS, individual nasal and ocular symptoms, and RQLQ scores compared to the placebo group. Treatment-emergent adverse events (TEAEs) occurred in 15% (0·2 mg), 33% (1·2 mg), 21% (2·0 mg), and 24% (placebo) of patients; most were mild, with no clear dose-response relationship. Interpretation: Pumecitinib 1·2 mg and 2·0 mg twice daily significantly alleviated nasal and ocular symptoms and improved quality of life in moderate-to-severe SAR, with a favourable safety profile during 14-day treatment. This provides proof of concept for topical JAK inhibition in SAR, warranting larger trials. Funding: PrimeGenX Therapeutics Co., Ltd.