Remibrutinib offers rapid, sustained symptom relief in patients with CSU

Treatment with remibrutinib, an oral, highly selective Bruton’s tyrosine kinase inhibitor, led to rapid symptom improvement that lasted for 52 weeks in patients with chronic spontaneous urticaria (CSU), according to the pivotal phase III REMIX-1 and -2 studies presented at EADV 2024.

As early as week 1, patients who received remibrutinib achieved significant improvements in weekly Urticaria Activity Score (UAS7) compared with those treated with placebo in REMIX-1 (mean change from baseline [CFB], -11.3 percent vs -4 percent; p<0.001) and REMIX-2 (mean CFB, -11.3 percent vs -2.9 percent; p<0.001).

There was also a significantly higher percentage of patients on remibrutinib vs those on placebo who achieved well-controlled urticaria, as indicated by UAS7 score of ≤6 (UAS7≤6), at week 1 in both studies (12.6 percent vs 0.7 percent [REMIX-1] and 10.8 percent vs 0.7 percent [REMIX-2]; p=0.001 for both).

In addition, significantly more remibrutinib-treated patients were completely free of itching and hives (UAS7 score of 0 [UAS7=0]) as early as week 2 (16.8 percent vs 1.3 percent; [REMIX-1] and 15.5 percent vs 1.3 percent [REMIX-2]; p<0.001 for both) than the placebo-treated patients.

In both REMIX studies, significant improvements with remibrutinib were sustained through 52 weeks, particularly improvements in UAS7 and UAS7≤6 among patients who initially received and continued treatment with remibrutinib.

“[With these results,] remibrutinib has the potential to become a novel oral treatment option that provides fast and sustained symptom relief for patients with CSU inadequately controlled by H1-antihistamines,” said lead author Professor Ana Maria Giménez-Arnau from the Department of Dermatology at Hospital del Mar and Research Institute and Universitat Pompeu Fabra, Barcelona, Spain.

REMIX-1 and -2 cohorts consisted of 470 (mean age 45 years, 68.3 percent female) and 455 (mean age 41.7 years, 65.3 percent female) patients with CSU (mean UAS7 of 30.3 and 30, respectively). The median duration of CSU was 6.6 years in REMIX-1 and 5.2 years in REMIX-2. Participants were randomized 2:1 to receive remibrutinib 25 mg twice daily (n=313 [REMIX-1] and n=300 [REMIX-2]) or placebo (n=157 and n=155, respectively) for a 24-week double-blind treatment period, followed by a 28-week open-label treatment period. By week 24, all placebo recipients were transitioned to remibrutinib (placebo-remibrutinib group). [EADV 2024, abstract 5727]

Among placebo recipients who switched to remibrutinib, significant improvements in UAS7 were observed at 52 weeks (mean CFB, -23 percent [REMIX-1] and -22.4 percent [REMIX-2]), which were similar to the trend observed with those taking remibrutinib initially.

Moreover, 64.1 percent and 62.4 percent of placebo-remibrutinib recipients achieved UAS7≤6 and 42.7 percent and 42.2 percent achieved UAS7=0 at week 52 in both REMIX-1 and -2 studies, respectively. These results were also consistent with those observed in the remibrutinib group.

“Taken together, patients who transitioned to remibrutinib from placebo at week 24, achieved fast and sustained reductions in UAS7 until study end,” said Giménez-Arnau.

Pooled safety endpoints

In a pooled safety analysis of REMIX-1 and -2 studies, the rates of adverse events (AEs; 64.9 percent vs 64.7 percent), serious AEs (3.3 percent vs 2.3 percent), and treatment discontinuation due to AEs (2.8 percent vs 2.9 percent) were comparable between the remibrutinib and placebo arms during the double-blind treatment period.

Giménez-Arnau noted that exposure-adjusted incidence rates did not increase with long-term treatment up to week 52, and there were no serious AEs associated with the study drug.

“Remibrutinib showed favourable safety and tolerability up to 52 weeks across both REMIX studies,” said Giménez-Arnau.

“Overall, both phase III [REMIX-1 and -2] studies in patients with CSU inadequately controlled by H1-antihistamines showed fast improvement in UAS7 with remibrutinib as early as week 1, with continued improvement up to week 52 vs placebo,” concluded Giménez-Arnau.