Remibrutinib improves CSU symptoms in phase III trials

Treatment with the investigational, oral Bruton’s tyrosine kinase (BTK) inhibitor remibrutinib improves symptoms in patients with chronic spontaneous urticaria (CSU) inadequately controlled on antihistamines, the phase III REMIX-1 and -2 studies have shown.

At 12 weeks, the least-squares mean change in weekly Urticaria Activity Scores (UAS7) from baseline was -20.1 with remibrutinib compared with -13.8 with placebo in the REMIX-1 study, and -19.6 vs -11.7, respectively, in the REMIX-2 study (p<0.001 for both). [ACAAI 2023, abstract LB001

“Changes in UAS7 were apparent within the first 2 weeks of treatment,” said Dr Sarbjit Saini from Johns Hopkins Asthma and Allergy Center in Baltimore, Maryland, US.

A UAS7 score of 0, suggestive of a complete response, was observed in 31.1 percent of patients treated with remibrutinib in REMIX-1 and 27.9 percent in REMIX-2. These were in comparison with  11.1 percent and 6.5 percent with placebo, respectively (p<0.001 for both).

Despite treatment with second-generation H1 antihistamines, more than half of patients with CSU experience inadequate disease control. Patients with CSU urgently need effective, convenient, and well-tolerated treatments that can provide rapid and sustained relief from relentless itching and deep tissue swelling.

A novel treatment option

“Remibrutinib, once approved, has the potential to become a novel treatment option that may address unmet needs of patients with CSU currently inadequately controlled on antihistamines,” said Saini.

Across both studies, more remibrutinib patients had their disease well-controlled compared with placebo. “Roughly a third of patients in the studies achieved a reduction of up to UAS7 <6 at the 2-week mark, and this effect was sustained during the first 12 weeks of the study, increasing to roughly about 50 percent of patients across both studies,” Saini reported.

As for changes from baseline in weekly Itch Severity Score (ISS7) and weekly Hives Severity Score (HSS7) at 12 weeks, remibrutinib was also better than placebo. ISS7 scores were -9.6 vs -6.9 in REMIX-1 and -9.0 vs -5.7 in REMIX-2, both in favour of remibrutinib. HSS7 scores were -10.5 vs -6.9 and -10.5 vs -6.0, respectively.

REMIX-1 and -2 population

A total of 470 participants were included in the REMIX-1 study and 455 in REMIX-2. They were randomized 2:1 to remibrutinib 25 mg twice daily or placebo.

Mean age of the patients was 45 years in REMIX-1 and 68.3 percent were women. Mean UAS7 at baseline was 30.4, mean ISS7 was 14.6, and mean HSS7 was 15.7.

In REMIX-2, mean age of the patients was 41.7, and 65.3 percent were women. Mean UAS7 at baseline was 30, mean ISS7 was 14.2, and mean HSS7 was 15.8.

In both studies, adverse events, including respiratory tract infections, headache, and petechiae, were comparable between groups (64 percent with remibrutinib vs 64.7 percent with placebo). Serious adverse events occurred in 3.3 percent of remibrutinib patients and 2.3 percent of placebo patients. Liver transaminase (alanine and aspartate aminotransferase) elevations occurred in 1.3 percent of both groups, but Saini considered those as asymptomatic, transient, and reversible.