Novel BTK Inhibitor for Chronic Hives Wins in Phase III Trial

ANAHEIM, Calif. — Treatment with remibrutinib, an investigational Bruton’s tyrosine kinase (BTK) inhibitor, led to fast improvement in symptom control for patients with chronic spontaneous urticaria (CSU) inadequately controlled by antihistamines, results from the phase III REMIX-1 and -2 studies showed.

At 12 weeks, the least-squares mean change in weekly Urticaria Activity Scores (UAS7) from baseline was -20.1 with the highly selective oral BTK inhibitor compared with -13.8 with placebo in the REMIX-1 study, and -19.6 versus -11.7, respectively, in the REMIX-2 study (P<0.001 for both), reported Sarbjit Saini, MD, of Johns Hopkins Asthma and Allergy Center in Baltimore.

Changes in UAS7 were apparent within the first 2 weeks of beginning treatment, Saini noted during the American College of Allergy, Asthma & Immunology annual meeting.

A complete response, or a UAS7 score of 0, was observed in 31.1% of remibrutinib patients in REMIX-1 and 27.9% in REMIX-2 compared with 11.1% and 6.5% of placebo patients, respectively (P<0.001 for both).

Despite treatment with second-generation H1 antihistamines, more than 50% of patients with CSU experience inadequate disease control, Saini said. “Remibrutinib has the potential to become a novel treatment option that may address unmet needs of patients with CSU currently inadequately controlled by antihistamines.”

Across both studies, significantly more remibrutinib patients achieved well-controlled disease compared with patients receiving placebo. “Roughly a third of patients in the studies achieved a reduction to a UAS7 less than 6 at the 2-week mark, and this effect was sustained during the first 12 weeks of study, rising to roughly about 50% of individuals across both studies,” Saini noted.

Remibrutinib also demonstrated superiority over placebo in regards to changes from baseline in weekly Itch Severity Score (ISS7) and weekly Hives Severity Score (HSS7) at 12 weeks:

• ISS7 scores: -9.6 vs -6.9 in REMIX-1 and -9.0 vs -5.7 in REMIX-2
• HSS7 scores: -10.5 vs -6.9 and -10.5 vs -6.0, respectively

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

In REMIX-1, mean age was 45, and 68.3% 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 was 41.7, and 65.3% were women. Mean UAS7 at baseline was 30, mean ISS7 was 14.2, and mean HSS7 was 15.8.

Between the two studies, adverse events, including respiratory tract infections, headache, and petechiae, occurred in 64% of patients in the remibrutinib groups and 64.7% of those in the placebo groups. Serious adverse events were reported in 3.3% of remibrutinib patients and 2.3% of placebo patients.

Liver transaminase (alanine and aspartate aminotransferase) elevations occurred in 1.3% of both groups during the study period, but Saini noted that they were “asymptomatic, transient, and reversible.”

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