In August of 2023, Novartis announced positive top-line results from the phase 3 trials known as REMIX-1 and REMIX-2, which assessed remibrutinib 25 mg b.i.d., an inhibitor of Bruton’s tyrosine kinase (BTK), in those with diagnoses of chronic spontaneous urticaria (CSU) and with symptoms not adequately managed through H1-antihistamines.¹

Both phase 3 studies successfully achieved their primary goal of assessing the absolute change from baseline in the weekly urticaria activity score (UAS7) at 12 weeks, indicating substantial improvements in disease activity that are both clinically meaningful and statistically significant. The trials are also set to continue until the 52-week mark.

The investigators noted that remibrutinib also showed rapid onset of action in their study, a finding which was apparent due to the improvement in UAS7 occurring as early as 2 weeks in both the REMIX-1 and REMIX-2 trials.

“These positive top-line results from the Phase III REMIX studies confirm that remibrutinib, a highly selective BTK inhibitor, has the potential to be a first-in-class, oral treatment for people living with CSU whose symptoms are refractory despite use of antihistamines.” Shreeram Aradhye, MD, Novartis's President of Global Drug Development and Chief Medical Officer said in a statement.

Prior studies in phase 2 have shown that remibrutinib can exhibit both rapid onset of action and sustained efficacy among those struggling with moderate-to-severe CSU. The phase 2 trials had suggested favorable tolerability across various types of doses, and this research has now been corroborated by the new REMIX results.

If the drug were to receive approval, it could potentially serve as an oral therapeutic option to complement omalizuma, a singular injectable biologic known to be authorized for treatment of CSU.

Both of the new REMIX-1 and REMIX-2 studies have in common an identical design and have been done globally across multiple centers. These randomized, parallel-group, double-blind, placebo-controlled studies cover a count of 470 participants in REMIX-1 and 455 in REMIX-2.

The 2 studies are strategically made to determine the safety, efficacy, and the tolerance of remibrutinib among adult patients with inadequately-controlled CSU resistant to second-generation H1-antihistamines, comparing their results with those of a placebo arm.

The studies’ primary endpoints included the absolute alteration from baseline in the weekly score of urticaria activity, coupled with the absolute modification of score in itch and hive severity at the 12 week mark. Those participants currently included in both trials are allowed the opportunity to continue their treatment through to 52 weeks and continue participation in an extended long-term trial.

Officials with Novartis noted that CSU is known to affect an estimated 40 million people across the world, with the disease being characterized by abrupt cases of itchy hives and/or angioedema for a time of over 6 weeks. Most commonly, the disease affects those in the age bracket of 20 - 40, with females being known to experience it almost twice as much as men.^2,3

“CSU is a distressing and unpredictable disease, and patients urgently need effective, convenient and well-tolerated treatments that can provide rapid and sustained relief from the relentless itching and deep tissue swelling that greatly impact their daily lives,” Aradhye said in a statement.

References

1. ^{Novartis remibrutinib Phase III trials met their primary endpoints and showed rapid symptom control in chronic spontaneous urticaria. Published August 9, 2023. Accessed August 9, 2023. https://www.novartis.com/news/media-releases/novartis-remibrutinib-phase-iii-trials-met-their-primary-endpoints-and-showed-rapid-symptom-control-chronic-spontaneous-urticaria.}
2. ^{The World Bank. Population, total. Available at: https://data.worldbank.org/indicator/SP.POP.TOTL [Last accessed: August 2023].}
3. ^{Maurer M, Weller K, Bindslev-Jensen C, et al. Unmet clinical needs in chronic spontaneous urticaria. A GA2LEN task force report. Allergy. 2011;66:317–330.}