New Long-Term Findings Confirm Safety, Efficacy of Oral Remibrutinib for CSU

New phase 3 data from the REMIX-1 and REMIX-2 trials suggest patients with chronic spontaneous urticaria (CSU) may see substantial and early relief of symptoms with remibrutinib, with sustained results observed up to 52 weeks among those reporting symptoms despite second-generation H1-antihistamine use.¹

These findings were announced by pharmaceutical company Novartis and highlight the potential use of remibrutinib, a selective Bruton’s tyrosine kinase (BTK) inhibitor, for treatment of CSU. The new data are being presented at the 2024 European Academy of Allergy and Clinical Immunology (EAACI) Congress in Spain.

“A large majority of people with CSU are living with uncontrolled and debilitating symptoms, often trying to manage the condition by cycling through antihistamines at higher doses with no lasting respite, impacting heavily on their day-to-day lives,” Martin Metz, professor of dermatology at the Universitätsmedizin Berlin in Germany, said in a statement. “Remibrutinib has become an important investigational treatment for CSU as it blocks the BTK cascade and inhibits the release of histamine.”

CSU is characterized by chronic hives which can last 6 or more weeks and impact around 40 million individuals around the world. Antihistamines are frequently prescribed by clinicians to block histamine receptors among CSU patients, reducing swelling and itching, but over half of those with CSU remain unable to adequately control their disease through H1-antihistamines alone.²

The investigational drug known as remibrutinib is a highly selective, covalent, oral BTK inhibitor which is designed to block the BTK pathway in CSU patients and thereby prevent histamine release. This is carried out to diminish the presence of the condition’s characteristic hives and swelling, and in combination with standard-dose antihistamines, the investigational treatment works to target the release of histamines as well as histamine receptors.

The aforementioned REMIX-1 and REMIX-2 phase 3 studies were designed identically and were multicenter, double-blind, global, randomized, placebo-controlled phase 3 studies which involved 470 and 455 subjects, respectively. The study’s investigators set out to assess the results of twice-daily treatment with 25 mg of remibrutinib among adults with CSU who were also inadequately treated with second-generation H1-antihistamines.

The studies’ main outcomes evaluated by their research teams included shifts from the point of baseline in subjects’ weekly urticaria activity score (UAS7), weekly itch severity score (ISS7), and weekly hive severity score (HSS7) at the 12-week mark. Those included as participants were given a stable dose of a second-generation H1-antihistamine throughout the team’s research.

Overall, remibrutinib was shown to have met all of the team’s primary endpoints for individuals with CSU who had been unresponsive to second-generation H1-antihistamines, with results having been consistent with earlier findings at the 12 and 24-week marks. These results included improvements in patients’ UAS7, ISS7, and HSS7 scores.³

The investigators noted that those who had been initially placed in the placebo arm of the study and were then switched to remibrutinib at the 24-week mark were found to have had rapid and sustained symptom improvements from the initial week after their switch. The team noted that close to half were able to get complete relief from hives and itch (UAS7=0) by the 52-week mark.

Treatment with remibrutinib was shown to be well-tolerated, with the research team noting that the safety profile had been comparable to that of placebo. They added that adverse events (AEs) and serious AEs had also been similar between the treatment and placebo arms of the study within the initial 24 weeks.

Common AEs in the REMIX studies included respiratory infections and headaches, all of which were comparable to placebo. Liver function tests remained balanced between groups, with any transaminase elevations being asymptomatic, temporary, and reversible. Investigators did not link any serious AEs to the study medication.

“These data show that remibrutinib has the potential to offer patients and physicians a well-tolerated oral treatment that provides early and lasting efficacy,” Metz concluded in his statement.¹

If approved by the US Food and Drug Administration (FDA), remibrutinib would represent a new oral treatment option for CSU treatment and function as an alternative to the injectable option omalizumab.

Outside of CSU treatment, the investigational drug is being assessed for use within other immune-mediated conditions such as chronic inducible urticaria, hidradenitis suppurativa (HS), food allergies, and multiple sclerosis. Novartis is slated to apply for global regulatory approval for remibrutinib as treatment for CSU beginning in the second half of 2024.¹

References

1. ^{Novartis Phase III data confirm sustained efficacy and long-term safety of oral remibrutinib in chronic spontaneous urticaria. Novartis. May 31, 2024. https://www.novartis.com/news/media-releases/novartis-phase-iii-data-confirm-sustained-efficacy-and-long-term-safety-oral-remibrutinib-chronic-spontaneous-urticaria. Date accessed: June 3, 2024.}
2. ^{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.}
3. ^{Metz M, Giménez-Arnau A, Hide M, et al. Long-term efficacy and safety of remibrutinib in patients with chronic spontaneous urticaria in the Phase 3 REMIX-1 and REMIX-2 studies. Presented as a late oral abstract session on clinical trials at EAACI 2024; May 31-June 3, 2024; Valencia, Spain.}