Long-term OLE boosts potential of remibrutinib for CSU

In the 52-week open-label extension (OLE) of a phase IIb study presented at AAAAI 2023, the BTK* inhibitor remibrutinib demonstrated sustained efficacy and a favourable safety profile for the treatment of chronic spontaneous urticaria (CSU).

“In the key efficacy analysis, remibrutinib 100 mg BID showed rapid and sustained improvement in UAS7**,” reported the research team led by Dr Warner Carr from the Allergy and Asthma Associates of Southern California, and Southern California Research, Mission Viejo, California, US.

At week 52, mean change from baseline in UAS7 was -21.8. This was sustained from the -19.4 score reported at week 12. Week 12 saw 43 percent of participants achieving UAS7=0. By week 52, this rate increased to 56 percent. [AAAAI 2023, Late Breaking Oral Abstract Session 3611]

In patients reporting ≥1 treatment-emergent adverse event (TEAE), about three-quarters had TEAEs, but these were mostly mild (35 percent) or moderate (32 percent). Only 3 percent had serious AEs.

“Two notable newly occurring liver enzyme increases were both isolated ALT*** >3x and <5x ULN^# with normal bilirubin levels, and both returned to normal levels during the study,” the researchers added.

The most common AEs were infections and infestations (31 percent) followed by skin and subcutaneous tissue disorders (27 percent). “The higher rate of grouped skin and subcutaneous tissue disorder events was driven by CSU events (11 percent),” they said.

Bleeding was an AE of special interest (AESI), with an incidence rate of 6 percent. This correlated with the rate observed in the core study, and all cases were minor in nature. Cytopenias, another AESI, were only observed in two participants and were mild in severity. “Cytopenias continued to be rare with long-term treatment and not correlated with infectious events,” they said.

This long-term OLE included those who completed the preceding core study, wherein participants received any of six doses of the active drug or placebo. Following a 12-week observation period, 194 patients (mean age 45.5 years, 72 percent female) who have achieved UAS7≥16 by week 12 or 16 of the core study entered the OLE phase. They were given remibrutinib 100 mg BID. A total of 156 completed the OLE.

Supports core study findings

There is an unmet need for new CSU treatments. BTK inhibition could be an attractive therapeutic alternative due to its pivotal role in FcεR1-mediated signalling of mast cells and basophils, and their relevance to the pathogenesis of CSU. [www.novartis.com/news/media-releases/novartis-data-show-rapid-and-effective-disease-activity-control-remibrutinib-lou064-patients-chronic-spontaneous-urticaria]

In a previous press release, Dr Angelika Jahreis, Novartis Global Head Development Unit Immunology, Hepatology & Dermatology, remarked that they were “excited to rapidly develop remibrutinib” – a novel, highly selective, potent, covalent oral BTK inhibitor – following the favourable outcomes in the core 12-week study. “The fast onset of control achieved with this novel oral agent in patients with previously inadequately controlled CSU is compelling.”

“[In the OLE,] remibrutinib showed fast and sustained efficacy for up to 52 weeks in patients with CSU who were inadequately controlled by H₁-antihistamines,” said Carr and colleagues. Remibrutinib also demonstrated a favourable safety and tolerability profile that aligned with that observed in the core study. [J Allergy Clin Immunol 2022;150:1498-1506.e2]

“[Together with the core findings, our results support] remibrutinib as a potential new oral treatment option for patients with CSU,” they concluded.

Phase III studies are underway to further ascertain the role of remibrutinib in the treatment of CSU, a distressing and unpredictable disorder that substantially impairs patients’ quality of life. [Allergy 2022;77:734-766]