Jason Hawkes, MD, MS

CSU Burden of Disease and Quality of Life

Videos

Panelists discuss how chronic spontaneous urticaria (CSU) significantly impacts patients’ quality of life through persistent itching, unpredictable flares, sleep disruption, emotional distress, and daily activity limitations, underscoring the need for effective disease control.

Overview of Remibrutinib Phase 3 Clinical Trials in CSU

Video content above is prompted by the following:

What is notable about the efficacy and safety data from the REMIX-1 and -2 studies for remibrutinib?

Significant change from baseline in UAS7 scores as early as week 1 and sustained through week 24, with similar trends for ISS7 and HSS7

Primary end point met of superiority in change from baseline in UAS7 and ISS7/HSS7 at week 12 compared to placebo

A higher proportion of patients with remibrutinib achieve UAS7 ≤ 6 and UAS7 = 0

There was additional data presented this year from the REMIX trials: long-term 52-week data. What new insights do this data reveal about remibrutinib?

At week 24, patients receiving placebo were transitioned to remibrutinib; responses with remibrutinib were observed as early as the first week after switching and were sustained until the end of the study (28 weeks of treatment)

Almost half of patients were completely free of itch and hives (UAS7 = 0) as assessed at week 52

What is the clinical utility of the measures used in these studies (UAS7, ISS7, HSS7), and what is considered clinically meaningful for patients?

Panelists discuss how remibrutinib demonstrated rapid and sustained efficacy in the REMIX-1 and -2 trials through significant improvements in disease activity scores (UAS7, ISS7, HSS7) starting at week 1 and maintained through 52 weeks, with nearly half of patients achieving complete symptom resolution (UAS7 = 0) by week 52, while maintaining a favorable safety profile throughout the study period.

Differentiating BTK Inhibition From Genetic BTK Deficiency

How does inhibition of the BTK mechanism differ from manifestations of genetic BTK deficiency (XLA)?

BTK signaling plays a role in B-cell development, and 

 mutation linked to XLA has been shown to affect immunoglobulin levels, making patients with XLA more susceptible to serious infections; remibrutinib did not affect total serum Ig levels or infection rates in CSU patients in phase 2b core and extension studies or in phase 3 studies

Panelists discuss how pharmacological Bruton tyrosine kinase (BTK) inhibition with agents like remibrutinib appears safer than genetic BTK deficiency (X-linked agammaglobulinemia [XLA]), as clinical studies show the drug doesn't significantly impact immunoglobulin levels or infection rates in patients with chronic spontaneous urticaria (CSU), unlike the severe immunodeficiency seen in XLA.

Overview of BTK Inhibitors in Development for CSU Treatment

Let’s talk a bit about the BTK inhibitors currently being developed and studied for the treatment of CSU:

Remibrutinib: phase 3 trials, with 12-, 24-, and 52-week data available; inhibits BTK in mast cells, basophils, and B cells

Rilzabrutinib: currently in phase 2 trials

How do the BTK inhibitors under development for CSU treatment differ from earlier generations of BTK inhibitors used in oncology and other autoimmune diseases?

Older BTK inhibitors have limited selectivity and irreversibly inhibit additional kinases, increasing potential for off-target adverse effects (AEs; bleeding effects, cardiotoxicity [hypertension, atrial fibrillation], gastrointestinal effects, and rash).

Remibrutinib binds to the inactive conformation of BTK and shows higher selectivity, limiting the potential for these off-target AEs

Panelists discuss how newer Bruton tyrosine kinase (BTK) inhibitors being developed for chronic spontaneous urticaria (CSU), particularly remibrutinib (in phase 3 trials) and rilzabrutinib (in phase 2), are designed to be more selective than earlier oncology-focused BTK inhibitors, potentially reducing off-target effects like bleeding, cardiovascular complications, and GI issues.

Jason Hawkes, MD, MS

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