Remibrutinib ‘very effective’ in treating moderate to severe chronic spontaneous urticaria
Click Here to Manage Email Alerts
Remibrutinib appeared very effective in treating moderate to severe chronic spontaneous urticaria, with a rapid onset of action and a favorable safety profile, according to a study published in The Journal of Allergy & Clinical Immunology.
These results indicate the drug’s potential as a preferred oral treatment option, Marcus Maurer, MD, PhD, professor of dermatology and allergy at Charité – Universitätsmedizin Berlin and associate director of the Allergie-Centrum-Charité in Berlin, and colleagues wrote.
“Chronic spontaneous urticaria (CSU) is a distressing and unpredictable disease, characterized by the occurrence of itchy wheals (hives), angioedema or both for 6 weeks or more, with no known cause, and can have a major negative impact on patients’ quality of life,” Angelika Jahreis, MD, PhD, FAAD, global head development unit immunology and clinical development excellence of Novartis, who was not an author on the study, told Healio.
“Moreover, despite existing treatments, approximately 60% of patients do not achieve complete control with first-line treatment antihistamines,” Jahreis continued.
Study findings
The randomized, double-blind phase 2b study included 311 patients aged 18 years and older (mean age, 45 years; 71.4% women) with moderately or more active CSU that was inadequately controlled with second-generation H1-antihistamines.
In addition to receiving a second-generation H1-antihistamine, researchers randomly assigned patients to 10 mg (n = 44), 35 mg (n = 44) or 100 mg (n = 47) of remibrutinib (LOU064, Novartis) once a day; 10 mg (n = 44), 25 mg (n = 44) or 100 mg (n = 45) twice a day; or placebo (n = 43) for 12 weeks.
Patients also recorded CSU signs and symptoms in an electronic Urticaria Patient Daily Diary, including a Urticaria Activity Score (UAS). Change in weekly UAS (UAS7) from baseline to week 4 and safety served as the study’s main endpoints.
According to the researchers, all the doses of remibrutinib significantly improved signs and symptoms of CSU compared with placebo.
Overall, there was a dose-response for remibrutinib in UAS7 change from baseline compared with placebo (max t-statistics = 6.67; P < .0001).
Also, all of the remibrutinib doses had statistically significant improvements in the least mean (LS) changes in UAS7 from baseline to week 4 compared with placebo, including –19.1 for the 10 mg and 35 mg daily doses, –14.7 for the 100 mg daily dose, –16 for the 10 mg twice daily dose, –20 for the 25 mg twice daily dose and –18.1 for the 100 mg twice daily dose, compared with –5.4 for placebo (nominal P < .001 for all doses vs. placebo).
These LS mean changes in UA7 representing clinical improvements were observed as early as week 1 and sustained through week 12 for all doses, with significant differences compared with placebo (P < .005).
Each individual remibrutinib dose group had a larger number of patients who achieved complete response to treatment, defined as a UAS7 score of 0, and well-controlled disease, defined as a UAS7 score of 6 or less, over time and through week 12 than the placebo group. The group receiving 25 mg twice a day showed the highest proportion of achieving UAS7 of 0 (41.9% vs. 14.3%) and UAS7 of 6 or less (55.8% vs. 28.6%) compared with the placebo group.
“The trial showed that all remibrutinib doses provided significant improvements in weekly urticaria activity score change from baseline at week 4 and week 12 compared to placebo, and a favorable safety profile across the entire dose range tested,” Jahreis said.
There was no apparent dose-dependent pattern in the safety profile, according to the researchers, and 58.1% of the patients reported at least one adverse event (mild, 38.6%; moderate, 16.9%; severe, 2.6%).
The most common adverse events included infections and infestations in the remibrutinib groups (24%) and in the placebo group (21.4%), followed by skin/subcutaneous tissue disorders in the remibrutinib group (16.9% ) and nervous system disorders in the placebo group (16.7%).
There were no deaths; 1.9% (n = 5) of the patients receiving remibrutinib experienced serious adverse events, three of which were not related to the treatment and two that were: flare or aggravation of CSU and renal abscess.
Implications
Based on these findings, the researchers said that remibrutinib demonstrated robust clinical efficacy, rapid onset of action and a favorable safety profile with a broad range of doses, indicating its potential as an oral treatment option for patients with moderate to severe CSU.
“These results provide evidence and support the potential of remibrutinib as a new oral treatment option for patients whose disease is not controlled by antihistamines,” Jahreis said.
Although it is currently an investigational product, Jahreis continued, remibrutinib is a highly selective Bruton tyrosine kinase (BTK) inhibitor with a favorable benefit/risk profile across the entire dose range tested in the study.
“If approved, remibrutinib will complement Xolair (omalizumab; Genentech, Novartis) as a therapy for CSU,” Jahreis continued. “Xolair remains an important medicine in our portfolio. It is the only approved biologic treatment designed to target and block lgE, a key driver of the inflammatory process in CSU.”
Next, the researchers will assess the drug’s longer-term efficacy, safety and tolerability in an ongoing 1-year study extension of adults with CSU with inadequate control via H1-antihistamine as well as in a phase 3 remibrutinib program that is now recruiting patients. Novartis expects results in 2024.
Perspective
Back to Top
These findings are indeed significant, as remibrutinib targets two pathways that are involved in CSU. Unfortunately, around 30% of patients with CSU do not respond to treatment with omalizumab, so there is an unmet need for new drugs. The effect of remibrutinib was rapid, in 1 week, which patients will highly appreciate.
Next, research should try to identify a biomarker that would identify which patients with CSU would be better suited for BTK inhibitors like remibrutinib vs. omalizumab.
In terms of safety, my initial concerns about the use of BTK inhibitors involved adverse effects, as high-dose BTK inhibitors raise concerns about adverse effects in treatments for lymphoma. Interestingly, in this trial, the lower doses of 10 mg and 35 mg actually had better efficacy than the 100 mg doses with a very good safety profile, suggesting that lower doses of remibrutinib will be efficacious for CSU.
Collapse
Read more about
Click Here to Manage Email Alerts