Novartis' BTK Inhibitor Remibrutinib Nominated for Priority Review in China for Chronic Spontaneous Urticaria

Screenshot source: CDE official website

CSU refers to chronic urticaria that persists for 6 weeks or longer. The underlying cause of the disease is intrinsic factors rather than exposure to allergens or external triggers, and it is characterized by the sudden appearance of itchy wheals and/or deep tissue swelling (angioedema, which can occur on the face, throat, hands, and feet). This condition affects people of all ages but is most commonly seen in those aged 20–40, with the prevalence among women being almost twice that of men. CSU can cause significant emotional distress for patients; most experience sleep deprivation, and there is a high prevalence of mental disorders such as anxiety or depression, along with impaired work productivity. Antihistamines are commonly used to treat CSU because they block histamine receptors and prevent the pro-inflammatory effects of histamine, thereby alleviating itching and swelling. However, more than 50% of CSU patients do not achieve adequate control with H1-antihistamines alone.

Remibrutinib is an investigational, highly selective, covalently binding oral BTK inhibitor.Can block the BTK cascade reaction and inhibit histamine release, which leads to itchy wheals and swelling.When remiburutinib is used in combination with a standard dose of antihistamine, it targets two parts of the inflammatory pathway, producing a "two-pronged" effect. Remiburutinib inhibits histamine release, while antihistamines block histamine receptors, thereby alleviating CSU symptoms.

In June 2024, Novartis announced in the pivotal Phase 3 clinical trials REMIX-1 and REMIX-2 that forCSU patients with symptoms persisting after using second-generation H1-antihistaminesRemibrutinib significantly improved symptoms in the early stages of treatment and continued to do so until week 52. REMIX-1 and REMIX-2 are two identical global, multicenter, randomized, double-blind, parallel-group, placebo-controlled Phase III studies, with REMIX-1 enrolling 470 participants and REMIX-2 enrolling 455 participants.These two studies aim to investigate the efficacy, safety, and tolerability of remibrutinib (25mg, twice daily) compared to placebo in adult CSU patients who are inadequately controlled by second-generation H1 antihistamines.According toClinicalTrialsAccording to the clinical trial registration information on the official website, clinical research centers in China are involved in both studies.

The latest long-term Phase 3 REMIX-1 and REMIX-2 data evaluated at Week 52 show:

• Compared with placebo, the significant symptom improvement demonstrated by remibrutinib at week 12 persisted until week 24, specifically reflected inSignificant improvements in indicators such as the Weekly Urticaria Activity Score (UAS7), Weekly Itch Severity Score (ISS7), and Weekly Hives Count Score (HSS7)。

• Patients receiving placebo treatment were switched to remibrutinib treatment at Week 24;A treatment response to remibrutinib was observed in the first week after changing medication, and the effect persisted until the end of the study (28 weeks of treatment).。

• According to the evaluation results of Week 52, nearly half of the patients had no itching or urticaria symptoms at all (UAS7=0).

In the study, remibrutinib also demonstrated good tolerability and exhibited favorable and stable safety over 52 weeks of treatment, with liver function test results comparable to the placebo group. Moreover, long-term treatment did not increase the risk of treatment-related adverse events. The elevation of liver transaminases in the remibrutinib group was similar to that in the placebo group, asymptomatic, transient, and reversible. The researchers concluded that no serious adverse events related to the study drug occurred.

This innovative BTK inhibitor is proposed to be included in the priority review in China, which means that the product is expected to reach patients more quickly.