Novartis Submits NDA in China for Remibrutinib, a First-in-Class BTK Inhibitor for Chronic Spontaneous Urticaria

Feb 27, 2025 14:05 CST Updated 14:05

Novartis

Drug Development and Manufacturing

▎Edited by the WuXi AppTec content team

Today (February 27),The official website of the Center for Drug Evaluation (CDE) under the China National Medical Products Administration has just announced,Novartis' Application for a Class 1 New DrugRemibrutinib TabletsThe listing application has been accepted. According to publicly available information, this is a Novartis research and development project.BTK Inhibitor Remibrutinib. The first indication for this product is the treatment ofChronic Spontaneous Urticaria (CSU)The Phase 3 clinical trial for this indication has yielded positive results.The CSU symptoms of the patients improved as early as one week after receiving remibrutinib treatment and continued until 52 weeks. Notably, this is the first time that remibrutinib has been submitted for marketing worldwide.

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 between the ages of 20 and 40, with the prevalence in women being almost twice that of men. CSU can cause significant emotional distress for patients, with most experiencing sleep deprivation and a high incidence of mental disorders such as anxiety or depression, which also impacts work efficiency. 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 that in the pivotal Phase 3 clinical trials REMIX-1 and REMIX-2, remibrutinib significantly improved symptoms early in treatment and sustained the effect through Week 52 in CSU patients who still had symptoms after using second-generation H1-antihistamines. REMIX-1 and REMIX-2 are two identical global, multicenter, randomized, double-blind, parallel-group, placebo-controlled Phase 3 studies, with REMIX-1 enrolling 470 subjects and REMIX-2 enrolling 455 subjects.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 participated 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 improvement in symptoms exhibited 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 switching medications, 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 a favorable and stable safety profile 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 incidence of elevated liver transaminases was similar between the remibrutinib and placebo groups, being asymptomatic, transient, and reversible. Researchers concluded that no serious adverse events related to the study drug occurred.

Except for CSU, rResearch on the treatment of other immune-mediated inflammatory diseases with emibrutinib is also underway, such asHidradenitis Suppurativa, the drug met the primary endpoint in the Phase 2 study;Meanwhile, remibrutinib treatmentFood Allergy, Chronic Inducible Urticaria, and Multiple SclerosisResearch on diseases such as ... is also underway.

References:

[1] Official website of the Center for Drug Evaluation, National Medical Products Administration of China. Retrieved Feb 27, 2025, from https://www.cde.org.cn/main/xxgk/listpage/da6efd086c099b7fc949121166f0130c

[2] Novartis Phase III Data Confirms Sustained Efficacy and Long-Term Safety of Oral Remibrutinib in Chronic Spontaneous Urticaria. Retrieved Jun 1, 2024, from https://mp.weixin.qq.com/s/IShl6DL1wI86l8WK-mn03A

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