Novartis Reports Positive Phase III Outcomes for Novel Chronic Spontaneous Urticaria Drug

Novartis Reports Positive Phase III Outcomes for Novel Chronic Spontaneous Urticaria Drug

TOP-LINE DATA FROM REMIX-1 AND REMIX-2 STUDIES DEMONSTRATE SIGNIFICANT SYMPTOM IMPROVEMENT

(IN BRIEF) Novartis has unveiled promising results from Phase III trials for remibrutinib, a potent Bruton’s tyrosine kinase (BTK) inhibitor, targeting chronic spontaneous urticaria (CSU). The REMIX-1 and REMIX-2 studies, involving 470 and 455 participants respectively, achieved their primary and secondary endpoints, showing substantial reduction in disease activity. Patients on remibrutinib witnessed rapid improvements as early as Week 2, and the treatment’s safety profile remained favorable. These breakthrough findings suggest that remibrutinib could potentially become a pioneering oral treatment for refractory CSU symptoms. Chronic spontaneous urticaria impacts millions globally, and current treatments are ineffective for many. Remibrutinib’s unique mechanism of inhibiting histamine release holds promise for managing these distressing symptoms. Novartis intends to present comprehensive data at upcoming medical meetings and commence submissions to health authorities in 2024.

(PRESS RELEASE) BASEL, 9-Aug-2023 — /EuropaWire/ — Novartis has revealed encouraging outcomes from its Phase III REMIX-1 and REMIX-2 trials investigating the effectiveness of remibrutinib 25 mg b.i.d., a potent Bruton’s tyrosine kinase (BTK) inhibitor, for patients grappling with inadequately controlled chronic spontaneous urticaria (CSU)1. These groundbreaking studies, encompassing 470 and 455 participants respectively, successfully met all primary and secondary endpoints, signaling a significant breakthrough in the management of this condition1.

The primary goal of these trials was to ascertain the absolute change from baseline in the weekly urticaria activity score (UAS7) at Week 12, a target that was admirably achieved, highlighting notable reductions in disease activity1. The rapid onset of remibrutinib’s effectiveness was also observed, with substantial improvements evident as early as Week 21. Notably, remibrutinib’s safety profile remained favorable, including liver function tests, as evidenced in both active and placebo arms across both studies1.

“CSU has a profound impact on patients’ lives, necessitating effective, convenient, and well-tolerated treatments that can swiftly mitigate its debilitating symptoms,” noted Shreeram Aradhye, M.D., President, Global Drug Development and Chief Medical Officer at Novartis. “The promising results from REMIX studies suggest that remibrutinib, a highly selective BTK inhibitor, could emerge as a pioneering, oral treatment for individuals with refractory CSU symptoms.”

Chronic spontaneous urticaria, a condition characterized by persistent hives (wheals) and deep tissue swelling (angioedema), affects approximately 40 million people worldwide and leads to a significant reduction in patients’ quality of life3–6. While H1-antihistamines serve as the primary treatment for CSU, nearly 60% of patients continue to grapple with uncontrolled symptoms2. Remibrutinib’s mechanism of inhibiting BTK, a central enzyme responsible for histamine release, provides a promising avenue for addressing the distressing symptoms associated with CSU9.

Remibrutinib, developed by Novartis, stands out as a selective oral BTK inhibitor, offering the potential to rapidly and sustainably manage CSU symptoms within a two-week timeframe of initiation. Beyond CSU, remibrutinib’s potential extends to other immune-mediated conditions, such as multiple sclerosis, hidradenitis suppurativa, food allergy, and Sjögren’s syndrome10–13. Current participants in REMIX-1 and REMIX-2 will be provided with the opportunity to continue treatment up to Week 52 and engage in a long-term extension trial14,15.

Novartis anticipates presenting the comprehensive REMIX data at forthcoming medical meetings and intends to commence submissions to global health authorities beginning in 2024.

About remibrutinib
Remibrutinib is a highly selective, oral Bruton’s tyrosine kinase (BTK) inhibitor that blocks the BTK cascade and prevents the release of histamine that causes itch, hives/welts and swelling9,16. In Phase II studies, remibrutinib demonstrated fast onset of action and sustained efficacy in patients with moderate to severe chronic spontaneous urticaria (CSU)9. Remibrutinib has been shown to be well-tolerated across all doses studied in Phase II9. These results have now been confirmed by the Phase III REMIX data1. In addition to CSU, remibrutinib is being investigated in other immune-mediated conditions, such as multiple sclerosis, hidradenitis suppurativa, food allergy and Sjögren’s syndrome10–13,17. If approved, remibrutinib has the potential to become an effective oral option to complement Xolair® (omalizumab), the first and only injectable biologic indicated for CSU18. In the US, Novartis Pharmaceuticals Corporation and Genentech, a member of the Roche Group, work together to develop and co-promote Xolair.

About REMIX-1 and REMIX-2
REMIX-1 (NCT05030311) and REMIX-2 (NCT05032157) are two identically designed global, multicenter, randomized, double-blind, parallel-group, placebo-controlled Phase III studies, with REMIX-1 consisting of 470 participants and REMIX-2 consisting of 455 participants (14,15). Both studies are designed to establish the efficacy, safety and tolerability of remibrutinib in adult participants with chronic spontaneous urticaria that is inadequately controlled by second generation H1-antihistamines compared with placebo (14,15). The primary outcome measures include absolute change from baseline in the weekly urticaria activity score, absolute change in itch severity score and hive severity score at Week 12 (14,15). Patients currently enrolled in REMIX-1 and REMIX-2 will continue to receive treatment up to Week 52 and will have the opportunity to continue in a long-term extension trial (14,15).

About chronic spontaneous urticaria (CSU)
CSU affects approximately 40 million people worldwide (4,5). CSU is characterized by the sudden appearance of itchy hives (wheals) and/or deep tissue swelling (angioedema) for more than 6 weeks, affecting all ages but most frequently between 20–40 years, with women affected nearly twice as often as men (3,4). CSU causes significant emotional distress, with the majority of patients suffering from sleep deprivation, and high rates of mental disorders, such as anxiety or depression (4). There are currently limited effective treatment options for CSU, with many patients not achieving full control from the first-line treatment, antihistamines (2,3,7).

About Novartis
Novartis is reimagining medicine to improve and extend people’s lives. We deliver high-value medicines that alleviate society’s greatest disease burdens through technology leadership in R&D and novel access approaches. In our quest to find new medicines, we consistently rank among the world’s top companies investing in research and development. About 103,000 people of more than 140 nationalities work together to bring Novartis products to nearly 800 million people around the world. Find out more at https://www.novartis.com

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References
1.  Novartis Data on File.
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10.  ClinicalTrials.gov. Study of Efficacy and Safety of Investigational Treatments in Patients With Moderate to Severe Hidradenitis Suppurativa. NCT03827798. Available at: https://clinicaltrials.gov/ct2/show/NCT03827798?term=LOU064&cond=Hidradenitis+Suppurativa&draw=2&rank=1 [Last accessed: August 2023].
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13.  ClinicalTrials.gov. Study of Efficacy, Safety and Tolerability of Remibrutinib in Adult Participants With an Allergy to Peanuts. NCT05432388. Available at: https://clinicaltrials.gov/study/NCT05432388?cond=Food%20Allergy&term=LOU064&rank=2 [Last accessed: August 2023].
14.  ClinicalTrials.gov. A Phase 3 Study of Efficacy and Safety of Remibrutinib in the Treatment of CSU in Adults Inadequately Controlled by H1 Antihistamines (REMIX-1). NCT05030311. Available at: https://clinicaltrials.gov/ct2/show/NCT05030311 [Last accessed: August 2023].
15.  ClinicalTrials.gov. A Phase 3 Study of Efficacy and Safety of Remibrutinib in the Treatment of CSU in Adults Inadequately Controlled by H1 Antihistamines (REMIX-2). NCT05032157. Available at: https://clinicaltrials.gov/ct2/show/NCT05032157 [Last accessed: August 2023].
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17.  ClinicalTrials.gov. A Phase 2 Study to Evaluate the Safety and Efficacy of LOU064 in Patients With Moderate to Severe Sjögren’s Syndrome (LOUiSSe). NCT04035668. Available at: https://clinicaltrials.gov/study/NCT04035668?cond=Sjogren%27s%20Syndrome&term=remibrutinib&rank=1 [Last accessed: August 2023].
18.  Xolair Omalizumab. Chronic Spontaneous Urticaria (CSU). Available at: https://www.xolair.com/chronic-spontaneous-urticaria.html [Last accessed: August 2023].

SOURCE: Novartis