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About Chronic Spontaneous Urticaria

Chronic spontaneous urticaria (CSU) is a severely debilitating, chronic inflammatory skin disease with no identified triggers¹. Clinical manifestations include hives, angioedema, or both.¹ Hives are variable in size and shape and are characterized by swelling, itchiness, and/or a burning sensation¹. Angioedema is characterized by pronounced deep tissue swelling along with tingling, burning, tightness and sometimes pain¹. Patients with CSU also experience symptoms beyond the skin manifestations, including sleep disturbances, fatigue, irritability, anxiety, and depression.² CSU is typically a self-limiting disorder, persisting for 2–5 years² although some reports estimate that more than half of patients suffer for more than 5 years³.  CSU may also recur after months or years of full remission.¹  CSU can be severely disabling, significantly impair quality of life, and affect performance at work or school.¹ CSU impacts twice as many women as men, with an estimated global prevalence between 0.5% – 1% of the population.⁴ This means that at any given time in the U.S. alone approximately 1.75-3.5 million people are experiencing this condition.⁴ The peak age of diagnosis is during the core years of working age (20 – 40 years old).⁴ Standard of care treatment for CSU is antihistamines, however in approximately half the patients, symptom alleviation is not adequate. There is a substantial unmet need for an efficacious oral agent as only a minority of these uncontrolled cases are treated with one indicated biologic (<28%).⁵

Enanta’s Approach to Treating CSU

Our approach to treating CSU is to directly target mast cells which are the root cause of pathology. Mast cells are tissue-resident immune cells that have been implicated as the driver of multiple inflammatory diseases, including chronic urticaria, prurigo nodularis, asthma, and atopic dermatitis. We are targeting mast cells by inhibiting KIT, a central regulator of mast cell development and activation. As a tyrosine kinase receptor, KIT provides pro-survival signals to mast cells and, therefore, KIT inhibition blocks these pro-survival signals, thereby leading to rapid mast cell inactivation and depletion. Current therapies modulate only a small subset of either mast cell stimulants or the downstream mediators of inflammation that mast cells produce. However, these therapies do not address the underlying cause of disease, as they do not directly affect mast cells themselves.¹

Our prototype KIT inhibitors potently inhibit activity in both binding and cellular function assays and are highly selective for KIT versus other kinases. These inhibitors also demonstrate strong in vitro and in vivo ADME properties. We are targeting 2024 for the selection of a development candidate.

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1. Zuberbier T et al. The International EAACI/GA²LEN/EuroGuiDerm/APAAACI Guideline for the Definition, Classification, Diagnosis, and Management of Urticaria. Allergy 2022.
2. Yosipovitch et al. Current and Emerging Therapies for Chronic Spontaneous Urticaria: A Narrative Review. Dermatol Ther 2023.
3. Balp M-M et al.  Clinical Remission of Chronic Spontaneous Urticaria (CSU): A Targeted Literature Review.  Dermaltol Ther 2022.
4. Maurer M et al. Unmet Clinical Needs in Chronic Spontaneous Urticaria. A GA²LEN Task Force Report. Allergy 2011.
5. Clarivate Treatment Algorithms: Claims Data Analysis – Chronic spontaneous urticaria, February 2023. ©2023 DR/Decision Resources, LLC. All rights reserved. Reproduction, distribution, transmission or publication is prohibited. Reprinted with permission.

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