Evommune Ends Development of Lead Asset in Chronic Hives After Mid-Stage Efficacy Woes

Evommune Halts Lead Asset Development After Phase 2b Failure

Evommune has halted development of its lead asset, EVO756, for chronic spontaneous urticaria following a Phase 2b study that showed no significant benefit. The oral MRGPRX2 blocker, tested in 160 antihistamine-refractory patients over 12 weeks, failed to meet its primary goal across all three tested doses. This outcome led to a more than 40% crash in Evommune's shares. The company will now focus on EVO756 in atopic dermatitis and migraine, while its anti-IL-18 therapy, EVO301, becomes the central asset, having shown promising results in a Phase 2a eczema trial.

• Evommune's oral MRGPRX2 blocker, EVO756, failed to demonstrate significant efficacy in a Phase 2b study for moderate-to-severe chronic spontaneous urticaria. The trial, involving 160 antihistamine-refractory patients, did not meet its primary endpoint of reducing disease activity at 12 weeks across any of the three tested doses, leading to the cessation of its development for this indication.
• Following the disappointing Phase 2b results, Evommune's shares plummeted over 40%. The company will discontinue EVO756's development in chronic spontaneous urticaria but plans to continue its study in atopic dermatitis and migraine. This strategic shift positions the therapeutic protein EVO301 as the company's primary value driver, according to analyst firms like Oppenheimer and William Blair.
• Evommune's anti-IL-18 therapy, EVO301, is now the focus of the company's pipeline. Earlier Phase 2a data in atopic dermatitis showed a 33% placebo-adjusted reduction in eczema severity at 12 weeks. EVO301 is also in Phase 1 development for ulcerative colitis, with analysts projecting a Phase 2b trial start in mid-2027 and results in late 2028, highlighting its potential as a blockbuster asset.

Understanding the Failed EVO756 Chronic Urticaria Trial

Clinical trials in chronic spontaneous urticaria (CSU) span a range of designs — from randomized controlled trials to retrospective cohort studies and prospective observational studies — reflecting both the therapeutic breadth and evolving endpoint standardization in this field. The UAS7 (7-day Urticaria Activity Score) has emerged as the dominant primary efficacy endpoint across trials, supplemented by patient-reported outcomes and quality-of-life measures.

The Persistent Unmet Need in Chronic Spontaneous Urticaria

Despite advances in the treatment landscape, chronic spontaneous urticaria (CSU) remains a condition without a cure — with available pharmacological therapies offering only symptomatic control and failing to regulate the inflammatory balance of the skin in the long term. Guideline-recommended treatment escalation improves disease control in some patients, yet a substantial proportion remain inadequately managed, underscoring a persistent and multidimensional unmet need.

• Inadequate response to standard-of-care therapies: Many patients remain symptomatic despite second-generation H1-antihistamines (sgH-AH), and a significant subset is refractory to both H1-antihistamines and omalizumab — the two pillars of current guideline-directed therapy.

• Low complete response rates across treatment escalation steps: Complete response rates following escalation are strikingly low: only 5.3% of patients escalating from no treatment to licensed-dose sgH-AH, 6.0% escalating from licensed-dose to up-dosed sgH-AH, and 28.4% escalating from any sgH-AH dose to omalizumab achieved complete response — with only approximately one quarter of patients achieving complete response through appropriate escalation overall.

• Widespread failure to escalate therapy in eligible patients: Approximately 28.6% of patients clinically eligible for treatment escalation (UCT < 12) at baseline did not receive step-up therapy (18.0%) or were even stepped down (10.6%), remaining poorly controlled at follow-up — reflecting a significant gap between guideline recommendations and real-world practice.

• Substantial patient-reported unmet needs: Among Italian patients, the primary unmet need was treatments with fewer side effects (39.1%), alongside demand for more effective therapies. Patients also reported freedom from itch and hives as their top treatment expectation (7.69/10).

• Considerable HRQoL burden: CSU imparts a substantial disease burden, with Italian patients rating its negative impact at 6.3/10; reduced confidence was cited as the top impact domain (28.1%), highlighting the psychosocial dimensions of the disease that current therapies fail to adequately address.

• Need for novel therapeutic modalities: For patients refractory to conventional therapy, including H1-antihistamines and omalizumab, additional safe and effective treatment options are required — with agents such as cyclosporine and immunosuppressants, as well as adjunctive approaches such as probiotics, under investigation but not yet established as standard options.