Evommune's EVO756 Misses Primary End Point in Phase 2b CSU Trial, Development Continues in AD and Migraine

Evommune recently reported top-line results from its phase 2b trial evaluating EVO756 in adults with moderate –to severe chronic spontaneous urticaria (CSU), with the investigational oral MRGPRX2 antagonist failing to meet its primary efficacy end point. The company said the findings do not support further development of EVO756 for CSU but will continue advancing the therapy in atopic dermatitis (AD) and migraine.¹

The randomized, double-blind, placebo-controlled, dose-ranging phase 2b study enrolled 160 patients with moderate–to severe antihistamine-refractory CSU across the United States, Europe, Canada, and Japan. Participants were randomized to receive 1 of 3 active dose regimens of EVO756 or placebo. The study did not meet its primary end point of mean change from baseline in Urticaria Activity Score over 7 days (UAS7) at week 12, with none of the active treatment groups demonstrating improvement over placebo.¹

“EVO756 previously delivered positive Phase 2 data in chronic inducible urticaria and showed clear target engagement in the Phase 1 trial, however, the lack of efficacy demonstrated at Week 12 in this Phase 2b trial does not support further development of EVO756 for CSU,” Eugene Bauer, MD, chief medical officer of Evommune, said in a statement.¹ “We are evaluating EVO756 in additional indications, and this Phase 2b trial confirmed safe and well tolerated doses that warrant these further studies.”

The company reported no new safety signals, noting that EVO756 was safe and well tolerated across all active dose groups.

Earlier Promise in MRGPRX2 Inhibition

The findings contrast with earlier clinical data for EVO756 in chronic inducible urticaria (CIndU), where the oral therapy demonstrated promising activity in a proof-of-concept study. As previously reported by Dermatology Times, approximately 30% of patients achieved a complete response after 4 weeks of treatment, while roughly 70% experienced some degree of clinical improvement, supporting continued evaluation of MRGPRX2 inhibition in mast cell-mediated diseases.²

In a previous interview with Dermatology Times, Mark Jackson, MD, senior vice president of clinical development at Evommune, said the receptor represents a potential therapeutic target because it is expressed on both mast cells and peripheral sensory neurons. He noted that inhibiting MRGPRX2 could provide a novel oral treatment strategy across multiple inflammatory diseases, including AD, by targeting both inflammation and neuroimmune signaling.³

Pipeline Focus Shifts to AD and Migraine

“While we are disappointed with the trial results in this indication, we continue to believe that modulation of MRGPRX2 represents a new potential therapeutic option to reduce inflammation and provide rapid relief of symptoms,” Luis Peña, president and chief executive officer of Evommune, said in the company's announcement.¹

According to Peña, Evommune remains on track to report top-line phase 2b data evaluating EVO756 in AD during the third quarter of 2026. The company has also initiated patient screening for a separate phase 2b study investigating EVO756 as a migraine prophylaxis, with dosing expected to begin in the near term.

Beyond EVO756, Evommune continues to advance EVO301, its long-acting injectable IL-18BP fusion protein designed to neutralize aberrantly upregulated IL-18 activity. The company recently reported positive phase 2a proof-of-concept data for EVO301 in AD and plans to initiate a phase 2b clinical trial.

Peña also noted that Evommune expects its current cash position to support operations through 2028, positioning the company to continue advancing its inflammatory disease pipeline despite the CSU setback.

Although EVO756 will no longer be developed for CSU, Evommune's near-term focus now shifts to the ongoing phase 2b AD program, with top-line results expected in the third quarter of 2026, as well as the newly initiated migraine prophylaxis study.

References

1. Evommune announces top-line results from EVO756 phase 2b trial in moderate-to-severe chronic spontaneous urticaria. News release. Evommune, Inc. June 29, 2026. Accessed June 29, 2026. https://ir.evommune.com/news-events/press-releases/detail/124/evommune-announces-top-line-results-from-evo756-phase-2b-trial-in-moderate-to-severe-chronic-spontaneous-urticaria
2. Hebebrand M. Targeting MRGPRX2: early human data for a novel CSU approach. Dermatology Times. February 10, 2026. Accessed June 29, 2026. https://www.dermatologytimes.com/view/targeting-mrgprx2-early-human-data-for-a-novel-csu-approach
3. Andrus E. Exploring EVO756 in chronic inflammatory diseases treatment: Q&A with Evommune’s Mark Jackson, MD. Dermatology Times. December 17, 2024. Accessed June 29, 2026. https://www.dermatologytimes.com/view/exploring-evo756-in-chronic-inflammatory-disease-treatment-q-a-with-evommune-s-mark-jackson-md