A phase 2b trial of Evommune’s EVO756 has missed its primary endpoint, wiping out a would-be rival to Novartis for the chronic spontaneous urticaria (CSU) market.
The trial compared EVO756, an oral MRGPRX2 antagonist, to placebo in adults with moderate-to-severe forms of the skin condition CSU. Investigators enrolled 160 people failed by antihistamines to receive one of three doses of EVO756 or placebo. None of the doses had a statistically bigger effect than placebo on Urticaria Activity Score over seven days (UAS7) at Week 12, causing the trial to miss its primary endpoint.
Novartis is a potential beneficiary of the setback. In September 2025, the Swiss drugmaker won FDA approval for the BTK inhibitor Rhapsido in CSU, a condition characterized by hives. Novartis reported a strong start to the U.S. launch in April and is now free from one potential challenger to the CSU market.
While Evommune’s trial failed to support further development of EVO756 for CSU, the biotech continues to test the asset in a phase 2b atopic dermatitis study that is scheduled to deliver data in the third quarter. The biotech plans to start dosing patients in a phase 2b migraine prevention trial imminently.
The failed CSU trial found the three doses were safe and well tolerated, offering some encouragement for the ongoing areas of EVO756 research. But William Blair analysts warned in a June 12 note that a failure in CSU would “further reduce confidence in atopic dermatitis or other itch-related indications.” The analysts expect hopes for the atopic dermatitis trial will be very low, they said in a June 29 note.
Gil Yosipovitch, M.D., a dermatology professor at the Miller School of Medicine, told the analysts that the heterogeneous inflammatory pathways involved in atopic dermatitis could complicate efforts to treat the skin condition via MRGPRX2 antagonism.
William Blair analysts saw a strong probability of success in CSU, despite the challenges Incyte faced in the indication. Incyte acquired an MRGPRX2 inhibitor, EP262, in 2024 through its $750 million takeover of Escient Pharmaceuticals. Preclinical toxicology data drove Incyte to pause an EP262 trial in CSU. Later, clinical data showed limited placebo-adjusted difference on UAS7 change from baseline to Week 6.
The analysts saw less read-through from CSU to migraine. However, they also cautioned that Evommune likely must deliver clinical data in migraine before investors ascribe value to the indication. The analysts predicted Evommune’s share price could fall to $15 if EVO756 failed in CSU, largely reflecting the value of phase 1 IL-18 program EVO301. In reality, Evommune’s stock fell 35% to $16.45 in premarket trading Monday from a Friday closing price of $25.20.