A major clinical trial offers promising news for people living with eosinophilic esophagitis (EoE), a chronic inflammatory condition that can make swallowing difficult and painful. Amgen and AstraZeneca have announced full results from their Phase 3 CROSSING trial evaluating Tezspire (tezepelumab-ekko), an injectable medication already approved for certain other inflammatory conditions. The study found that Tezspire significantly reduced inflammation in the esophagus—the tube connecting the mouth to the stomach—and improved swallowing difficulties in adolescents and adults with uncontrolled EoE. The benefits continued through a full year of treatment.
EoE occurs when white blood cells called eosinophils build up in the esophagus, causing inflammation that can lead to scarring and narrowing. Food may move slowly or become stuck, making everyday meals stressful and sometimes dangerous. Existing treatments include elimination diets, acid-reducing medications, and swallowed steroids, but many patients continue to struggle with symptoms. As trial investigator Dr Evan Dellon of the University of North Carolina School of Medicine explained, “The prevalence of eosinophilic esophagitis is on the rise and has become one of the fastest-growing chronic gastrointestinal conditions we see in the clinic.” He noted that many patients live with the near-daily fear of food becoming stuck while eating.
The CROSSING trial enrolled 368 patients ages 12 to 80, who were randomly assigned to receive Tezspire at either a 210 mg or 420 mg dose, or a placebo, by injection every four weeks. After 24 weeks, 64.8% of patients receiving the lower dose and 68.9% receiving the higher dose achieved histologic remission, compared with just 3.5% of those receiving placebo. Histologic remission means that tissue samples examined under a microscope showed a substantial reduction in the inflammatory cells associated with EoE. Patients receiving Tezspire also reported significant improvements in the frequency and severity of swallowing difficulties.
Those improvements continued through the full 52-week study. At the one-year mark, 67.8% of patients receiving the 210 mg dose and 63.3% receiving the 420 mg dose remained in histologic remission, compared with 5.4% of the placebo group. Swallowing symptoms also continued to improve. Dr Jay Bradner, executive vice president of Research and Development, Artificial Intelligence and Data at Amgen, emphasized the need for additional treatment options, noting that approximately half of people with EoE continue to experience uncontrolled symptoms despite standard treatments. He described the trial’s sustained improvements as statistically significant and clinically meaningful.
The benefits extended beyond microscopic tissue samples and patient-reported symptoms. Doctors also used endoscopy—a procedure involving a small camera inserted into the esophagus—to look for visible signs of disease. After 52 weeks, 34.4% of patients receiving the lower Tezspire dose and 29.5% receiving the higher dose achieved total endoscopic remission, compared with just 4.1% receiving placebo. This meant doctors found no visible signs of EoE using the study’s standardized scoring system, which evaluates swelling, rings, white patches, grooves, and narrowing in the esophagus. Importantly, patients were allowed to continue certain existing EoE treatments, including acid-reducing medications and swallowed steroids, as long as their regimens remained stable. Dr Arjan Bredenoord of Amsterdam University Medical Center, another trial investigator, highlighted the importance of the sustained improvements, particularly among patients who remained on their existing therapies.
Tezspire’s safety profile in the trial was generally consistent with its approved uses. The most commonly reported side effects included inflammation of the nose and throat, headaches, and diarrhea. The medication also carries warnings about serious allergic reactions, including anaphylaxis, which has been reported following its use. One serious anaphylactic reaction was considered possibly related to Tezspire in the CROSSING trial. Tezspire is already FDA-approved for severe asthma and chronic rhinosinusitis with nasal polyps, but it has not yet been approved to treat EoE. Additional regulatory review would be required before it could be marketed specifically for this condition.
Tezspire works by blocking a protein called thymic stromal lymphopoietin (TSLP), which helps trigger the chain of immune reactions responsible for inflammation. By interrupting this process, the medication may offer a new approach for controlling EoE in patients who do not respond adequately to existing therapies. Although the findings do not establish a cure or guarantee that patients can return to normal eating, the combination of reduced inflammation, improved swallowing, and fewer visible signs of disease represents an encouraging advance. If approved for EoE, Tezspire could become another important option for people managing this challenging chronic condition.
