Amgen, AZ’s Tezspire Succeeds in Phase 3 Eosinophilic Esophagitis Trial, Challenging Dupixent

Tezspire, an inflammatory disease treatment from Amgen and AstraZeneca, met all primary endpoints in a Phase 3 trial for eosinophilic esophagitis (EoE), positioning it to challenge Sanofi and Regeneron’s Dupixent.

Amgen and AstraZeneca said on the 27th (local time) that Tezspire met all primary and key secondary endpoints in the Phase 3 ‘CROSSING’ trial in EoE.

Tezspire is an anti-TSLP biologic that targets an upstream mediator of inflammation. According to the companies, at Week 24, the treatment showed statistically significant improvements in both histologic remission, defined as low eosinophil counts in the esophagus compared with placebo, and dysphagia symptoms.

The companies added that the treatment effect for both doses used in the trial on the co-primary endpoints was sustained through Week 52.

With this success, Tezspire has secured the potential to expand into a third inflammatory disease indication, following severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). The companies plan to share the study results with regulatory authorities and at future scientific conferences.

If approved, Tezspire would compete with Dupixent, which first received an EoE indication in 2022. Unlike Dupixent, which blocks the IL-4 and IL-13 signaling pathways downstream in the immune cascade, Tezspire targets upstream TSLP.

EoE is a disease in which chronic inflammation develops in the esophagus, causing it to narrow and leading to difficulty swallowing (dysphagia). According to the companies, more than 470,000 people in the United States have the disease, and its prevalence has increased in recent years.

Before the introduction of biologics, first-line EoE treatment centered on three approaches known as the “3Ds”: drugs, diet and dilation. In the CROSSING trial, patients were allowed to continue existing medications, such as proton pump inhibitors or topical steroids.

Trial lead investigator Arjan Bredenoord, a gastroenterologist at Amsterdam University Medical Center in the Netherlands, said, “Despite first-line treatment or dietary interventions, many patients with EoE continue to experience difficulty swallowing food and emotional and daily-life burdens.”

He added, “The impressive results of the 52-week CROSSING trial show that Tezspire, administered every 4 weeks, could represent a new treatment approach for this disease.”

Tezspire’s success follows AstraZeneca’s renewed effort after mixed results in the Phase 3 MESSINA trial of Fasenra, an anti-IL-5 antibody, in EoE. In 2022, Fasenra achieved histologic remission compared with placebo but failed to meet its target on the dysphagia symptom measure.

In addition to EoE, Tezspire is being studied in the Phase 3 JOURNEY and EMBARK trials for chronic obstructive pulmonary disease (COPD).

Tezspire, which received U.S. Food and Drug Administration (FDA) approval for severe asthma at the end of 2021, generated $1.9 billion in combined sales for Amgen and AstraZeneca last year. That was an increase from approximately $1.3 billion the previous year.

Dupixent, by contrast, which has broader indications beyond airway inflammation, generated global sales of $17.8 billion last year.