Phase 3 Crossing results in eosinophilic esophagitis
Amgen and AstraZeneca announced on Aug. 27 that their co-developed anti-TSLP biologic Tezspire hit all primary and key secondary endpoints in the Phase 3 Crossing trial in eosinophilic esophagitis (EoE), delivering a third potential inflammatory-disease indication for the drug. By targeting TSLP, an upstream driver of inflammation, Tezspire demonstrated statistically significant improvements versus placebo on both co-primary measures at week 24: histologic remission, defined by a low count of peak eosinophils in the esophagus, and patient-reported difficulty swallowing. The companies said the benefits on those co-primary endpoints were sustained through week 52 for both Tezspire doses tested.
How the data read out
In addition to the week-24 co-primary endpoints and week-52 key secondary endpoints, Crossing also met other measures, including endoscopic disease features and histologic severity and extent at weeks 24 and 52, as well as endoscopic response, inflammatory remission, and total endoscopic remission at week 52. Patients were permitted to remain on background first-line EoE therapies during the trial, including proton pump inhibitors and swallowed topical corticosteroids. Arjan Bredenoord, M.D., a gastroenterologist at Amsterdam University Medical Center and the trial's primary investigator, said in an Aug. 27 statement that despite the availability of first-line therapies or dietary interventions, many patients with EoE still experience substantial burden, including difficulty swallowing food and emotional and daily-life impacts, and that the sustained 52-week results show it "could provide a new approach to treating this disease."
Competitive positioning against Dupixent
A successful EoE filing would put Tezspire in direct competition with Sanofi and Regeneron's Dupixent, which became the first medicine specifically indicated for EoE in 2022. The two drugs work at different points in the immune cascade: Tezspire targets TSLP upstream, while Dupixent acts downstream by blocking IL-4 and IL-13 signaling. Amgen and AstraZeneca said they plan to share the Crossing results with regulatory authorities and present them at an upcoming medical meeting.
Expanding the Tezspire label
EoE would be Tezspire's third indication after severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). The partners are also running Phase 3 Journey and Embark trials in chronic obstructive pulmonary disease. Tezspire previously picked up another EoE contender for AstraZeneca when its anti-IL5 antibody Fasenra failed in the Phase 3 Messina trial in 2022, achieving histological remission but missing the dysphagia symptoms endpoint.
Disease context and regulatory path
Eosinophilic esophagitis is a chronic inflammatory disease of the esophagus that can lead to esophageal narrowing and difficulty swallowing, or dysphagia. Amgen and AstraZeneca estimate the disorder affects more than 470,000 people in the U.S., with prevalence rising in recent years. Before biologics, first-line treatment of EoE has centered on the so-called "3 Ds": drugs such as proton pump inhibitors and swallowed topical corticosteroids, dietary interventions, and esophageal dilation. The companies have not yet disclosed a timeline for regulatory submissions.
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