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The Phase 3 CROSSING trial showed tezepelumab improved histologic remission and dysphagia symptoms through week 52 in eosinophilic esophagitis.
Tezepelumab (Tezspire) met both co-primary endpoints and all key secondary endpoints in the phase 3 CROSSING trial in patients with eosinophilic esophagitis (EoE), according to AstraZeneca and Amgen, with effects sustained through week 52 across both doses tested.¹
The co-primary endpoints, assessed at week 24, were histologic remission and the frequency and severity of dysphagia relative to placebo.¹ Investigators enrolled patients who remained symptomatic and uncontrolled on maintenance therapy, a population for which current first-line options, including dietary restriction, swallowed topical corticosteroids, and proton pump inhibitors, leave nearly half of patients without adequate disease control.1
"Despite the availability of first-line therapies or dietary interventions, many patients with eosinophilic esophagitis still experience substantial burden, including difficulty swallowing food and emotional and daily-life impacts of the disease," said lead investigator Arjan Bredenoord, MD, gastroenterologist and professor, Amsterdam University Medical Center, in a statement.1 "The impressive results from the CROSSING trial sustained over 52 weeks demonstrate that tezepelumab, taken every 4 weeks, could provide a new approach to treating this disease, with the potential to help more patients achieve remission and symptom improvement."
The results mark the third epithelial-driven inflammatory disease in which tezepelumab, a first-in-class monoclonal antibody targeting thymic stromal lymphopoietin (TSLP), has demonstrated clinically meaningful efficacy, following severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP).1 Tezepelumab is approved for severe asthma in > 70 countries, including the US, and for CRSwNP in the US, EU, China, and Japan.2,3 The FDA granted tezepelumab orphan drug designation for EoE in October 2021.4
CROSSING is a randomized, double-blind, placebo-controlled, multicenter, parallel-group phase 3 trial evaluating subcutaneous tezepelumab dosed every 4 weeks against placebo in patients aged 12 to 80 years with symptomatic, histologically active EoE.¹ Investigators randomized 368 patients in a 1:1:1 ratio to a low dose of tezepelumab, a high dose, or placebo, with background EoE medications, including proton pump inhibitors and swallowed topical corticosteroids, permitted if patients remained on stable regimens through the treatment period.¹
At week 24, tezepelumab produced statistically significant and clinically meaningful improvements in histologic remission, defined as a peak esophageal eosinophil count of ≤ 6 eosinophils per high-power field, compared with placebo.¹ The trial's second co-primary endpoint, mean change from baseline in the Dysphagia Symptom Questionnaire (DSQ), a 4-item, patient-reported daily diary scored from 0 to 84 over 14-day intervals, also favored tezepelumab over placebo.¹ Both co-primary results were maintained through week 52 in the low- and high-dose arms.¹
Key secondary endpoints assessed histologic remission and dysphagia symptoms at week 52, along with changes in endoscopic disease features measured by the EoE Endoscopic Reference Score (EoE-EREFS) and histologic severity and extent measured by the EoE Histology Scoring System (EoE-HSS) at weeks 24 and 52.¹ Additional week 52 secondary endpoints included endoscopic response, inflammatory remission, and total endoscopic remission, all of which favored tezepelumab over placebo.¹
The safety profile observed in CROSSING was generally consistent with tezepelumab's established safety profile in its approved indications, according to AstraZeneca.1 No new safety signals emerged across either the low- or high-dose arms, per the release.1 AstraZeneca and Amgen plan to present full safety and secondary endpoint data from CROSSING at an upcoming medical meeting and to share findings with regulatory authorities.1
"The positive results of the Phase III CROSSING trial reinforce our confidence in the differentiated mechanism of action of Tezspire, which has now demonstrated clinically meaningful efficacy in a third epithelial-driven inflammatory disease,” said Sharon Barr, executive vice president of BioPharmaceuticals Research and Development at AstraZeneca, in the statement.1
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