Zeposia Provides Longterm Benefit to Patients with Poorly Treated Ulcerative Colitis

Credit: Pexels / Andrea Piacquadio

Findings from a last-stage clinical trial and open-label extension show that patients with poorly controlled ulcerative colitis (UC) who are naive to advanced or biologic therapies may benefit from ozanimod (Zeposia).

Results from the phase 3 trial showed Zeposia's rapid onset of action that resulted in symptomatic response and remissions in greater proportions of patients receiving the drug versus those receiving placebo in as soon as 2 weeks. The investigators of the trial also noted that patients naive to advanced therapy experienced significant improvements with Zeposia across all clinical and mucosal efficacy endpoints at weeks 10 and 52.

An oral, highly selective sphingosine 1-phosphate receptor modulator, Zeposia has been approved to treat moderately to severely active UC in multiple countries. Initial findings from the randomized, double-blind, placebo-controlled, phase 3 True North study were used to support its US Food and Drug Administration (FDA) approval in 2021.

“Given the favorable benefit–risk ratio, ozanimod may be considered as a first-line treatment after conventional therapies,” Bruce Sands, MD, Dr Burrill B Crohn Professor of Medicine at Mount Sinai, and colleagues wrote in the recent study.

Patients in cohort one were randomly assigned in a 2:1 ratio to receive double-blind Zeposia 0.92 mg or placebo once daily in the induction period through week 10, while patients in cohort two received open-label Zeposia 0.92 mg once daily.

All patients treated with Zeposia who achieved clinical response at week 10 were re-randomized in a 1:1 ratio to receive double-blind Zeposia 0.92 mg or placebo once daily in the maintenance period through week 52. Patients who received Zeposia and achieved clinical response at week 52 could continue it in the ongoing open-label extension and were to be evaluated through week 94.

The present study results assessed Zeposia during True North and the ongoing open-label extension in patients with active disease who were exposed to conventional therapies but naive to advanced therapies. Clinical, endoscopic, and mucosal outcomes were evaluated at the end of induction and maintenance as well as at predefined open-label extension time points (week 46 and week 94).

Of the 1012 patients enrolled in True North, 616 were advanced therapy-naive. Investigators noted demographic and clinical characteristics were similar across the induction treatment groups in advanced therapy-naive patients.

At the end of induction, 62 percent of advanced therapy-naive patients on Zeposia from cohorts one and two achieved clinical response and were rerandomized to receive placebo or ozanimod. Investigators observed that 82 advanced therapy-naive patients maintained clinical response while on continuous Zeposia treatment during the induction period and maintenance period and subsequently entered the open-label extension. A total of 122 advanced therapy-naive patients who did not achieve a clinical response to Zeposia at week 10 subsequently entered the open-label extension.

By week two, numerically greater proportions of patients receiving Zeposia than placebo achieved symptomatic response, with significant differences achieved by week four. Investigators observed similar trends when looking at rates of symptomatic remission with Zeposia.

At week 10, clinical remission was achieved by a significantly greater proportion of advanced therapy-naive patients who received Zeposia in cohort one compared with placebo.

In advanced therapy-naive patients who entered the open-label extension in clinical response after 52 weeks of Zeposia treatment in True North, investigators pointed out 90.9 percent maintained clinical response after an additional two years of Zeposia at open-label extension week 94. Clinical remission, endoscopic improvement, mucosal healing, and corticosteroid-free remission were achieved by a majority of all patients.

In advanced therapy-naive patients who failed to achieve a clinical response after 10 weeks of Zeposia induction therapy, a majority were able to achieve symptomatic response with an additional five and 10 weeks of Zeposia treatment in the open-label extension, respectively, and 18.4 and 23.9 percent achieved symptomatic remission at open-label extension weeks five and 10, respectively.

Investigators noted safety outcomes in advanced therapy-naive patients were consistent with the total True North population. Although a single death occurred in a patient receiving Zeposia during the induction period, the patient had a history of ischemic cardiomyopathy, prolonged tobacco use and developed influenza and acute respiratory distress syndrome. Otherwise, incidences of bradycardia, cancer, herpes zoster, serious infections, and macular edema were low with Zeposia.

Investigators noted several potential limitations to these findings, including True North’s lack of power to investigate patient subpopulations, the lack of control of groups and blinding in the open-label extension, and the lack of generalizability of the study population to the broader advanced therapy-naive population in clinical settings.

“This analysis of advanced therapy-naive patients demonstrated that ozanimod has rapid onset of high and durable efficacy rates across clinical and mucosal outcomes and a favorable safety profile,” investigators concluded. “These data inform the early use of ozanimod in patients who require an advanced therapy and suggest that ozanimod may be optimally positioned after or in combination with mesalamine and before corticosteroids, particularly in those with moderate endoscopic disease.”

An original version of this article was published on sister site HCPLive.