Data presented at the Congress of the European Crohn’s and Colitis Organisation support further development of ST-0529 — a low-dose, controlled-release formulation of cyclosporine — for the treatment of ulcerative colitis.
Stuart Bloom, DM, FRCP, of University College London Hospitals in the United Kingdom, said cyclosporine is effective both intravenously and orally, but is usually limited to induction therapy because of its systemic side effects.
“We know that topical cyclosporine enemas result in colonic tissue concentrations comparable to those measured after intravenous administration,” he said during his presentation. “The investigators in this study therefore hypothesized that an oral preparation of cyclosporine that is targeted for delivery to the colon will be effective but have low bioavailability resulting in reduced side effects.”
Researchers recruited patients with mild to moderate UC for a double-blind, placebo-controlled phase 2a study of ST-0529. They randomly assigned patients to receive either 75 mg of the drug once daily (n = 53) or a placebo (n = 65) for 4 weeks. A previous phase 1 dose-ranging study of ST-0529 demonstrated improvement in tissue concentration when given twice daily.
The primary outcome of the study was induction of clinical remission (Disease Activity Index score no more than 2 with no individual score greater than 1 and a rectal bleeding subscore of 0 or 1). Researchers also assessed clinical response, as well as safety and tolerability of the drug.
Investigators found that ST-0529 had a slight advantage compared with placebo in clinical remission (13.2% vs. 6.3%) and clinical response (30.2% vs. 18.8%). However, the difference was not statistically significant.
In a post hoc analysis stratified for severity of disease, researchers found that differences in clinical response achieved statistical significance in some subgroups, particularly among patients taking 5-aminosalicylates or steroids.
When taken with the results of the phase 1 study, Bloom concluded that the data supported continued development of ST-0529 for the induction and maintenance of remission in patients with UC. – by Alex Young
Reference: Bloom S, et al. Abstract OP16. Presented at: Congress of the European Crohn’s and Colitis Organisation; Mar. 7-9, 2019; Copenhagen.
Disclosure: Bloom reports participating on advisory boards for Janssen, Johnson & Johnson, Pfizer, Shire, Takeda, Tillots and Vifor. Please see the ECCO disclosure database for all other authors’ relevant financial disclosures.