Lepodisiran, a Small Interfering Therapy Significantly Lowers Lipoprotein(a) Level
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Reviewed by Dat Tien Nguyen, B.A, ScM.
Translated by Nhi Phuong Quynh Le, B.A |
Posted on May 26th, 2025
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Chronic inflammation of the colonic epithelium underlies ulcerative colitis, a condition that can significantly impair quality of life and elevate the long-term risk of colorectal cancer. While various treatments are available, many fall short in preventing disease relapse or carry undesirable side effects. To explore new therapeutic options, a study funded by Ventyx Biosciences evaluated the potential of tamuzimod for managing ulcerative colitis.
This phase 2 clinical trial enrolled 213 patients with moderate-to-severe ulcerative colitis, confirmed by either endoscopy or histological analysis. At baseline, the average modified Mayo score—a measure of disease activity—was approximately 6.5 out of 9. Most participants (80%) were on oral 5-aminosalicylic acid, and around 25% were receiving corticosteroids. Participants were randomly assigned to receive either a placebo or tamuzimod at a daily dose of 30 mg or 60 mg. Tamuzimod is a selective inhibitor of the sphingosine-1-phosphate receptor 1 (S1PR1), a target essential for lymphocyte trafficking to secondary lymphoid organs. By inhibiting this receptor, tamuzimod limits the migration of lymphocytes to inflamed colonic tissue.
After 12 weeks of treatment, both doses of tamuzimod led to higher rates of clinical remission compared to placebo. These improvements were supported by endoscopic and histologic evidence as well as symptomatic relief. The drug also induced a roughly 65% reduction in circulating lymphocytes. Importantly, tamuzimod was well-tolerated—unlike other S1PR inhibitors, it was not associated with bradycardia, and no increased risk of infection was observed despite the reduced lymphocyte count.
This phase 2 clinical trial enrolled 213 patients with moderate-to-severe ulcerative colitis, confirmed by either endoscopy or histological analysis. At baseline, the average modified Mayo score—a measure of disease activity—was approximately 6.5 out of 9. Most participants (80%) were on oral 5-aminosalicylic acid, and around 25% were receiving corticosteroids. Participants were randomly assigned to receive either a placebo or tamuzimod at a daily dose of 30 mg or 60 mg. Tamuzimod is a selective inhibitor of the sphingosine-1-phosphate receptor 1 (S1PR1), a target essential for lymphocyte trafficking to secondary lymphoid organs. By inhibiting this receptor, tamuzimod limits the migration of lymphocytes to inflamed colonic tissue.
After 12 weeks of treatment, both doses of tamuzimod led to higher rates of clinical remission compared to placebo. These improvements were supported by endoscopic and histologic evidence as well as symptomatic relief. The drug also induced a roughly 65% reduction in circulating lymphocytes. Importantly, tamuzimod was well-tolerated—unlike other S1PR inhibitors, it was not associated with bradycardia, and no increased risk of infection was observed despite the reduced lymphocyte count.