Drug Overview
Cenicriviroc (Allergan/Takeda) is a potent immunomodulator that blocks the chemokine receptors-2/5 (CCR-2/5). CCR-2/5 have been linked to the inflammatory and fibrogenic pathways in non-alcoholic steatohepatitis (NASH), and by inhibiting CCR-2/5 it is anticipated that cenicriviroc will reduce inflammation and fibrosis.
Cenicriviroc has had mixed clinical trial results, which will likely lead to moderate uptake if it gains approval as a treatment for NASH. In the Phase IIb CENTAUR study, cenicriviroc failed to meet the primary endpoint based on the number of patients who experienced a two-point or greater reduction in the Non-Alcoholic Fatty Liver Disease Activity Score (NAS) with no worsening of fibrosis compared to placebo. Cenicriviroc also failed to demonstrate a statistically significant reduction in fibrosis by at least one stage with no worsening of NASH after two years of treatment versus placebo, although there was a numerical trend in cenicriviroc’s favor. As such, the inconsistent results raise concern over the strength of the signal. However, cenicriviroc did demonstrate a statistically significant increase in the number of patients who experienced a reduction in fibrosis stage after one year of therapy, with numerically higher reductions in patients with higher fibrosis stage at baseline. Moreover, when F2 and F3 patients were pooled, cenicriviroc’s benefits were significant, with the greatest effects in F3 patients. While the pivotal AURORA study is selectively enrolling patients with stage 2/3 fibrosis (CENTAUR enrolled patients with stage 1–3 fibrosis), Phase III NASH trials have more stringent endpoints, therefore it is unlikely that cenicriviroc will produce stronger fibrosis data than Ocaliva (obeticholic acid; Intercept Pharmaceuticals) in the Phase III REGENERATE trial.
Cenicriviroc (Allergan/Takeda) is a potent immunomodulator that blocks the chemokine receptors-2/5 (CCR-2/5). CCR-2/5 have been linked to the inflammatory and fibrogenic pathways in non-alcoholic steatohepatitis (NASH), and by inhibiting CCR-2/5 it is anticipated that cenicriviroc will reduce inflammation and fibrosis.
Cenicriviroc has had mixed clinical trial results, which will likely lead to moderate uptake if it gains approval as a treatment for NASH. In the Phase IIb CENTAUR study, cenicriviroc failed to meet the primary endpoint based on the number of patients who experienced a two-point or greater reduction in the Non-Alcoholic Fatty Liver Disease Activity Score (NAS) with no worsening of fibrosis compared to placebo. Cenicriviroc also failed to demonstrate a statistically significant reduction in fibrosis by at least one stage with no worsening of NASH after two years of treatment versus placebo, although there was a numerical trend in cenicriviroc’s favor. As such, the inconsistent results raise concern over the strength of the signal. However, cenicriviroc did demonstrate a statistically significant increase in the number of patients who experienced a reduction in fibrosis stage after one year of therapy, with numerically higher reductions in patients with higher fibrosis stage at baseline. Moreover, when F2 and F3 patients were pooled, cenicriviroc’s benefits were significant, with the greatest effects in F3 patients. While the pivotal AURORA study is selectively enrolling patients with stage 2/3 fibrosis (CENTAUR enrolled patients with stage 1–3 fibrosis), Phase III NASH trials have more stringent endpoints, therefore it is unlikely that cenicriviroc will produce stronger fibrosis data than Ocaliva (obeticholic acid; Intercept Pharmaceuticals) in the Phase III REGENERATE trial.
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