Saroglitazar in PBC: biochemical response in 57% against 10% on placebo

Design

Phase 2b/3 adaptive, double-blind, placebo-controlled trial (EPICS-III)

Population

148 adults with PBC and inadequate response or intolerance to UDCA

Primary outcome

Composite biochemical response at 52 weeks

Effect

56.7% vs 9.8%; difference 48.0 points (95% CI 35.3 to 60.8)

EPICS-III was a phase 2b/3 adaptive, double-blind randomised trial in primary biliary cholangitis with inadequate response to or intolerance of ursodeoxycholic acid. After dose-finding, 148 patients were randomised to saroglitazar 1 mg or placebo for 52 weeks.

The primary composite biochemical response — alkaline phosphatase under 1.67 times the upper limit with at least a 15% fall, and normal bilirubin — was reached by 56.7% on saroglitazar and 9.8% on placebo (difference 48.0 points, 95% CI 35.3 to 60.8). Among those starting with alkaline phosphatase three times normal or less, response was 79.0% against 14.3%. Alkaline phosphatase normalised in 8.2% against none. Itch improved at 24 weeks in those with significant itch, but not at 52 weeks. Serious adverse events were 6.3% against 11.1%.

Second-line options for PBC have expanded with PPAR agonists, and this adds one more. Saroglitazar is developed and already marketed in India for other indications, which may affect access and cost; whether it is licensed for PBC here should be checked. The endpoint is biochemical, and effects on transplant-free survival are not yet known.

• Check biochemical response to ursodeoxycholic acid at 6–12 months in every patient with PBC.
• Consider a PPAR agonist, including saroglitazar where licensed, for inadequate response.
• Monitor liver tests, weight and renal function on PPAR agonists.
• Do not expect lasting itch relief from saroglitazar on this evidence.

Why it matters

A drug already familiar to Indian prescribers now has phase 3 evidence in a disease with few second-line choices.

Don't overread it

A biochemical surrogate over one year; clinical outcomes are not yet shown.

The statistics, in plain English

A 48-point absolute difference is large: about two extra responders for every four patients treated. Biochemical response is a surrogate linked to better long-term outcomes, but the trial did not measure liver failure, transplant or death. The saroglitazar group started with somewhat higher liver tests.

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