Saroglitazar in UDCA-refractory PBC: biochemical response 57% against 10%

Design

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

Population

148 patients with PBC and inadequate response or intolerance to UDCA (phase 3)

Primary outcome

Biochemical response at week 52

Effect

56.7% vs 9.8%; difference 48.0% (95% CI 35.3–60.8); ALP normalisation 8.2% vs 0%

EPICS-III was a phase 2b/3 adaptive, double-blind trial of saroglitazar, a dual PPAR-alpha/gamma agonist, in primary biliary cholangitis with an inadequate response to or intolerance of ursodeoxycholic acid. After dose selection, 148 patients were randomised to saroglitazar 0.97 mg daily or placebo for 52 weeks.

Biochemical response — ALP below 1.67 times the upper limit with at least a 15% fall, and normal bilirubin — occurred in 56.7% against 9.8% (difference 48.0%, 95% CI 35.3 to 60.8). In those with baseline ALP up to three times normal, response was 79.0% against 14.3%. ALP normalised in 8.2% against none. An itch benefit at 24 weeks in those with significant pruritus was not maintained at 52 weeks. Serious adverse events were 6.3% against 11.1%.

Biochemical response is a validated surrogate in PBC, but this trial does not report liver outcomes. Saroglitazar is already licensed in India for other indications; its regulatory status for PBC should be checked, and it joins other PPAR agonists as a second-line option.

• Check ALP and bilirubin at 6–12 months on ursodeoxycholic acid to identify inadequate response.
• Consider second-line therapy for PBC patients who do not reach biochemical response on UDCA.
• Saroglitazar response was greatest when baseline ALP was below three times normal.
• Do not expect lasting itch relief from saroglitazar on this evidence.
• Check regulatory approval for PBC before prescribing; its existing Indian licence covers other indications.

Why it matters

It adds an option, developed in India, for PBC patients who do not respond fully to UDCA.

Don't overread it

Biochemical response is a surrogate; this trial did not show fewer liver events or deaths.

The statistics, in plain English

A 48-point difference in response means about one extra responder for every two patients treated. ALP normalisation, a stricter target, was rare in both groups.

Read the rest in the app

You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.

Get Daily Doctor — free

Scan to keep reading on your phone. No account needed to start.