Saroglitazar improves biochemical response in phase 3 PBC trial

In the phase 2b/3 EPICS-III randomized trial, 148 patients with primary biliary cholangitis (PBC) and an inadequate response or intolerance to ursodeoxycholic acid received saroglitazar or placebo for 52 weeks. Biochemical response was higher with saroglitazar, while itch-score improvement at 24 weeks was not maintained at week 52.

Biochemical response: 56.7% with saroglitazar versus 9.8% with placebo.
ALP normalization occurred in 8.2% versus 0%.
Itch-score benefit at week 24 was not sustained at week 52.
Trial followed patients for 52 weeks; clinical outcomes were not reported.

EPICS-III was an adaptive, double-blind randomized trial in patients with PBC who had an inadequate response to or were intolerant of ursodeoxycholic acid. After a 16-week phase 2b dose-selection stage involving 37 participants, the phase 3 stage randomized 148 patients to saroglitazar 0.97 mg (n=97) or placebo (n=51) for 52 weeks. The primary endpoint was a biochemical response: alkaline phosphatase (ALP) below 1.67 times the upper limit of normal, at least a 15% reduction from baseline, and total bilirubin below the upper limit of normal.

At week 52, biochemical response occurred in 56.7% of saroglitazar-treated patients and 9.8% of placebo recipients (between-group difference, 48.0%; 95% CI, 35.3–60.8; p<0.001). ALP normalized in 8.2% versus 0% (p=0.016). Among patients with a baseline 5-D Itch score of at least 12, an improvement versus placebo was seen at week 24 but was not maintained at week 52. Adverse events occurred in 81.1% and 90.5%, respectively; serious adverse events occurred in 6.3% and 11.1%.

The findings support biochemical activity over 52 weeks in this population, but the primary endpoint is based on liver biochemistry, and the report does not establish effects on clinical outcomes. The results alone do not establish a change in treatment practice.

In practice

For patients with PBC who have an inadequate response to or cannot tolerate ursodeoxycholic acid, this 52-week randomized trial found a higher rate of biochemical response with saroglitazar than placebo. The result is based on liver biochemical measures; the report does not establish improvement in clinical outcomes, and ALP normalization was uncommon. Itch-score benefit in the subgroup with greater baseline itch was not maintained at week 52. These findings alone do not establish a change in treatment practice.

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Source

Hepatology: A phase 2b/3 trial of saroglitazar in primary biliary cholangitis ↗

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