Zydus Therapeutics has reported a numerically higher biochemical response to its investigational drug saroglitazar among US patients with primary biliary cholangitis (PBC) than among patients enrolled outside the United States.

 

According to a new analysis of its pivotal EPICS-III clinical trial, a treatment difference of 60.7 percentage points between saroglitazar and placebo was found in the US subgroup, compared with 41.6 percentage points in the non-US subgroup.

 

Saroglitazar is an investigational drug that has not been approved by the US FDA. Its safety and effectiveness have not been established.

 

The findings add to the clinical data on saroglitazar for adults with PBC who have an inadequate response to, or cannot tolerate, ursodeoxycholic acid (UDCA), a standard treatment for the disease.

 

The analysis compared 28 patients receiving saroglitazar with 14 receiving placebo in the US subgroup. The non-US group, comprising patients from Argentina, Iceland and Turkey, included 69 patients treated with saroglitazar and 37 receiving placebo.

 

Composite biochemical response rates were 60.7% among US patients receiving saroglitazar, against 0% among those receiving placebo. In the non-US subgroup, the corresponding rates were 55.1% and 13.5%.

 

Although the treatment difference was numerically greater in the US subgroup, the analysis was exploratory and post hoc. The findings should therefore be interpreted with caution and do not establish that the drug works better in US patients.

 

The analysis also assessed changes in alkaline phosphatase (ALP), a key biochemical marker of PBC. At Week 52, ALP normalization treatment differences were broadly similar between the US and non-US subgroups, at 7.7 and 9.6 percentage points, respectively.

 

ALP reductions from baseline were numerically greater with saroglitazar than placebo in both groups. The treatment difference was -166.2 U/L in the US subgroup, compared with -104.7 U/L in the non-US subgroup.

 

Raj Vuppalanchi, Professor of Medicine at Indiana University School of Medicine and global principal investigator of EPICS-III, hailed the findings.

 

“These findings provide additional insight into the Phase 3 EPICS-III results and the biochemical responses observed among patients enrolled in different geographic regions,” said Raj Vuppalanchi. “While this was a post hoc analysis and the findings should be interpreted accordingly, we believe it is important to continue evaluating the EPICS-III data to better understand the results across the study population.”

 

Zydus said saroglitazar was generally well tolerated in the EPICS-III trial, with adverse events generally balanced between patients receiving the drug and those receiving placebo. The most common adverse reactions among saroglitazar-treated patients were pruritus, headache and urinary tract infection.