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Positive Topline Results for New NASH Drug

The results are consistent with the original analysis from 2019, where the treatment resulted in a statistically significant effect on fibrosis improvement.

New topline results show obeticholic acid (OCA) has a positive impact on patients with liver fibrosis because of nonalcoholic steatohepatitis (NASH).

The results, announced by Intercept Pharmaceuticals, come from the ongoing phase 3 REGENERATE trial and are the second analysis where the treatment met the primary endpoint for the intent-to-treat population.

REGENERATE Trial

In the 931 patient study, investigators found 22.4% of patients randomized to once-daily oral OCA 25 mg met the primary endpoint of achieving at least 1 stage of fibrosis improvement with no worsening of NASH at month 18 on liver biopsy compared to 9.6% of the placebo group (P <0.0001).

The results are consistent with the original analysis from 2019, where the treatment resulted in a statistically significant effect on fibrosis improvement (P = 0.0002).

One difference, however, is the investigators used a consensus panel approach to histology reads, which is consistent with recent US Food and Drug Administration guidance, compared to results from individual central readers in the original analysis.

The positive results also show more individuals in the treatment group achieved the endpoint of resolution of NASH with no worsening of liver fibrosis compared to placebo. However, these results did not reach statistical significance.

Safety

In the safety analysis, the investigators used data from 2477 participants who took at least dose of the study drug—either placebo, OCA 10 mg, or OCA 25 mg.

The newer analysis also had significantly longer exposure to the study drug, 42 months compared to 15 months, with almost 1000 participants on the study drug for 4 years.. This resulted in more than 8000 total patient-years and 3.4 times more exposure.

Treatment-emergent adverse events, treatment-emergent serious adverse events, and deaths were balanced across both the treatment groups and the placebo group.

The most common adverse event was pruritus (24% in placebo, 33% in OCA 10 mg and 55% in OCA 25 mg), which was also the most common cause for treatment discontinuation.

Serious gallbladder-related events occurred in the less than 3% of the patient population, which is consistent with the known mechanism of action of OCA.

The analysis also included a blinded adjudication of safety events by independent groups of experts, as requested by the FDA. This included events on hepatic safety, cardiovascular, and renal outcomes.

There was a numerically higher number of adjudicated hepatic safety events in the OCA 25 mg group, the majority of which were mild in severity.

There was low frequency of core adjudicated major adverse cardiovascular events and adjudicated acute kidney injury events.

OCA was also associated with an increase in LDL in month 1, which is consistent with the mechanism of action of FXR agonists. However, the LDL returned to baseline values at month 12.

There were changes in other blood chemistries, including alkaline phosphatase, gamma-glutamyl transferee, aspartate aminotransferase, alanine aminotransferase showed evidence of FXR mediated activity.

“Achieving a statistically significant histology endpoint has proven to be an extremely high bar in clinical trials for NASH,” said Jerry Durso, President and Chief Executive Officer of Intercept, in a statement. “These results demonstrate the antifibrotic effect of OCA and are consistent with our belief that OCA can be an important treatment for people living with fibrosis due to NASH.

“The weight of evidence in both safety and efficacy has notably increased and provides a more robust benefit:risk profile of OCA,” he added.

Intercept also said they will be submitting a New Drug Application for this indication in the future.