SAN DIEGO—The newly approved drug seladelpar was found to be safe and effective in treating patients with both primary biliary cholangitis and cirrhosis, in a new analysis of results from the phase 3 RESPONSE study presented at The Liver Meeting 2024.
Seladelpar (Livdelzi, Gilead)—a peroxisome proliferator–activated receptor gamma agonist granted accelerated approved by the FDA in August—led to decreases in markers of cholestatic and liver injury, and its adverse effects profile was similar to that of placebo in patients with and without cirrhosis, reported investigator Alejandra Villamil, MD, the chief of the autoimmune liver diseases unit at Hospital Italiano de Buenos Aires, in Argentina.
The RESPONSE study included 193 patients with incomplete response to ursodeoxycholic acid who were randomized 2:1 to receive seladelpar (10 mg) or placebo (abstract 0164). Cirrhosis was present at baseline in 27 patients, including 18 in the treatment group and nine in the placebo group.
The researchers noted similar changes in alkaline phosphatase and alanine aminotransferase at 12 months in patients with cirrhosis and those without cirrhosis (Table). Total bilirubin remained stable in both groups, and liver stiffness remained generally stable among patients with cirrhosis in both the treatment and placebo groups over the 12-month study period, Dr. Villamil said.
| Table. Changes From Baseline in Outcome Markers | ||||
| Marker | Patients with cirrhosis | Patients without cirrhosis | ||
|---|---|---|---|---|
| Seladelpar | Placebo | Seladelpar | Placebo | |
| Alkaline phosphatase, U/L | –121.4 | 23.2 | –134.8 | –18.0 |
| Alanine aminotransferase, U/L | –5.1 | 1.9 | –4.7 | –12.9 |
| Based on TLM 2024 abstract 0164. | ||||
The drug also was found to be safe, he added. “Adverse events … in patients with cirrhosis that were exposed to seladelpar were similar to the rest of the population. No treatment-related events were seen, and among [cirrhotic patients], there was no adverse event that [led] to treatment discontinuation or study discontinuation.”
“I think it’s really valuable to have included cirrhotic patients in the study because … they are often excluded in the initial phases of studies because of the risk of complications,” said Vania Kasper, MD, an associate professor of pediatrics at Brown University Health, in Providence, R.I., who co-moderated the session in which Dr. Villamil presented the findings. “Knowing that you can use these medications to have a significant improvement in quality of life is a very important point to establish.”
Co-moderator Yury Popov, MD, PhD, also underscored the value of studying patients with cirrhosis. “This is actually extremely important—to study all the drugs that we develop in the most advanced patients … because at the end of the day, what we want to achieve with therapy is that the most desperate and the most severe patients are responding.”
Dr. Popov, who is an associate professor of medicine at Beth Israel Deaconess Medical Center, in Boston, explained that because clinical trials are very often designed to study efficacy in the most precise way possible, “typically, patients with cirrhosis are excluded” due to risks that may undermine the study’s validity and conclusions. “So that I thought was great,” he added. “I wish maybe it was pushed even further with decompensation or varices included in the studies, because these are the patients that have the least amount of options and they would benefit the most [from effective therapy].”
—Jim Kling
Dr. Kasper reported no relevant financial disclosures. Dr. Popov reported financial relationships with Enveda, Mediar, Morphic, RNAV8 Bio and Takeda. Dr. Villamil reported financial relationships with Intercept and Novartis.
This article is from the May 2025 print issue.