A new era for PBC treatment: Expert insights on existing, emerging therapies
Key takeaways:
- Long-term studies of PBC treatments show promising efficacy and safety data.
- Intestinal bile acid transport inhibitors show promise for pediatric cholestatic conditions.
Primary biliary cholangitis poses a significant challenge in hepatology, necessitating effective treatment strategies to improve patient outcomes and quality of life.
In a recent interview, James Boyer, MD, FRCP, Ensign Professor of Medicine and emeritus director of the Liver Center at Yale School of Medicine, provided valuable insights into the evolving landscape of primary biliary cholangitis (PBC) therapeutics, emphasizing both established treatments and promising innovations.
Current therapies
Currently, therapies for biliary liver diseases such as PBC and primary sclerosing cholangitis (PSC) include Ocaliva (obeticholic acid, Intercept Pharmaceuticals) and ursodeoxycholic acid, or ursodiol. Boyer underscored the safety and efficacy of these treatments, noting their role in improving transplant-free survival rates.
“There has been a long-term, 6-year, open-label study for Ocaliva, which showed reduction in death and transplant-free survival of about 70%,” he said.
Boyer also cited two real-world studies, one that enrolled patients from the global PBC cohort and another conducted in the U.K., which demonstrated Ocaliva efficacy. According to results of the 6-year study, Ocaliva had a significantly greater transplant-free survival compared with external control patients.
There are inherent challenges in long-term studies such as this, Boyer acknowledged, particularly regarding patient dropout rates. “Unfortunately, in a study like this, many patients drop off in the long-term protocols, because they find out they’re in the placebo group,” he said.
Emerging therapies
Turning to emerging therapeutics, Boyer noted “promising” data from the phase 2a INTEGRIS-PSC trial, which found that bexotegrast 320 mg reduced liver fibrosis markers compared with placebo at week 12, and also showed improvements via liver imaging. “They’ve measured serum markers of fibrosis including ELF, procollagen 3 peptide and liver biochemistries that have all been significantly improved by the drug,” he said.
Pediatric advancements
Boyer also addressed therapies tailored for pediatric patients. “There are also new drugs for the pediatric group called intestinal bile acid transport inhibitors,” he said, referencing recent FDA approvals for conditions like Alagille syndrome and progressive familial intrahepatic cholestasis.
While trials are ongoing for adult cholestatic diseases, Boyer emphasized the potential of these inhibitors in addressing pediatric cholestatic conditions.
One of the challenges in treating biliary liver diseases is providing updated information to primary care providers, he said. “There is not a lot of knowledge, particularly about these new developments.”
References:
- Floreani, A, et al. Biomedicines. 2022;doi:10.3390/biomedicines10102464.
- Pliant Therapeutics announces positive safety and exploratory efficacy data from the INTEGRIS-PSC phase 2a trial of bexotegrast 320 mg in patients with primary sclerosing cholangitis and suspected liver fibrosis. https://ir.pliantrx.com/news-releases/news-release-details/pliant-therapeutics-announces-positive-safety-and-exploratory-0. Published Feb. 4, 2024. Accessed Feb. 27, 2024.
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