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Pipeline update: 7 reports on autoimmune liver disease therapies

Autoimmune liver diseases include primary biliary cholangitis, primary sclerosing cholangitis, and pediatric diseases such as biliary atresia and progressive familial intrahepatic cholestasis. Researchers continue to investigate and develop potential treatments for both the diseases and their debilitating complications.

Healio Gastroenterology and Liver Disease present the following reports on therapy development including a bile acid inhibitor for pediatric PFIC, a treatment for PBC-related pruritus, a treatment for collagen improvement, and a therapy for bone mineral density in patients with PBC.

Maralixibat bile acid inhibitor enters phase 3 trial for pediatric PFIC

Mirum Pharmaceuticals dosed the first patient in a phase 3 trial of maralixibat, its lead drug candidate for the treatment of pediatric patients with progressive familial intrahepatic cholestasis, according to a press release.

“PFIC is a devastating condition that negatively affects children and their families,” Chris Peetz, president and CEO of Mirum, said in the release. “With no approved drug therapy, the start of the phase 3 MARCH-PFIC clinical trial is an important milestone for Mirum and puts us one step closer to potentially offering children a new treatment option that targets bile acid overload, a primary driver of liver damage and pruritus in this progressive disease.” Read more

Oral Korsuva enters phase 2 for treatment of PBC-related pruritus

Cara Therapeutics announced the initiation of a phase 2 trial of oral Korsuva for the treatment of pruritus in patients with hepatic impairment due to primary biliary cholangitis, according to a press release.

Korsuva (CR845/difelikefalin) is a first-in-class kappa opioid receptor agonist that targets the body’s peripheral nervous system and certain immune cells. The tablet formulation was engineered using Enteris BioPharma’s proprietary oral peptide delivery technology, Peptelligence. Read more

Denosumab increases bone mineral density in patients with PBC

Long-term treatment with denosumab increased bone mineral density without any adverse effects in patients with autoimmune liver disease, specifically primary biliary cholangitis, according to the results of a pilot study.

“Osteoporosis is a major complication in patients with primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH),” Yoshitaka Arase, MD, PhD, from the Tokai University School of Medicine in Japan, and colleagues wrote, with a nearly twofold increased risk compared with individuals without PBC. Read more

Entyvio reduces ALP in subset of patients with IBD, PSC

Study results showed that Entyvio decreased alkaline phosphatase serum levels by 20% in a subset of patients with concomitant inflammatory bowel disease and primary sclerosing cholangitis.

While Kate D. Lynch, MD, from the University of Oxford in the United Kingdom, and colleagues observed no evidence of a biochemical response to Entyvio (vedolizumab, Takeda Pharmaceuticals), treatment was well-tolerated, and the overall response was the same as expected for patients without PSC. Read more

Ocaliva associated with collagen improvement in patients with PBC

Post-hoc analysis of data from a POISE substudy has shown reduction in fibrosis “supporting the overall trend of improvement or no progression in the histologic components of PBC,” a rare autoimmune liver disease of intrahepatic bile ducts leading to progressive fibrosis and eventual cirrhosis, according to a researcher here.

“Measuring collagen content is emerging as a reliable method of quantifying liver fibrosis and has shown evidence of being an effective tool in [patients with] PBC,” said Paul Pockros, MD, speaking at Digestive Disease Week. Read more

Elafibranor shows anticholestatic effect in PBC

When patients do not fully respond to ursodeoxycholic acid, a new peroxisome proliferator-activated receptor alpha and delta agonist may offer control for alkaline phosphatase and may even alleviate pruritis, according to new data presented during the International Liver Congress.

“Both doses of elafibranor achieved the primary endpoint of alkaline phosphatase reduction; achieved key secondary composite endpoints aligned to future registrational studies; significantly reduced PBC-related cholestatic markers, IgM, HsCRP and bile acid precursors,” Velimir Luketic, MD, from Virginia Commonwealth University School of Medicine, said during his presentation. “Strong alkaline phosphatase and composite results further justify moving elafibranor into a phase 3 trial in PBC patients with inadequate response to UDCA. Read more

Givosiran offers hope for acute hepatic porphyria recurrent attacks

An “exciting, novel RNAi therapy” significantly lowered acute hepatic porphyria recurrent attacks, according to data presented during the International Liver Congress 2019.

“Fifty percent of the givosiran patients were attack-free for the 6-month study duration compared to 16.3% of the placebo-treated patients. This is a highly clinical endpoint and these patients were severely affected at baseline,” Manisha Balwani, MD, MS, of the Icahn School of Medicine at Mount Sinai, said during a press conference. Read more