Seladelpar conditionally approved in European Union to help treat PBC
Can be used with UDCA or alone for those unable to tolerate first-line therapy
Gilead Sciences’ oral therapy seladelpar has been conditionally approved by the European Commission as a second-line therapy for adults with primary biliary cholangitis (PBC).
It is cleared for use in combination with ursodeoxycholic acid (UDCA), a first-line PBC therapy, in patients who haven’t responded well to UDCA on its own, and as a monotherapy for those who can’t tolerate UDCA.
The approval, which comes a few months after it was recommended by a committee of the European Medicines Agency, draws on data from RESPONSE (NCT04620733), a Phase 3 clinical trial in which seladelpar outperformed a placebo at reducing liver damage markers and itching (pruritus).
“People living with PBC in Europe have been waiting for treatment advancements for many years,” Timothy Watkins, MD, vice president of clinical development of inflammation therapeutics at Gilead, said in a company press release. “We look forward to working with health authorities across Europe to bring this promising new treatment to all those who could benefit.”
‘Important new treatment option’ for select adults with PBC in Europe
“Today’s decision reinforces the clinical benefit and value of seladelpar and offers people living with PBC in Europe an important new treatment option,” said María-Carlota Londoño, MD, PhD, a hepatologist at Hospital Clínic Barcelona and associate professor at the University of Barcelona, in Spain.
Seladelpar was given accelerated approval in the U.S. for the same indication in 2024, and is marketed there under the brand name Livdelzi. Conditional, or accelerated, approvals make experimental therapies available based on preliminary evidence of efficacy and safety, with full approval being dependent on further trial data confirming those findings.
Livdelzi also was approved in the U.K. for these same patient groups earlier this year. The therapy is under review by regulators in Canada and Australia, according to the company.
PBC is a form of cholangitis, or inflammation of the bile ducts that carry bile, a digestive fluid, from the liver into the small intestine to help in digestion. Over time, inflammation can damage the bile ducts and cause bile to build to toxic levels in the liver and leak into circulating blood, leading to pruritus and other disease symptoms.
UDCA, marketed under the brand names Actigall and Urso in the U.S. and available as generics, is the first-line PBC therapy. However, many patients fail to respond adequately to UDCA and need a second-line treatment to prevent the disease from progressing.
“There are people in Europe who do not have an adequate response to first-line therapy and seladelpar helps address the unmet need for effective and symptom-directed treatment,” said Londoño, a member of Gilead’s scientific review committee for a research scholars program in the field of PBC.
Biochemical responses to seladelpar evident in pivotal Phase 3 trial
Available as an oral capsule, seladelpar works by activating a protein called PPAR-delta, which helps to control the production of bile acids, the main component of bile. By activating PPAR-delta, seladelpar reduces the production of bile acids in the liver, which is expected to reduce inflammation and ease disease symptoms.
The global and pivotal RESPONSE trial tested how daily dosing with seladelpar compared with a placebo over 12 months, or about a year, in 193 adults with PBC didn’t fully respond to or couldn’t tolerate UDCA.
A significantly greater percentage of patients were reported to achieve a biochemical response with seladelpar than with a placebo (61.7% vs. 20%), based on reductions in blood levels of alkaline phosphatase and bilirubin, two biomarkers of liver damage. Alkaline phosphatase reached normal levels in 25% of patients given seladelpar and in no patient on a placebo.
Patients reported degrees of relief from itching with oral therapy’s use
Daily seladelpar treatment also significantly reduced pruritus compared with a placebo. After six months, people with moderate to severe itching at study’s start experienced a 3.2-point drop, on a zero to 10 scale, with seladelpar, indicating less itching. Those on a placebo had a 1.7-point reduction.
Slightly more than one-quarter of patients with moderate itching (26.5%) and 18.8% of those with more severe itching at study’s start also reported near total relief after one year of treatment.
The most commonly reported adverse events with seladelpar during clinical testing were headache, nausea, and a painful or distended abdomen.
Gilead is working to make the oral therapy quickly available to eligible patients living in the European Economic Area, which includes European Union (EU) member countries as well as Iceland, Liechtenstein, and Norway, it stated.
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