Committee recommends seladelpar approval in EU for treating PBC
Oral therapy approved in US in August under brand name Livdelzi
A branch of the European Medicines Agency (EMA) has recommended that Gilead Sciences’ oral therapy seladelpar be approved in the European Union as a second-line treatment for certain adults with primary biliary cholangitis (PBC).
The recommendation, from the EMA’s Committee for Medicinal Products for Human Use, known as CHMP, specifically supports seladelpar’s clearance in combination with the first-line PBC therapy ursodeoxycholic acid, or UDCA. CHMP recommended the therapy’s approval as a combo treatment for PBC patients who don’t respond to UDCA alone, or for use on its own in those who are unable to tolerate UDCA.
The European Commission, which will make the final decision, isn’t required to abide by the committee’s recommendations, but almost always does. A decision from the commission is expected in the first months of 2025.
“We are encouraged by the CHMP’s positive opinion as we are one step closer to providing seladelpar to people living with PBC in Europe,” Timothy Watkins, MD, vice president of clinical development of inflammation therapeutics at Gilead, said in a company press release.
CHMP’s recommendation comes just a few months after seladelpar was granted accelerated approval in the U.S., where it is sold under the name Livdelzi. Gilead said it is also working on marketing applications for seladelpar in other parts of the world.
Palak Trivedi, MD, PhD, an associate professor and consultant hepatologist at the Queen Elizabeth Hospital in the U.K., called the committee’s recommendation “a significant milestone for the PBC community,” adding that seladelpar is “a potential new therapy that can help treat both the disease and improve symptoms that impact quality of life” among patients.
“After many years of treating people with PBC, I have seen the critical unmet need for additional effective and symptom-directed treatment options,” Trivedi said.
CHMP’s positive opinion on seladelpar based mainly on Phase 3 trial data
PBC is an autoimmune disease marked by inflammation in the bile ducts, which are a series of tubes that normally carry the digestive fluid bile out of the liver, where it’s made, and to the intestines.
Bile duct inflammation, called cholangitis, can disrupt normal bile flow, resulting in liver damage and bile leakage into the bloodstream. In patients, this causes symptoms such as itching.
UDCA, sold as Urso and Actigall in the U.S., is the first-line treatment for PBC. However, it doesn’t work for everyone and some patients can’t tolerate it. Up until earlier this month, Ocaliva (obeticholic acid) was available in the European Union as a second-line PBC therapy for patients not responding to UDCA. It also was not effective for all patients, however, and could even worsen itching in some cases.
Watkins noted that “there are still people living with PBC who do not have an adequate response to current medicines or who are still experiencing symptoms, such as debilitating itch.”
For these patients, “Gilead is committed to bringing forth therapies that not only improve markers of disease progression but also help alleviate symptoms,” Watkins said.
Seladelpar, taken as an oral capsule once a day, works by selectively activating PPAR-delta, a protein that controls the activity of certain genes involved in liver inflammation, scarring, and bile production. As such, the therapy is expected to slow or prevent further liver damage and ease symptoms in PBC patients.
The CHMP’s positive opinion on seladelpar was based mainly on data from a Phase 3 clinical study called RESPONSE (NCT04620733), which compared the therapy against a placebo in PBC patients who didn’t respond to or couldn’t tolerate UDCA.
The results indicated that seladelpar was significantly better than the placebo at normalizing markers of liver damage after one year.
This positive opinion from the committee confirms [the] promising clinical benefit and value of seladelpar, which has been underscored by its differentiated body of data.
In the study, more than 60% of seladelpar-treated patients achieved the main goal of showing normalization or near normalization of two liver damage markers, alkaline phosphatase and bilirubin. Among participants given the placebo, that goal was achieved by 20%.
Further, 1 in 4 patients on seladelpar, but none in the placebo group, achieved alkaline phosphatase normalization after one year. The therapy also was significantly superior to the placebo at relieving itch within six months of treatment.
According to Trivedi, “this positive opinion from the committee confirms [the] promising clinical benefit and value of seladelpar, which has been underscored by its differentiated body of data.”
An ongoing Phase 3 clinical trial, dubbed AFFIRM (NCT06051617), is now testing whether seladelpar is better than a placebo at improving clinical outcomes in adults with PBC. That study is enrolling an estimated 192 PBC patients with compensated cirrhosis — where the liver can still work despite some degree of irreversible liver scarring. It may still be recruiting patients at sites in the U.S., Turkey, and South Korea.
The study’s main goal is to assess how long patients live without liver-related events, such as liver disease worsening, hospitalizations, and liver transplant, over three years.
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