Iqirvo approved in UK for adults with PBC, problems with UDCA
NICE expected to decide on public funding for new therapy by year's end
U.K. regulators have approved Iqirvo (elafibranor) for adults with primary biliary cholangitis (PBC) who fail to respond to or cannot tolerate first-line disease treatment with ursodeoxycholic acid (UDCA).
The decision by the U.K.’s Medicines and Healthcare products Regulatory Agency (MHRA) follows similar approvals in the U.S. and European Union earlier this year. All were backed by data from the ongoing Phase 3 ELATIVE clinical trial (NCT04526665), where Iqirvo was found to outperform a placebo at reducing blood biomarkers of liver damage.
In all of these regions, Iqirvo, marketed by Ipsen, is being given as a once daily 80 mg oral tablet taken either in combination with UDCA for patients who had an inadequate response to the first-line therapy, or alone for those who didn’t tolerate it.
UDCA is a first-line treatment for PBC, but not all patients can use it
“Enabling safe access to high quality, safe and effective medicines is a key priority for us,” Julian Beach, MHRA’s interim executive director of healthcare quality and access, said in an agency press release. “We’re assured that the appropriate regulatory standards of safety, quality and effectiveness for the approval of this new formulation have been met.”
England’s National Institute for Health and Care Excellence, or NICE, is reviewing the treatment to decide whether it will be covered under the country’s publicly funded National Health Service. Coverage would mean that eligible patients could access the therapy at little to no cost, and a decision is expected by year’s end.
PBC is a chronic form of cholangitis, a condition marked by inflammation in the bile ducts, the network of tubes that transport the digestive fluid bile from the liver to the intestines, ultimately damaging them.
As a result, bile accumulates in the liver, driving its damage and dysfunction, as well as in the bloodstream, leading to PBC symptoms such as itchy skin or pruritus.
First-line treatment with UDCA, sold under the brand names Urso and Actigall, doesn’t fully control PBC for all patients, and can lead to intolerable side effects for others.
Iqirvo is designed to activate PPAR alpha and PPAR delta, two receptor proteins believed to be involved in regulating cellular processes implicated in PBC, including inflammation, scarring, and the production of bile components.
By activating them, Iqirvo aims to keep these processes under control and ease disease symptoms.
Phase 3 trial found Iqirvo helped to normalize liver damage markers in patients
The global ELATIVE study enrolled 161 adults with PBC and inadequate or intolerable responses to UDCA, who were randomly assigned to either Iqirvo (80 mg) or a placebo tablet once daily for at least a year.
Top-line results showed that a significantly higher proportion of treated patients experienced a normalization of two biomarkers of liver damage, alkaline phosphatase (ALP) and bilirubin, relative to a placebo after a year (51% vs. 4%), meeting the study’s main goal.
Measures of itching and life quality also tended to favor Iqirvo over a placebo, and the treatment was generally well tolerated.
Participants who completed the main placebo-controlled study were able to enter the its open-label extension, where all are receiving Iqirvo for up to five years. The extension trial is due to finish in 2028.
Other ongoing clinical trials are expected to help confirm the benefits of Iqirvo in PBC.
One is the Phase 3 ELFIDENCE study (NCT06016842), which is looking into how Iqirvo influences long-term liver health and survival in adults with PBC. ELFIDENCE is recruiting participants at sites in the U.S., Europe, and South Korea, while a site in New Zealand also may open.
Ongoing trials include evaluating therapy in a real-world setting
Other active Ipsen-sponsored studies include the Phase 3 ELSPIRE trial (NCT06383403) and the observational study called ELFINITY (NCT06447168).
ELSPIRE, which is actively recruiting at a site in Texas — with additional sites in the U.S., Europe, and South Korea due to open — mainly is assessing the treatment’s ability to lower ALP levels. ELFINITY, which is seeking participants at two U.S. sites, is evaluating the effects of Iqirvo in a real-world treatment setting.
Meanwhile, the fully enrolled Phase 2 ELMWOOD trial (NCT05627362) is testing Iqirvo against a placebo in adults with primary sclerosing cholangitis, another chronic form of cholangitis.
“There are many people living with PBC with their needs unmet — be that markers of their disease worsening or symptom burden not being controlled. This can have profound implications for patients and their families, which is why a new treatment option is so vitally important,” Mo Christie, head of patient services for the U.K.’s PBC Foundation, said in an Ipsen press release.
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