FDA approves Gilead’s Livdelzi for treatment of primary biliary cholangitis
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Gilead’s Livdelzi, a selective peroxisome proliferator-activated receptor delta agonist, has received accelerated FDA approval for the treatment of primary biliary cholangitis, according to a company release.
Livdelzi (seladelpar) was approved for use in combination with ursodeoxycholic acid (UDCA) in adult patients who did not adequately respond to UDCA or as monotherapy for those who are intolerant to UDCA.
“People living with PBC have been waiting for treatment advancements for many years. Today’s approval of Livdelzi, with its distinct profile, provides them with an important new option,” Daniel O’Day, Gilead’s chairman and CEO, said in the release. “We look forward to leveraging Gilead’s longstanding expertise in liver disease to bring this promising new treatment to all those who could benefit.”
The FDA based its decision on a reduction in alkaline phosphatase (ALP), a key result from the placebo-controlled, phase 3 RESPONSE study, which compared once-daily Livdelzi 10 mg (n = 128) with placebo (n = 65) for 12 months.
According to RESPONSE results, 62% of patients treated with Livdelzi vs. 20% with placebo achieved the primary endpoint of composite biochemical response at month 12, defined by a reduction in ALP (< 1.67-times the upper limit of normal with at least a 15% reduction from baseline) and total bilirubin ( upper limit of normal). In addition, 25% of patients receiving Livdelzi achieved normalization of ALP values at this timepoint, which was not observed in patients receiving placebo.
Further, at 6 months, those treated with Livdelzi showed a “statistically significant reduction in pruritus,” the release stated.
Common adverse events reported in at least 5% of patients treated with Livdelzi included headache, abdominal pain, nausea, abdominal distension and dizziness; however, no treatment-related serious adverse events were reported.
Livdelzi is solely indicated for the treatment of PBC, based on a reduction in ALP, and improvement in survival or prevention of liver decompensation events has not been reported. Continued approval for this indication “may be contingent on verification and description of clinical benefit in confirmatory trial(s),” the release stated.
Gilead’s commitment to the ongoing, confirmatory AFFIRM study, a randomized, placebo-controlled, phase 3 study assessing the impact of Livdelzi on patients with compensated cirrhosis related to PBC, is part of the FDA’s accelerated approval.
“More people are being diagnosed with PBC, impacting people of varied ages, gender, race and ethnicity,” Carol Roberts, president of the PBCers Organization, said in the release. “Those living with PBC share common symptoms, including incessant itching or skin-crawling sensations, as well as debilitating fatigue that is made worse by the itching at night. The availability of a new treatment option that can help reduce this intense itching while also improving biomarkers of active liver disease is a milestone for our community.”
According to the release, Livdelzi is not recommended for patients who have or develop decompensated cirrhosis.
Perspective
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Dian-Jung Chiang, MD, MPH
The accelerated FDA approval of seladelpar as a second-line agent for PBC is long-awaited news for many patients, as well as physicians treating this chronic illness.
It is estimated that up to 40% of PBC patients do not achieve adequate response with first-line UDCA, and only up to 47% of those non-responders respond to the currently available second-line agent, obeticholic acid. Therefore, many PBC patients do not have alternative treatment options.
Despite promising results from the RESPONSE trial and FDA approval of seladelpar, it is worth noting that we do not yet have data on whether seladelpar could improve liver fibrosis stage, prevent cirrhosis or reduce mortality. Longer-term follow-up studies will be necessary to help us answer this.
Perspective
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Gideon Hirschfield, PhD
With the FDA approval of Livdelzi, people with PBC have good reason to be excited about future treatment options available to them.
Livdelzi is a drug now proven to be effective at improving both the biochemical disease activity of PBC and, equally important, itch — a key symptom reducing quality of life.
The pivotal phase 3 trial showed that at a dose of 10 mg daily, Livdelzi led to normalization of ALP — a key PBC biomarker — in one in four patients after only 12 months of therapy. Clinically significant reductions in pruritus also were abundantly clear.
Per the FDA label, the drug safety profile appears good, and there are already publications on long-term use, demonstrating ongoing sustained and continually improving biochemical response rates to therapy. It is not surprising that those living with PBC are excited about the prospect of this new therapy changing the course of their disease and improving their quality of life.
I am sure the gastroenterology and hepatology communities will welcome this new addition to the therapy we can offer our patients, as we strive toward the goal of treating patients with PBC as individuals, aiming for normal tests and normal quality of life.
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