New Primary Biliary Cholangitis Treatments: What Patients and Payers Need to Know
By Emily Crisano, PharmD, and Jason Peterson, RPh
Primary biliary cholangitis (PBC) is a slow-progressing autoimmune disease that often goes undetected until liver damage has already occurred. For years, treatment options have been limited, but two new therapies approved this year—Iqirvo (elafibranor) and Livdelzi (seladelpar)—are offering new hope for patients by allowing for earlier intervention and improved outcomes.
Let’s take a closer look at what these new therapies mean for the future of PBC treatment and the evolving decisions around patient care and coverage.
What is PBC?
PBC is an autoimmune disease in which the body continuously attacks its own bile ducts within the liver. Bile ducts are essential for transporting bile from the liver and gallbladder to the small intestine, aiding in fat digestion. The destruction of these ducts leads to chronic cholestasis (a decrease or obstruction in bile flow) and eventually, cirrhosis (or severe scarring) of the liver. While cirrhosis is often linked to alcohol consumption, there is not a connection between PBC and alcohol.
The exact cause of PBC is unknown, but both genetic and environmental factors are believed to contribute to its development. PBC affects nearly 130,000 individuals in the U.S., primarily women ages 30 to 65. Nearly half of patients are identified due to liver test abnormalities rather than clinical symptoms. The asymptomatic nature of PBC complicates diagnosis and potentially leads to an underreporting of cases.
For symptomatic patients, common signs often include fatigue and itching. Other symptoms can include dry skin, patches of darkened skin, jaundice, dry eyes and mouth, high cholesterol, fatty deposits under the skin and abdominal pain. These symptoms indicate liver injury due to the destruction and impairment of the bile flow in PBC.
Diagnosis follows the 2021 American Association for the Study of Liver Diseases (AASLD) guidelines, which require the absence of extrahepatic biliary obstruction and liver-affecting comorbidities, and at least two of the following:
Alkaline phosphatase (ALP) at least 1.5 times the upper limit of normal
Presence of antimitochondrial antibodies (AMA) at a titer of 1:40 or higher
Histologic evidence of PBC from a liver biopsy
Current Treatments
PBC is a chronic disease that typically requires lifelong therapy once diagnosed. The primary goal of treatment is to slow down the destruction of the bile ducts and manage complications from cholestasis.
Ursodiol (also known as ursodeoxycholic acid or UDCA) is the first-line treatment, dosed based on the patient’s weight and taken orally twice daily. Liver test improvements can often be seen within the first three months of starting UDCA, though symptoms like fatigue and itchiness may persist.
If no significant improvement is observed after the first 12 months of taking UDCA, Ocaliva (also known as obeticholic acid or OCA) is often the next treatment option. OCA was approved through the accelerated pathway in 2016 and is expected to gain full FDA approval later this year. Many patients experience improvements after six months of taking OCA, but the treatment is contraindicated for those with cirrhosis and portal hypertension due to risks of cirrhosis. Because PBC is a lifelong disease that leads to the development of this type of liver decompensation, patients on OCA require close monitoring to track disease progression.
New Treatments
In the third quarter of this year, the FDA approved two new agents for PBC treatment Iqirvo (elafibranor) and Livdelzi (seladelpar), both peroxisome proliferator-activated receptor (PPAR) agonists.
Iqirvo
Iqirvo, created by Ipsen Biopharmaceuticals, was granted accelerated approval in June 2024. Iqirvo can be used in combination with ursodiol in adults who have had an inadequate response to ursodiol, or as monotherapy in patients unable to tolerate ursodiol. Data from the Phase 3 ELATIVE trial demonstrated Iqirvo’s ability to significantly reduce the alkaline phosphatase (ALP; a liver enzyme) compared to placebo without worsening the itching symptoms. Iqirvo has a reported wholesale acquisition cost (WAC) of $139,430 annually.
Livdelzi
Livdelzi, created by Gilead and approved by the FDA in August 2024, is also oral treatment to be used in combination with ursodiol in adults who have an inadequate response to ursodiol or as monotherapy in those unable to tolerate ursodiol. Livdelzi received accelerated approval based on data from the Phase 3 RESPONSE study in which patients treated with Livdelzi achieved a reduction in their ALP and total bilirubin (another liver measurement test) compared to placebo. Livdelzi has an estimated WAC of $153,373 annually.
While Ocaliva remains a second-line treatment, some patients may transition to these new drugs earlier in their disease progression.
Confirmatory trials are needed for Iqirvo and Livdelzi to understand their effectiveness in patients who have or develop cirrhosis during their course of their disease. Notably, neither Iqirvo nor Livdelzi has been linked to worsening itching, a major symptom for many PBC patients—and Livdelzi in particular showed improvements in itching during trials.
With Gilead’s established expertise in hepatology, it is likely that Livdelzi will gain market preference over Iqirvo. Providers may also gravitate to Livdelzi based on the trial result of a decrease in their itching scores. Ongoing confirmatory trials for all three agents will ultimately shape clinical and payer decisions.
What New Treatments Mean for Payers
These newer therapies, while providing promising patient outcomes, come with significantly higher costs than traditional treatments like ursodiol. As a result, payers will need to carefully evaluate how to integrate these options into a coverage plan.
Step therapy will likely be a key strategy, requiring patients to first try lower-cost treatments like ursodiol before moving onto these more costly medications. That being said, payers must also consider the clinical benefits of earlier intervention with these Iqirvo and Livdelzi. By delaying disease progression, these treatments may reduce long-term healthcare costs related to liver failure, transplants or complications from cirrhosis.
In addition, the ongoing need for confirmatory trials to fully understand the long-term effectiveness and safety of Iqirvo and Livdelzi patients with advanced PBC will play a role in payer-decision-making. As more data emerges, payers will be able to refine coverage policies to ensure the best outcomes for patients while managing costs.
Moving Forward
The approval of Iqirvo and Livdelzi represents a major shift in the way PBC is treated, offering patients more hope for earlier intervention and better long-term outcomes. As research continues and more data becomes available, the ability to personalize treatment for PBC will improve, helping both patients and healthcare providers manage this challenging disease more effectively.
The focus now shifts to ensuring these promising therapies are accessible to those who need them most, paving the way for better outcomes and a more sustainable approach to long-term care.