Gilead’s Livdelzi (Seladelpar) for Primary Biliary Cholangitis Promises Pruritus Reduction

The US Food and Drug Administration (FDA) has given the nod to Livdelzi (seladelpar) for treating primary biliary cholangitis (PBC), a rare autoimmune disease that primarily affects women.

PBC gradually destroys the bile ducts in the liver, leading to inflammation, scarring and, if untreated, potentially liver failure. For the 130,000 Americans living with this condition, many find existing treatments either ineffective or hard to tolerate.

Livdelzi is now the second peroxisome proliferator activated receptor (PPAR) delta agonist (delpar) approved for PBC, following closely on the heels of Iqirvo (elafibranor), which recently became a first-in-class drug for PBC.

Livdelzi is available in once daily, 10 mg oral capsules. However, it is not recommended for patients with decompensated cirrhosis.

PPAR agonists have shown high potential in PBC treatment and diabetes research, particularly for their anti-inflammatory and metabolic effects, which not only improve symptoms but also enhance quality of life. PPAR drugs have been shown to alleviate pruritus, a debilitating itch that develops in up to 70 percent of PBC patients.

In the RESPONSE clinical trial, 62 percent of participants taking seladelpar showed significant improvements in liver function after 12 months, compared to just 20 percent in the placebo group. A key result was the normalization of alkaline phosphatase (ALP) — a vital liver enzyme — in 25 percent of patients treated with seladelpar, a result not seen in the placebo group.

Additionally, the drug significantly reduced pruritus, the relentless itching that plagues many PBC patients, with improvements observed as early as six months into treatment.

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With no cure currently available, treatments like Livdelzi and Iqirvo are crucial in managing PBC and improving patients’ symptoms and thereby, quality of life.

In clinical trials, Livdelzi stood out for its strong impact on reducing pruritus and normalizing ALP levels, whereas Iqirvo, with its dual PPAR-alpha and PPAR-delta activation, focused on ALP reduction and enhancing liver function.

Further support for Livdelzi’s efficacy comes from other studies, including the long-term open-label ASSURE study and earlier trials, involving over 500 participants. The drug has been consistently shown to reduce key biomarkers of PBC, with durable improvements in both pruritus and cholestasis markers, which are linked to disease progression.

Livdelzi is the first drug in Gilead’s inflammatory diseases pipeline to receive FDA approval this year. The ongoing Phase III AFFIRM study, will be evaluating Livdelzi’s impact on clinical outcomes in people with compensated cirrhosis due to PBC.