FDA Grants Accelerated Approval to Seladelpar: A New Chapter in Primary Biliary Cholangitis Treatment

The First Drug to Show Statistically Significant Improvements Across Multiple Disease Markers

Gilead Sciences announced a major milestone today with FDA accelerated approval for seladelpar (marketed as Livdelzi), an oral medication designed to treat primary biliary cholangitis (PBC). This marks a significant breakthrough for a condition that has long lacked effective treatment options, particularly for patients who don’t respond adequately to existing therapies.

What Makes This Approval Stand Out?

The approval is grounded in compelling clinical data from the Phase 3 RESPONSE study. Here’s where seladelpar demonstrated its distinct advantage:

Biochemical Response Rates: Among patients taking seladelpar, 62% achieved composite biochemical response at 12 months, compared to just 20% of those on placebo. This threefold difference represents a substantial therapeutic advancement.

ALP Normalization—A Game-Changer: Alkaline phosphatase (ALP) normalization occurred in 25% of seladelpar-treated patients, with zero patients in the placebo group achieving this outcome. This is particularly significant because ALP levels serve as a predictor of liver transplant risk and mortality in PBC patients.

Pruritus Relief: Chronic itching is one of the most debilitating symptoms of PBC, often disrupting sleep and quality of life. Seladelpar demonstrated statistically significant reductions in pruritus symptoms at six months—an outcome placebo could not match.

Why This Matters for Patients

PBC affects approximately 130,000 Americans, predominantly women. The disease is autoimmune in nature, causing progressive bile duct destruction and potential liver failure if left unmanaged. Until now, many patients faced inadequate response to ursodeoxycholic acid (UDCA), the standard treatment, leaving them at continued risk for liver damage.

Seladelpar operates as a peroxisome proliferator activated receptor (PPAR) delta agonist, targeting metabolic and liver disease pathways that UDCA alone cannot address. This distinct mechanism positions it to fill a genuine treatment gap for therapy-resistant patients.

The Clinical Landscape

The approval process involved evaluation of more than 500 PBC participants across multiple studies, including the long-term ASSURE study. The most commonly reported adverse events were manageable: headache (8%), abdominal pain (7%), nausea (6%), abdominal distension (6%), and dizziness (5%). Notably, no treatment-related serious adverse events were identified during the trial.

However, important safety considerations exist. Fracture risk increased to 4% in seladelpar-treated patients versus 0% in placebo groups, warranting monitoring of bone health. Additionally, dose-dependent liver enzyme elevations were observed at higher doses, necessitating baseline and periodic liver function monitoring.

The Path Forward

The FDA granted accelerated approval based on ALP reduction, but importantly, improvement in survival or prevention of liver decompensation events have not yet been demonstrated. Continued approval may depend on results from the confirmatory Phase 3 AFFIRM study, which is actively enrolling patients with compensated cirrhosis due to PBC.

Seladelpar has also been submitted for review by the UK Medicines and Healthcare products Regulatory Agency (MHRA) and the European Medicines Agency (EMA), suggesting potential global expansion of this treatment option.

Practical Application

Seladelpar is administered as an oral once-daily 10 mg tablet. It can be used either in combination with UDCA for inadequate responders or as monotherapy in UDCA-intolerant patients. The drug is contraindicated in patients with decompensated cirrhosis (characterized by ascites, variceal bleeding, or hepatic encephalopathy).

Several drug interactions require clinical attention: strong CYP2C9 inhibitors and OAT3 inhibitors should be avoided due to increased seladelpar exposure. Additionally, bile acid sequestrants must be separated from seladelpar administration by at least four hours.

Implications for the Medical Community

This approval represents a paradigm shift in how physicians approach PBC management. With seladelpar now available, providers can shift treatment goals beyond symptom management to include ALP normalization—a recognized surrogate marker of disease progression. For patients experiencing inadequate response to conventional therapy, this medication offers a pharmacologically distinct option backed by robust clinical evidence.

The confirmation studies currently underway will ultimately determine whether this biochemical benefit translates into clinically meaningful outcomes such as reduced transplant rates and improved survival—the true measure of therapeutic value in chronic liver disease.