Gilead Sciences, Inc.  announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval for Livdelzi^® (seladelpar) for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults who have had an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA. The use of Livdelzi is not recommended for people who have or develop decompensated cirrhosis.

The accelerated approval was based primarily on data from the pivotal placebo-controlled Phase 3 RESPONSE study. In the study, 62% of participants taking Livdelzi achieved the primary endpoint of composite biochemical response at month 12, versus 20% of participants taking placebo. Treatment with Livdelzi led to normalization of alkaline phosphatase (ALP) values, a cholestatic marker that is a predictor of risk for liver transplant and death, in 25% of trial participants at month 12. This change was not seen in any trial participants receiving placebo. Change from baseline pruritus score at month 6 was a key secondary endpoint; patients treated with Livdelzi demonstrated a statistically significant reduction in pruritus compared with placebo.

The FDA approved Livdelzi under accelerated approval based on a reduction of ALP. Improvement in survival or prevention of liver decompensation events have not been demonstrated. Continued approval of Livdelzi for the approved indication may be contingent on verification and description of clinical benefit in confirmatory trial(s).

“More people are being diagnosed with PBC, impacting people of varied ages, gender, race and ethnicity. 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,” said Carol Roberts, President, The PBCers Organization. “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.”

PBC is a rare, chronic, autoimmune disease of the bile ducts that affects approximately 130,000 Americans, primarily women, and can cause liver damage and possible liver failure if untreated. The disease currently has no cure.

Livdelzi, an oral, peroxisome proliferator activated receptor (PPAR) delta agonist, or delpar, is positioned to challenge the current PBC standard of care, which falls short for many people who experience inadequate response to treatment, putting them at risk for continued liver damage. Livdelzi has demonstrated a sustained efficacy and safety profile across its robust development program to date, including a capacity to normalize ALP levels for some of the people studied with PBC. Given ALP levels are recognized as an important surrogate marker of disease progression in PBC, providers are shifting to view ALP normalization as a treatment goal.

“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,” said Daniel O’Day, Chairman and Chief Executive Officer, Gilead Sciences. “We look forward to leveraging Gilead’s long-standing expertise in liver disease to bring this promising new treatment to all those who could benefit.”

The RESPONSE study, in addition to other studies including the long-term open-label ASSURE study and prior earlier phase studies, together represent the experience with Livdelzi in more than 500 participants with PBC. Ongoing studies include the confirmatory Phase 3 AFFIRM study, a randomized, placebo-controlled confirmatory study designed to evaluate the effect of Livdelzi on clinical outcomes in people with compensated cirrhosis due to PBC.

In the RESPONSE study, Livdelzi, given alone or in combination with UDCA as an oral, once-daily medicine, reduced key biomarkers of PBC disease and helped reduce pruritus (chronic itch), which is a common symptom that can significantly impair quality of life in people with PBC. Livdelzi is the only medicine to demonstrate statistically significant and durable improvements in both pruritus and markers of cholestasis related to the risk of disease progression in a Phase 3 trial. The primary endpoint of the study was a composite biochemical response at month 12, where biochemical response was defined as achieving ALP less than 1.67-times upper limit of normal (ULN), an ALP decrease of greater than or equal to 15% from baseline, and total bilirubin less than or equal to ULN. ALP normalization (i.e., ALP less than or equal to ULN) at month 12 and change from baseline in pruritus score at month 6 were key secondary endpoints. The most common adverse events (reported in ≥5% of trial participants in the Livdelzi arm and higher compared to placebo) were headache, abdominal pain, nausea, abdominal distension (swelling) and dizziness. There were no treatment-related serious adverse events (SAEs), as determined by the study investigators.

Commitment to Advocacy, Access and Global Reach

The Gilead Support Path^® Program offers information and resources to help patients who are prescribed Livdelzi understand coverage and financial options.

Following the acquisition of CymaBay, Gilead will continue to provide funding to PBC patient organizations.

Livdelzi received FDA Breakthrough Therapy Designation, as well as Orphan Drug Designation for the treatment of people living with PBC.

Seladelpar has also been accepted for review by the UK Medicines and Healthcare products Regulatory Agency (MHRA) and the European Medicines Agency (EMA).