FDA Grants Accelerated Approval to Gilead’s PBC Drug

Rare Daily Staff

The U.S. Food and Drug Administration granted accelerated approval to Gilead Sciences’ Livdelzi for the treatment of the rare liver disease primary biliary cholangitis.

The approval is for use of Livdelzi 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. Livdelzi is not recommended for people who have or develop decompensated cirrhosis.

Gilead acquired Livdelzi through its $4.3 billion acquisition of CymaBay earlier this year. It adds to Gilead’s existing strength in liver disease

Primary biliary cholangitis (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.

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

The accelerated approval was based primarily on data from the pivotal placebo-controlled Phase 3 RESPONSE study. In the study, 62 percent of participants taking Livdelzi achieved the primary endpoint of composite biochemical response at month 12, versus 20 percent of participants taking placebo.

Treatment with Livdelzi led to normalization of alkaline phosphatase (ALP) values in 25 percent of trial participants at month 12. ALP is a cholestatic marker that is a predictor of risk for liver transplant and death. This change was not seen in any trial participants receiving placebo.

Change from baseline pruritus score at month six was a key secondary endpoint; patients treated with Livdelzi demonstrated a statistically significant reduction in pruritus compared with placebo.

As part of the FDA accelerated approval, Gilead has committed to a confirmatory long-term outcomes study called AFFIRM, which has already been initiated in people with compensated cirrhosis. Continued approval may be contingent upon verification of clinical benefit in confirmatory studies.

“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 of 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.”

Photo: Carol Roberts, president of The PBCers Organization