Seladelpar

Gilead Science’s Livdelzi (seladelpar) has been granted accelerated approval by the US Food and Drug Administration (FDA) to treat primary biliary cholangitis (PBC). The PPAR delta agonist has been authorised for use alongside ursodeoxycholic acid (UDCA) to treat adults who have an inadequate response to UDCA, and also as monotherapy for patients who are unable to tolerate UDCA. Affecting approximately 130,000 people in the US, PBC is a rare autoimmune disease of the bile ducts that mainly affects women. Pruritus, or itching, and fatigue are among the most common early symptoms of PBC, and the disease can cause liver damage and possible liver failure if left untreated. The FDA’s decision was supported by positive results from the late-stage RESPONSE study, in which 62% of patients receiving oral Livdelzi achieved the primary endpoint of composite biochemical response after 12 months, versus 20% of those on placebo. Treatment with Livdelzi led to normalisation of alkaline phosphatase (ALP) values, a cholestatic marker that is a predictor of risk for liver transplant and death, in 25% of patients at 12 months, while this change was not seen in any patients receiving placebo. Livdelzi-treated patients also demonstrated a statistically significant reduction in pruritus compared with placebo. In line with the FDA’s accelerated approvals pathway, continued approval of Livdelzi in this indication may be contingent on the verification of clinical benefit in a confirmatory trial. Daniel O’Day, chairman and chief executive officer at Gilead, said: “People living with PBC have been waiting for treatment advancements for many years. [This] approval of Livdelzi, with its distinct profile, provides them with an important new option.” Gilead gained access to Livdelzi in March through its $4.3bn acquisition of CymaBay Therapeutics. The company recently shared positive data from the open-label ASSURE study, which has been evaluating the long-term safety and efficacy of Livdelzi in adults with PBC who had previously participated in a trial of the drug and who had not responded adequately to UDCA. Results showed that 70% of 148 patients receiving an oral 10mg dose of Livdelzi once daily achieved the clinically meaningful composite response endpoint and 37% achieved ALP normalisation after 12 months.

This approval is particularly significant for patients who have had an inadequate response to ursodeoxycholic acid (UDCA), the current standard of care, or for those who are unable to tolerate UDCA. With no cure currently available for PBC, the introduction of Livdelzi provides a critical new treatment option for this underserved patient population. Livdelzi’s approval was driven by compelling results from the pivotal Phase 3 RESPONSE study, which demonstrated its efficacy and safety in treating PBC. In this double-blind, placebo-controlled study, 62% of patients who were treated with Livdelzi achieved the primary endpoint of a composite biochemical response at 12 months, compared to just 20% of those in the placebo group. Moreover, Livdelzi was shown to normalize alkaline phosphatase (ALP) levels—a key biomarker associated with the risk of liver transplant and mortality—in 25% of the patients. This normalization was not observed in any of the placebo group participants. Additionally, patients treated with Livdelzi experienced a statistically significant reduction in pruritus, a debilitating symptom characterized by chronic itching that severely impacts the quality of life for people with PBC. Carol Roberts, president of The PBCers Organization,  the imporbelieveis in the importance of this new treatment option: She told OSP: “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.” googletag.cmd.push(function () { googletag.display('text-ad1'); }); The approval of Livdelzi offers hope to the estimated 130,000 Americans, predominantly women, who live with this progressive liver disease. Primary biliary cholangitis, if left untreated, can lead to severe liver damage and potentially liver failure. Current treatment options, such as UDCA, are not effective for all patients, leaving a significant unmet need. Livdelzi, an oral peroxisome proliferator-activated receptor (PPAR) delta agonist, represents a new approach in managing the disease. It works by regulating genes involved in bile acid synthesis, inflammation, lipid metabolism, and fibrosis, ultimately aiming t. He said: reduce disease progression by normalizing ALP levels, a recognized surrogate marker for PBC progression. Daniel O’Day, chairman and chief executive officer of Gilead Sciences, highlighted the impact of Livdelzi’s approval, stating, “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. 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.” Gilead’s commitment to patients extends beyond the approval of Livdelzi. The company has initiated the AFFIRM study, a Phase 3 randomized, placebo-controlled confirmatory trial, to further evaluate the long-term clinical outcomes of Livdelzi in patients with compensated cirrhosis due to PBC. The ongoing ASSURE study, a long-term open-label trial, and data from earlier phase studies, contribute to a robust understanding of Livdelzi’s sustained efficacy and safety profile. Gilead also offers the Support Path Program, which provides resources to help patients navigate coverage and financial options for Livdelzi. Following Gilead's acquisition of CymaBay, the company has pledged to continue funding PBC patient organizations, demonstrating its long-term commitment to the PBC community. Livdelzi has already garnered FDA Breakthrough Therapy and Orphan Drug Designations, with regulatory reviews also in progress in the UK and EU. As part of the FDA’s accelerated approval, continued marketing of Livdelzi will depend on the confirmation of clinical benefits in ongoing studies, particularly in reducing ALP levels, a critical marker in managing PBC. With Livdelzi’s approval, Gilead is poised to significantly impact the treatment landscape for PBC, offering a new lifeline to patients with few other options.