▎WuXiangEdited by Kant Content Team

Gilead Sciences announced today that the U.S.FDALivdelzi (seladelpar) has been granted accelerated approval in combination with ursodeoxycholic acid (UDCA) for the treatment of primary biliary tract infections that have an inadequate response to UDCA.CirrhosisLivdelzi is not recommended for use in adults with precompensated cirrhosis (PBC) or as monotherapy in patients who are intolerant to UDCA, but is not recommended in patients who have or develop decompensated cirrhosis.According to the press release, Livdelzi wasNormalization of alkaline phosphatase (ALP)、Key biomarkers andItchingThe first treatment to demonstrate a statistically significant improvement compared to placebo in control.Livdelzi's marketing application is currently being evaluated by the UK Medicines and Healthcare products Regulatory Agency (MHRA) and the European Medicines Agency (EMA).

Primary biliary cholangitis is a potentially life-threatening liver diseaseAutoimmune diseases。As the immune system continues to attack the bile ducts, bile flow is obstructed and accumulates, and toxic bile acids are retained in the liver, which can develop into liver fibrosis, cirrhosis and liver failure.Other clinical symptoms include fatigue and pruritus.One in 1,000 women over 40 years of age develops PBC.

The accelerated approval was based on data from the pivotal placebo-controlled Phase 3 RESPONSE study.At month 12, 62% of participants who received once-daily oral Livdelzi achieved the primary endpoint of composite biochemical response, compared with only 20% of those who received placebo.After treatment with Livdelzi, 25% of patients achieved normalization of ALP values ​​at month 12, while none of the patients in the placebo group experienced such a change.ALP is a cholestatic marker that predicts the risk of liver transplantation and death.

The change from baseline in pruritus scores at month 6 was a key secondary endpoint of the trial. Patients taking Livdelzi experienced a significant reduction in pruritus compared to those taking placebo.Livdelzi is the first drug to demonstrate significant and durable improvements in pruritus and cholestatic markers, which are associated with the risk of disease progression, in a Phase 3 trial.

Image source: 123RF

The most common adverse events (≥5%)Patients in the Livdelzi groupheadache, abdominal pain, nausea, bloating, and dizziness,No treatment-related serious adverse events (SAEs) were observed.

To date, Livdelzi has been examined in more than 500 patients with PBC in RESPONSE and other trials, including the long-term open-label ASSURE study and previous earlier studies. 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 patients with compensated cirrhosis due to PBC.

▲Seladelpar molecular formula (Image source: PubChem)

LivdelziIt is an oral, potent, selective peroxisome proliferator-activated receptor δ (PPAR δ) agonist.PPARδ is expressed in multiple cell types in the liver, and preclinical data show that it regulates multiple genes that regulate bile acid synthesis, inflammation, and fibrosis. The drug was granted breakthrough therapy designation by the U.S. FDA in February 2019 for the treatment of PBC. The therapy was originally developed by CymaBay, and Gilead Sciences reached a total of $4.3 billion with the company in February 2024., and thus obtain this treatment.

June this yearUS FDAIpsen's Iqirvo (elafibranor) 80 mg tablets are indicated for the treatment of adult PBC patients who have an inadequate response to UDCA in combination with UDCA, or as monotherapy for patients who are intolerant of UDCA. Iqirvo is a once-daily, oral, "first-in-class" PPAR α/δ agonist.Simultaneous targeting of PPARα/δ activation could potentially treat inflammation, cholestasis, and fibrosis in PBC.According to the press release, Iqirvo is the first drug approved in nearly a decade to treat the rare liver disease primary biliary tract infection.cholangitisnew drug.

Apart fromLivdelzi and IqirvoCurrently, therapies being developed for the treatment of PBC include the Phase 3 trial developed by GSK.Ileal bile acid transporter (IBAT)Oral small moleculesInhibitor linerixibat, whose Phase 3 trial has recruited 238 patients, is expected to have preliminary results in October this year.NOX1/4 inhibitor setanaxibThe Phase II clinical trial was also completed recently, and the full trial results are expected to be announced in the second half of this year. The therapy has been granted orphan drug status by the EMA and the US FDA, and has been granted fast track status by the FDA for the treatment of PBC.Mirum Pharmaceuticals is also developing selectiveASBT small molecule inhibitor volixibatFor the treatment of PBC, the Phase 2 trial of this therapy is currently recruiting patients and preliminary results are expected in December next year.Cascade PharmaceuticalsFXR-targeted agonist linafexorThe Phase 2 trial of (CS0159) is also recruiting patients, and preliminary results are expected to be announced in October this year.

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