The FDA has set a Prescription Drug User Fee Act target action date of Aug. 14, 2024, for seladelpar to treat adults with primary biliary cholangitis.
The FDA has granted priority review for CymaBay’s seladelpar to treat adults with primary biliary cholangitis (PBC), including those with itch in patients without cirrhosis or those who are intolerant to ursodeoxycholic acid. The agency has set a Prescription Drug User Fee Act (PDUFA) target action date of Aug. 14, 2024
PBC is a progressive autoimmune disease that results from the destruction of the bile ducts in the liver. This leads to inflammation, scarring and cirrhosis. The disease affects mostly women.
Seladelpar is an orally active PPARδ agonist that has demonstrated a statistically significant improvement in biochemical markers of disease progression. The NDA includes data from more than 500 people living with PBC, including from the placebo-controlled phase 3 RESPONSE and ENHANCE studies, the long-term open-label ASSURE study, and prior phase 2 studies.
The FDA had updated the Breakthrough Therapy Designation for seladelpar in October 2023 in recognition of clinical data that indicated seladelpar may provide meaningful improvement over existing therapy based on a reduction in alkaline phosphatase (ALP) and improvement in pruritus (itching) in patients without cirrhosis or with compensated cirrhosis.
In In the pivotal RESPONSE trial, seladelpar achieved statistical significance over placebo across primary composite endpoints of biochemical response (61.7% for patients on seladelpar vs 20.0% for placebo), normalization of alkaline phosphatase at 12 months (25.0% for patients on seladelpar vs 0.0% for placebo) and statistically significant improvement in pruritus at six months among people living with moderate-to-severe itch that was sustained through 12 months.
Attaining alkaline phosphatase ≤1x upper limit of normal (ULN) or bilirubin levels ≤0.6 × ULN in observational studies was associated with the lowest risk for liver transplant or death in patients with PBC.
In January 2024, results from the ENHANCE study were published in Hepatology about the impact of seladelpar on itch in patients with PBC. In this post-hoc analysis, seladelpar reduced serum interleukin-31 (IL-31) levels, bile acids, and pruritis. In this study, IL-31 serum levels were measured in people with PBC who received daily oral doses of seladelpar 5 mg or 10 mg compared with placebo for three months. Statistically significant dose-dependent decreases in IL-31 were observed with both doses of seladelpar 5 mg.
Separately, Gilead Sciences has announced that it will acquire CymaBay for about $4.3 billion. The transaction is expected to close during the first quarter of 2024,
The FDA is also reviewing another therapy for second-line treatment of PBC. Ipsen’s elafibranor has a Prescription Drug User Fee Act action date of June 10, 2024.