RARE Daily

FDA Revises Breakthrough Therapy Designation for CymaBay’s Treatment for Primary Biliary Cholangitis

October 23, 2023

Rare Daily Staff

The U.S. Food and Drug Administration has revised the originally granted Breakthrough Therapy Designation for CymaBay Therapeutics’ seladelpar to now reflect treatment of primary biliary cholangitis including pruritus in adults without cirrhosis or with compensated cirrhosis.

Seladelpar is the only potent, selective, orally active PPARδ agonist, or delpar, with phase 3 results demonstrating a statistically significant improvement in primary biliary cholangitis (PBC)-related cholestatic pruritus.

PBC is a rare, chronic inflammatory liver disease primarily affecting women (1 in 1,000 women over the age of 40 or about 130,000 total people in the U.S.). PBC is characterized by impaired bile flow (known as cholestasis) and the accumulation of toxic bile acids in the liver, leading to inflammation and destruction of the bile ducts within the liver and causing increased levels of ALP and total bilirubin. The most common early symptoms of PBC are pruritus (itching) and fatigue, which can be debilitating for some patients. Progression of PBC is associated with an increased risk of liver-related mortality.

Breakthrough Therapy Designation is granted by the FDA to investigational agents intended to treat a serious or life-threatening disease or condition and whose preliminary clinical evidence may demonstrate substantial improvement on at least one clinically significant endpoint over available therapy. This program was designed by the FDA to help ensure patients gain access to important new therapies through FDA approval as soon as possible.

The FDA’s original Breakthrough Therapy designation for seladelpar was granted in 2019 and was based on preliminary results from a phase 2 clinical trial, which showed that seladelpar was associated with a substantial reduction in serum alkaline phosphatase (ALP). The updated Breakthrough Therapy designation of seladelpar was granted based on additional evidence provided to the Agency, which supports that seladelpar may provide substantial improvement over existing therapy based on a reduction in ALP and pruritus in patients without cirrhosis or with compensated cirrhosis.

“The decision by the FDA to grant Breakthrough Therapy designation emphasizes the significant impact of pruritus on day-to-day functioning for people living with PBC and underscores the potential of seladelpar to help fill a critical need for a treatment that both significantly reduces markers of cholestasis and pruritus in patients with PBC, including those with compensated cirrhosis,” said Klara Dickinson, chief regulatory and compliance officer of CymaBay Therapeutics. “A Breakthrough Therapy designation is accompanied by the benefit to submit the NDA on a rolling basis. We look forward to working closely with the FDA during the review process and remain focused on bringing seladelpar to patients with PBC as quickly as possible.”

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