Gilead gains accelerated FDA approval for rare liver disease treatment

US big pharma Gilead Sciences has won an accelerated US FDA approval for peroxisome proliferator-activated receptor delta agonist seladelpar (Livdelzi) for treatment of primary biliary cholangitis in combination with ursodeoxycholic acid.

The accelerated approval comes after the phase 3 RESPONSE study showed​ 62% of patients treated with seladelpar achieved a composite biochemical response at 12 months versus 20% of those taking placebo. The main part of this response was a reduction in alkaline phosphatase, which can be a predictor for liver transplant at high levels.

The drug approval is as a combination therapy for adults with the autoimmune condition who do not respond adequately to ursodeoxycholic acid, one of the only treatments for the condition, or alone in those who are unable to tolerate the older therapy.

It is the first time Gilead is entering the inflammatory drug space, but the company has a lot of experience developing drugs for other liver disorders such as hepatitis.

The big pharma acquired seladelpar earlier this year when it acquired​ California-based biotech CymaBay for US $4.3 billion. At the point of acquisition, seladelpar was already being evaluated for approval by the FDA.

Meeting an unmet need​

Primary biliary cholangitis impacts around one in 3,000-4,000 people and is much more common in women and those over the age of 40 years.

It is an autoimmune condition and results in gradual destruction of the small bile ducts in the liver, which can cause bile and other toxic substances to build up in the liver. In its later stages it can lead to fibrosis and eventually cirrhosis of the liver.

There is an unmet need for new treatments for this condition as for many years the secondary bile acid, ursodeoxycholic acid, was the only option for patients. More recently, a semi-synthetic bile acid analog obeticholic acid was also approved.

Ursodeoxycholic acid improves liver enzyme levels, slows progression and improves liver transplant free survival, but there has been some debate about how effective it is with some studies suggesting it does not​ have a benefit on mortality or liver transplantation rates, itching or fatigue in patients with primary biliary cirrhosis.

Focusing in on rare disease​

Seladelpar was originally developed by big pharma Johnson & Johnson, who then licensed the drug to CymaBay to develop further in 2006.

It was originally designed to treat metabolic dysfunction-associated steatohepatitis (MASH) but trials were put on hold in 2019 by the FDA during testing for this indication due to some concerns about safety.

After the regulator allowed trials to continue the following year the company decided to change the indication and focus on treating primary biliary cholangitis, which was ultimately successful.

“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,” said Daniel O’Day, Chairman and CEO, Gilead Sciences. “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.”