With an FDA approval in hand for primary biliary cholangitis (PBC) treatment Livdelzi (seladelpar), Gilead Sciences enters arenas that are both new and old.
While the California drugmaker is launching an inflammatory drug for the first time, it also is familiar territory for the company as PBC is a liver disorder—which means that most of the physicians who prescribe medicines from Gilead’s blockbuster hepatitis portfolio are the same ones treating PBC patients.
“Seladelpar fits right in our sweet spot, in our wheelhouse,” Johanna Mercier, Gilead’s chief commercial officer, said in an interview. “It’s a great strategic fit with liver diseases, which is something we are incredibly well established in—hep C, hep D, hep B. In addition to that, it also fits in those three therapeutic areas that we’re focused on—virology, oncology, inflammation.”
Those are the priority areas for Gilead as it tries to transform into a more diversified company. Last year, 68% of its $26.9 billion in revenue was generated by its HIV products.
“We have a team on the ground—both medical and commercial—that currently visits hepatologists. About 80% of those prescribers are actually prescribers of PBC,” Mercier said. “That’s why it’s such a perfect fit, because we’re gonna leverage that commercial footprint and that expertise and that network of contacts to make sure we can get to these people quickly to share with them the news of seladelpar and the value that it brings.”
The company’s initial move into inflammation could help balance the portfolio. One of the most bullish projections for Livdelzi, from Cantor Fitzgerald, pegs its peak annual sales at $2 billion.
The FDA approved Livdelzi as a second-line treatment for adults with PBC. First-line therapy is generic ursodeoxycholic acid (UDCA). For those who are not responsive to UDCAs, Livdelzi can be added to their regimen. For others who can’t tolerate UDCAs, Livdelzi can be taken as a monotherapy.
The FDA granted its nod on an accelerated basis. Gilead will need to show Livdelzi’s value in a long-term confirmatory trial to earn a full approval. As PBC reduces life expectancy, showing a survival benefit would go a long way toward clinching the full endorsement.
Gilead acquired Livdelzi in its $4.3 billion buyout of CymaBay Therapeutics six months ago. It was a 27% premium on the share price of the California biotech after it presented results from a phase 3 study that indicated Livdelzi was not only primed for approval but also had potential to be the top product on the market to treat the condition.
The phase 3 RESPONSE study hit its primary endpoint as 62% of patients on Livdelzi achieved composite biochemical response at 12 months, versus 20% on placebo. At that time, the unusually high response rate for a dummy drug raised some eyebrows about the design of the trial.
Some of those concerns were alleviated as treatment with Livdelzi also led to a normalization of alkaline phosphatase values—a cholestatic biomarker that is a predictor of risk for liver transplant and death—in 25% of patients, versus 0% on placebo after 12 months.
The most common adverse events were headache, abdominal pain, nausea, abdominal swelling and dizziness. There were no treatment-related serious adverse events, as determined by the study investigators.
Though it wasn’t the primary endpoint, the trial’s most impactful result—and the one that will likely resound most favorably with patients—surrounded Livdelzi’s ability to reduce the persistent itch, or pruritus, that often accompanies PBC.
“We believe that the differentiation that seladelpar brings for patients is second to none,” Mercier said. “To have a drug that can not only manage and reduce your liver enzymes but also reduce the pruritus is incredibly differentiating for patients.”
The list price for a 10-mg dose of Livdelzi is $12,606 for 30 days, which works out to $151,272 per year.
Livdelzi will compete with Intercept Pharmaceuticals’ Ocaliva, which was approved for the disorder in 2016. Ocaliva remains the only second-line therapy for the disorder showing significant improvement for liver transplant-free and liver decompensation-free survival.
Before Intercept was acquired by Italian private company Alfasigma last year for $800 million, it expected sales of Ocaliva in 2023 to total between $320 million and $340 million.
Additionally, two months ago, French companies Genfit and Ipsen scored approval for their PBC drug Iqirvo, which comes from the same general drug class as Livdelzi as it is a peroxisome proliferator-activated receptor (PPAR) agonist.
While Iqirvo scored the first-in-class FDA nod, Livdelzi's trial data suggests it is more effective in reducing pruritis. There also is a slight difference in how they work as Iqirvo acts on PPAR alpha and delta, while Livdelzi acts solely on PPAR delta.
PBC is a rare, chronic, autoimmune disease of the bile ducts that affects approximately 130,000 in the US, primarily women, and can cause liver damage and possible liver failure if untreated.
“Those living with PBC share common symptoms, including incessant itching or skin-crawling sensations, as well as debilitating fatigue that is made worse by the itching at night,” Carol Roberts, president of a patient advocacy group called the PBCers Organization, said in Gilead’s release Wednesday. “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.”