Livdelzi approved in UK as PBC treatment for certain adults
Oral therapy to be used in combination with UDCA, or as standalone drug
Gilead Sciences’ Livdelzi (seladelpar) has been approved in the U.K. as a treatment for adults with primary biliary cholangitis (PBC), either in combination with ursodeoxycholic acid (UDCA) for people who failed to respond adequately to UDCA, or as a standalone therapy for those who cannot tolerate UDCA.
With this approval by the U.K.’s Medicines and Healthcare products Regulatory Agency (MHRA), the once-daily oral therapy will soon become available to the estimated 25,000 people in Great Britain who live with the rare liver disease. As with any medicine, the MHRA will continue to monitor how safe and effective Livdelzi is in these patients, the agency noted in a press release announcing the decision.
“Keeping patients safe and enabling their access to high quality, safe and effective medical products are key priorities for us,”said Julian Beach, MHRA’s interim executive director of healthcare quality and access. “We’re assured that the appropriate regulatory standards for the approval of this medicine have been met. As with all products, we will keep its safety under close review.”
Livdelzi was approved in the U.S. last year for the same indication, but under an accelerated approval program that allows promising experimental therapies to be approved based on preliminary data while the company runs additional studies to confirm its effectiveness.
The medication is also under review in the European Union, where an advisory committee has already recommended that Livdelzi be approved in combination with UDCA for people who failed to respond to first-line UDCA therapy, or on its own for those who cannot tolerate UDCA. A final decision from the European Commission is expected soon.
New UK PBC treatment approved in US, under review in EU
PBC is an autoimmune disease marked by cholangitis, which refers to inflammation in the bile ducts that carry the digestive fluid bile from the liver to the intestines. When inflammation damages the bile ducts, the flow of bile may be disrupted, causing it to accumulate in the liver and leak into the bloodstream. This can result in itchy skin, known medically as pruritis, and a range of other symptoms.
UDCA, sold in the U.S. as Actigall and Urso, is the standard first-line treatment for PBC, helping to speed the flow of bile from the liver. But it doesn’t work well for everyone, and some patients cannot tolerate its side effects, leading them to stop taking the medication.
Livdelzi belongs to a group of medications called peroxisome proliferator-activated receptor (PPAR) agonists. As their name suggests, these therapies work by activating the PPAR-delta protein, which reduces the production of bile acid, a component of bile, in the liver. This is expected to prevent damage to the liver and reduce the levels of bile in circulation, easing itching.
The drug’s approval in the U.K. mainly drew on positive data from RESPONSE (NCT04620733), a Gilead-sponsored Phase 3 clinical study that tested daily treatment with Livdelzi against a placebo over one year. That trial involved 193 adults with PBC whose symptoms were not well controlled with UDCA or who had experienced unacceptable side effects with that therapy.
Livdelzi helped a greater percentage of patients achieve a biochemical response, defined as specific reductions in two markers of liver damage — alkaline phosphatase and total bilirubin — compared with a placebo. Alkaline phosphatase reached normal levels after one year in 25% of patients on Livdelzi, but in none of those on the placebo.
Daily treatment with Livdelzi also significantly reduced itching compared with the placebo, and slightly more than a quarter of patients (26.5%) with moderate itching at the trial start had near-complete relief after a year on the PBC treatment. Among those with more severe itching at the study’s start, 18.8% had near-complete resolution of itching.
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