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The US Food and Drug Administration (FDA) granted accelerated approval for Livdelzi (seladelpar, Gilead Sciences, Inc.) for primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults who fail to respond adequately to UDCA, or as monotherapy in those who can’t tolerate UDCA. 

Livdelzi, a selective agonist of peroxisome proliferator–activated receptor delta, is not recommended in adults who have or develop decompensated cirrhosis.

PBC is a rare, chronic, autoimmune disease of the bile ducts that affects roughly 130,000 Americans, primarily women, and can cause liver damage and possible liver failure if untreated. The disease currently has no cure.

The FDA approved Livdelzi based largely on results of the phase 3 RESPONSE study, in which the drug significantly improved liver biomarkers of disease activity and bothersome symptoms of pruritus in adults with PBC.

The primary endpoint of the trial was a biochemical response, defined as an alkaline phosphatase (ALP) level < 1.67 times the upper limit of the normal range, with a decrease of 15% or more from baseline, and a normal total bilirubin level, at 12 months.

After 12 months, 62% of patients taking Livdelzi met the primary endpoint vs 20% of patients taking placebo.

In addition, significantly more patients taking Livdelzi than placebo had normalization of the ALP level (25% vs 0%). The average decrease in ALP from baseline was 42.4% in the Livdelzi group vs 4.3% in the placebo group.

At 12 months, alanine aminotransferase and gamma-glutamyl transferase levels were reduced by 23.5% and 39.1%, respectively, in the Livdelzi group compared with 6.5% and 11.4%, respectively, in the placebo group.

A key secondary endpoint was change in patient-reported pruritus.

At baseline, 38.3% of patients in the Livdelzi group and 35.4% of those in the placebo group had moderate to severe pruritus, with a daily numerical rating scale (NRS) score ≥ 4 out of 10.

Among these patients, the reduction from baseline in the pruritus NRS score at month 6 was significantly greater with Livdelzi than with placebo (change from baseline, -3.2 vs -1.7 points). These improvements were sustained through 12 months.

Improvements on the 5-D Itch Scale in both the moderate- to severe-pruritis population and the overall population also favored Livdelzi over placebo for itch relief, which had a positive impact on sleep.

“The availability of a new treatment option that can help reduce [the] intense itching while also improving biomarkers of active liver disease is a milestone for our community,” Carol Roberts, president, The PBCers Organization, said in a news release announcing the approval. 

The most common adverse reactions with Livdelzi were headache, abdominal pain, nausea, abdominal distension, and dizziness.

The company noted that the FDA granted accelerated approval for Livdelzi based on a reduction of ALP. Improvement in survival or prevention of liver decompensation events have not been demonstrated. Continued approval of Livdelzi for PBC may be contingent on verification and description of clinical benefit in confirmatory trial(s).
 

A version of this article appeared on Medscape.com.

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The US Food and Drug Administration (FDA) granted accelerated approval for Livdelzi (seladelpar, Gilead Sciences, Inc.) for primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults who fail to respond adequately to UDCA, or as monotherapy in those who can’t tolerate UDCA. 

Livdelzi, a selective agonist of peroxisome proliferator–activated receptor delta, is not recommended in adults who have or develop decompensated cirrhosis.

PBC is a rare, chronic, autoimmune disease of the bile ducts that affects roughly 130,000 Americans, primarily women, and can cause liver damage and possible liver failure if untreated. The disease currently has no cure.

The FDA approved Livdelzi based largely on results of the phase 3 RESPONSE study, in which the drug significantly improved liver biomarkers of disease activity and bothersome symptoms of pruritus in adults with PBC.

The primary endpoint of the trial was a biochemical response, defined as an alkaline phosphatase (ALP) level < 1.67 times the upper limit of the normal range, with a decrease of 15% or more from baseline, and a normal total bilirubin level, at 12 months.

After 12 months, 62% of patients taking Livdelzi met the primary endpoint vs 20% of patients taking placebo.

In addition, significantly more patients taking Livdelzi than placebo had normalization of the ALP level (25% vs 0%). The average decrease in ALP from baseline was 42.4% in the Livdelzi group vs 4.3% in the placebo group.

At 12 months, alanine aminotransferase and gamma-glutamyl transferase levels were reduced by 23.5% and 39.1%, respectively, in the Livdelzi group compared with 6.5% and 11.4%, respectively, in the placebo group.

A key secondary endpoint was change in patient-reported pruritus.

At baseline, 38.3% of patients in the Livdelzi group and 35.4% of those in the placebo group had moderate to severe pruritus, with a daily numerical rating scale (NRS) score ≥ 4 out of 10.

Among these patients, the reduction from baseline in the pruritus NRS score at month 6 was significantly greater with Livdelzi than with placebo (change from baseline, -3.2 vs -1.7 points). These improvements were sustained through 12 months.

Improvements on the 5-D Itch Scale in both the moderate- to severe-pruritis population and the overall population also favored Livdelzi over placebo for itch relief, which had a positive impact on sleep.

“The availability of a new treatment option that can help reduce [the] intense itching while also improving biomarkers of active liver disease is a milestone for our community,” Carol Roberts, president, The PBCers Organization, said in a news release announcing the approval. 

The most common adverse reactions with Livdelzi were headache, abdominal pain, nausea, abdominal distension, and dizziness.

The company noted that the FDA granted accelerated approval for Livdelzi based on a reduction of ALP. Improvement in survival or prevention of liver decompensation events have not been demonstrated. Continued approval of Livdelzi for PBC may be contingent on verification and description of clinical benefit in confirmatory trial(s).
 

A version of this article appeared on Medscape.com.

 

The US Food and Drug Administration (FDA) granted accelerated approval for Livdelzi (seladelpar, Gilead Sciences, Inc.) for primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults who fail to respond adequately to UDCA, or as monotherapy in those who can’t tolerate UDCA. 

Livdelzi, a selective agonist of peroxisome proliferator–activated receptor delta, is not recommended in adults who have or develop decompensated cirrhosis.

PBC is a rare, chronic, autoimmune disease of the bile ducts that affects roughly 130,000 Americans, primarily women, and can cause liver damage and possible liver failure if untreated. The disease currently has no cure.

The FDA approved Livdelzi based largely on results of the phase 3 RESPONSE study, in which the drug significantly improved liver biomarkers of disease activity and bothersome symptoms of pruritus in adults with PBC.

The primary endpoint of the trial was a biochemical response, defined as an alkaline phosphatase (ALP) level < 1.67 times the upper limit of the normal range, with a decrease of 15% or more from baseline, and a normal total bilirubin level, at 12 months.

After 12 months, 62% of patients taking Livdelzi met the primary endpoint vs 20% of patients taking placebo.

In addition, significantly more patients taking Livdelzi than placebo had normalization of the ALP level (25% vs 0%). The average decrease in ALP from baseline was 42.4% in the Livdelzi group vs 4.3% in the placebo group.

At 12 months, alanine aminotransferase and gamma-glutamyl transferase levels were reduced by 23.5% and 39.1%, respectively, in the Livdelzi group compared with 6.5% and 11.4%, respectively, in the placebo group.

A key secondary endpoint was change in patient-reported pruritus.

At baseline, 38.3% of patients in the Livdelzi group and 35.4% of those in the placebo group had moderate to severe pruritus, with a daily numerical rating scale (NRS) score ≥ 4 out of 10.

Among these patients, the reduction from baseline in the pruritus NRS score at month 6 was significantly greater with Livdelzi than with placebo (change from baseline, -3.2 vs -1.7 points). These improvements were sustained through 12 months.

Improvements on the 5-D Itch Scale in both the moderate- to severe-pruritis population and the overall population also favored Livdelzi over placebo for itch relief, which had a positive impact on sleep.

“The availability of a new treatment option that can help reduce [the] intense itching while also improving biomarkers of active liver disease is a milestone for our community,” Carol Roberts, president, The PBCers Organization, said in a news release announcing the approval. 

The most common adverse reactions with Livdelzi were headache, abdominal pain, nausea, abdominal distension, and dizziness.

The company noted that the FDA granted accelerated approval for Livdelzi based on a reduction of ALP. Improvement in survival or prevention of liver decompensation events have not been demonstrated. Continued approval of Livdelzi for PBC may be contingent on verification and description of clinical benefit in confirmatory trial(s).
 

A version of this article appeared on Medscape.com.

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