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PHOENIX — , supporting the drug’s benefits for the large percentage of patients who may fail to improve with or become intolerant of standard PBC therapy.
“This pooled analysis demonstrated that seladelpar treatment for up to 6 months reduced pruritus to a greater extent vs placebo in patients with PBC who had moderate-to-severe pruritus at baseline,” said senior author Marlyn J. Mayo, MD, AGAF, of the Division of Digestive and Liver Diseases, University of Texas Southwestern, Dallas, in presenting the findings at the American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.
In PBC, a rare, chronic liver disease that can progressively destroy the intrahepatic bile ducts, ursodeoxycholic acid (UDCA) has remained a highly effective standard of care; however, up to 40% of patients either fail to achieve a biochemical response or develop intolerances to the therapy.
Seladelpar, in addition to improving measures of PBC disease including liver function tests and markers of cholestasis, has been shown in clinical trials to reduce the symptoms of pruritus and related sleep disturbances.
The drug is approved by the FDA for the treatment of PBC in combination with UDCA when patients fail to have an adequate response to UDCA alone, or as monotherapy when patients are intolerant to UDCA.
With pruritus, or itching, representing a key detrimental symptom of PBC and affecting as many as 70% of patients, Mayo and her colleagues conducted a pooled analysis of two phase 3, placebo-controlled trials, the ENHANCE and RESPONSE trials, in order to delve deeper into the specifics of how seladelpar improves itching.
The studies both involved patients with PBC and moderate-to-severe pruritus at baseline who had an inadequate response to UDCA and received seladelpar as add-on therapy to the drug, if tolerant of UDCA.
In the ENHANCE trial, patients were randomized 1:1:1 to daily oral seladelpar 5 mg, 10 mg, or placebo for 52 weeks, and in the RESPONSE trial, they were randomized 2:1 to daily oral seladelpar 10 mg or placebo for 52 weeks.
The ENHANCE trial was terminated early with key endpoints amended to 3 months.
In total, the analysis included 126 patients with a pruritus numerical rating scale (NRS) score of at least 4 at baseline (indicative of moderate-to-severe itch), with 76 patients receiving seladelpar 10 mg and 50 receiving placebo.
Patients in the two groups had a mean age of 53 years; 96% were female; their mean age at PBC diagnosis was 47 years; and itch scores — including the NRS, PBC-40 itch domain, and 5-D itch scale scores — were similar across the treatment and placebo groups at baseline.
After 6 months, patients treated with seladelpar reported greater improvements than those receiving placebo across all measures.
For changes in pruritus NRS through month 6, greater decreases were observed with seladelpar 10 mg at months 1, 3, and 6, with a 6-month decrease from baseline of 3.33 in the seladelpar group vs 1.77 with placebo (P < .01).
For PBC-40 itch domain scores, the mean reduction from baseline at 6 months was 2.41 vs 0.98, although significance was lost at month 6 due to a reduction in numbers.
For the 5-D itch total scores, the mean reduction from baseline to 6 months was 5.09 vs 1.70 (P < .0001).
And for the 5-D itch degree, the domain scores were also improved with seladelpar (mean reduction from baseline to 6 months of 1.08 vs 0.47; P = .01).
Patients treated with seladelpar also showed greater improvement in the sleep disturbances that can accompany pruritus, including on the 5-D itch Sleep Item scale (P < .01 at 6 months) and the PBC-40 Sleep Disturbance Item (P < .0001 at 1 month vs placebo; not significant at 6 months).
There were no significant differences between the groups in safety or tolerability profiles overall, with any adverse events occurring in 57 of the 76 (75%) patients receiving seladelpar and 40 of 50 (80%) receiving placebo.
Grade 3 or higher adverse events occurred in 8% of seladelpar and 12% of placebo patients, and pruritus-specific adverse events occurred in 8% and 14%, respectively.
“We found that improvement versus placebo was evident at month 1 of treatment and was sustained through month 6 using three different measures of pruritus,” Mayo said.
“And improvements in sleep disturbance were also seen in patients receiving seladelpar vs placebo through month 6 using two different measures of (5-D itch and PBC-40).”
Mayo noted that seladelpar is currently the only FDA-approved second-line therapy for people who have not had an adequate biochemical response or cannot tolerate UDCA.
While the drug is not likely at a point where it could be positioned as a first-line itch therapy, Mayo suggested that, for those who have had a poor response to UDCA, “I think it makes sense to start with something like this and then see how patients’ itching is affected by the drug.”
“It’s possible it could help avoid having to add yet another drug to treat the itch, and the hope is that this will help reduce the issue of polypharmacy.”
Commenting on the study, Luis F. Lara, MD, Division Chief of Digestive Diseases at the University of Cincinnati in Cincinnati, who co-moderated the session, underscored the need for treatment among patients who fail to respond to standard therapy.
“I think this is very important research,” he told GI & Hepatology News. “First, the fact that so many patients suffer their pruritus without any therapy is actually disturbing.”
“And the fact that this medication seems to be extremely effective in treating this, likely tremendously affecting patients’ quality of life, is something to really highlight.”
Lara noted that the findings raise the question of “whether this should be considered earlier in the disease process, rather than waiting to use it as a second-line therapy, when pruritus has already become significant.”
Akwi W. Asombang, MD, interventional enterologist at Massachusetts General Hospital and associate professor of medicine at Harvard Medical School in Boston, who was also a co-moderator, agreed that “having a disease process that results in itching all the time can represent profound discomfort and a significant quality of life issue.”
“So, to have a drug that could minimize or alleviate that process could be huge,” Asombang told GI & Hepatology News.
The ENHANCE and RESPONSE trials were funded by Gilead Sciences. Mayo’s disclosures included consulting and/or other relationships with CymaBay Therapeutics, GSK, Intra-Sana, Ipsen, Mirum Pharma, and Target PharmaSolutions. Lara disclosed having a relationship with AbbVie. Asombang reported having no disclosures.
A version of this article appeared on Medscape.com .
PHOENIX — , supporting the drug’s benefits for the large percentage of patients who may fail to improve with or become intolerant of standard PBC therapy.
“This pooled analysis demonstrated that seladelpar treatment for up to 6 months reduced pruritus to a greater extent vs placebo in patients with PBC who had moderate-to-severe pruritus at baseline,” said senior author Marlyn J. Mayo, MD, AGAF, of the Division of Digestive and Liver Diseases, University of Texas Southwestern, Dallas, in presenting the findings at the American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.
In PBC, a rare, chronic liver disease that can progressively destroy the intrahepatic bile ducts, ursodeoxycholic acid (UDCA) has remained a highly effective standard of care; however, up to 40% of patients either fail to achieve a biochemical response or develop intolerances to the therapy.
Seladelpar, in addition to improving measures of PBC disease including liver function tests and markers of cholestasis, has been shown in clinical trials to reduce the symptoms of pruritus and related sleep disturbances.
The drug is approved by the FDA for the treatment of PBC in combination with UDCA when patients fail to have an adequate response to UDCA alone, or as monotherapy when patients are intolerant to UDCA.
With pruritus, or itching, representing a key detrimental symptom of PBC and affecting as many as 70% of patients, Mayo and her colleagues conducted a pooled analysis of two phase 3, placebo-controlled trials, the ENHANCE and RESPONSE trials, in order to delve deeper into the specifics of how seladelpar improves itching.
The studies both involved patients with PBC and moderate-to-severe pruritus at baseline who had an inadequate response to UDCA and received seladelpar as add-on therapy to the drug, if tolerant of UDCA.
In the ENHANCE trial, patients were randomized 1:1:1 to daily oral seladelpar 5 mg, 10 mg, or placebo for 52 weeks, and in the RESPONSE trial, they were randomized 2:1 to daily oral seladelpar 10 mg or placebo for 52 weeks.
The ENHANCE trial was terminated early with key endpoints amended to 3 months.
In total, the analysis included 126 patients with a pruritus numerical rating scale (NRS) score of at least 4 at baseline (indicative of moderate-to-severe itch), with 76 patients receiving seladelpar 10 mg and 50 receiving placebo.
Patients in the two groups had a mean age of 53 years; 96% were female; their mean age at PBC diagnosis was 47 years; and itch scores — including the NRS, PBC-40 itch domain, and 5-D itch scale scores — were similar across the treatment and placebo groups at baseline.
After 6 months, patients treated with seladelpar reported greater improvements than those receiving placebo across all measures.
For changes in pruritus NRS through month 6, greater decreases were observed with seladelpar 10 mg at months 1, 3, and 6, with a 6-month decrease from baseline of 3.33 in the seladelpar group vs 1.77 with placebo (P < .01).
For PBC-40 itch domain scores, the mean reduction from baseline at 6 months was 2.41 vs 0.98, although significance was lost at month 6 due to a reduction in numbers.
For the 5-D itch total scores, the mean reduction from baseline to 6 months was 5.09 vs 1.70 (P < .0001).
And for the 5-D itch degree, the domain scores were also improved with seladelpar (mean reduction from baseline to 6 months of 1.08 vs 0.47; P = .01).
Patients treated with seladelpar also showed greater improvement in the sleep disturbances that can accompany pruritus, including on the 5-D itch Sleep Item scale (P < .01 at 6 months) and the PBC-40 Sleep Disturbance Item (P < .0001 at 1 month vs placebo; not significant at 6 months).
There were no significant differences between the groups in safety or tolerability profiles overall, with any adverse events occurring in 57 of the 76 (75%) patients receiving seladelpar and 40 of 50 (80%) receiving placebo.
Grade 3 or higher adverse events occurred in 8% of seladelpar and 12% of placebo patients, and pruritus-specific adverse events occurred in 8% and 14%, respectively.
“We found that improvement versus placebo was evident at month 1 of treatment and was sustained through month 6 using three different measures of pruritus,” Mayo said.
“And improvements in sleep disturbance were also seen in patients receiving seladelpar vs placebo through month 6 using two different measures of (5-D itch and PBC-40).”
Mayo noted that seladelpar is currently the only FDA-approved second-line therapy for people who have not had an adequate biochemical response or cannot tolerate UDCA.
While the drug is not likely at a point where it could be positioned as a first-line itch therapy, Mayo suggested that, for those who have had a poor response to UDCA, “I think it makes sense to start with something like this and then see how patients’ itching is affected by the drug.”
“It’s possible it could help avoid having to add yet another drug to treat the itch, and the hope is that this will help reduce the issue of polypharmacy.”
Commenting on the study, Luis F. Lara, MD, Division Chief of Digestive Diseases at the University of Cincinnati in Cincinnati, who co-moderated the session, underscored the need for treatment among patients who fail to respond to standard therapy.
“I think this is very important research,” he told GI & Hepatology News. “First, the fact that so many patients suffer their pruritus without any therapy is actually disturbing.”
“And the fact that this medication seems to be extremely effective in treating this, likely tremendously affecting patients’ quality of life, is something to really highlight.”
Lara noted that the findings raise the question of “whether this should be considered earlier in the disease process, rather than waiting to use it as a second-line therapy, when pruritus has already become significant.”
Akwi W. Asombang, MD, interventional enterologist at Massachusetts General Hospital and associate professor of medicine at Harvard Medical School in Boston, who was also a co-moderator, agreed that “having a disease process that results in itching all the time can represent profound discomfort and a significant quality of life issue.”
“So, to have a drug that could minimize or alleviate that process could be huge,” Asombang told GI & Hepatology News.
The ENHANCE and RESPONSE trials were funded by Gilead Sciences. Mayo’s disclosures included consulting and/or other relationships with CymaBay Therapeutics, GSK, Intra-Sana, Ipsen, Mirum Pharma, and Target PharmaSolutions. Lara disclosed having a relationship with AbbVie. Asombang reported having no disclosures.
A version of this article appeared on Medscape.com .
PHOENIX — , supporting the drug’s benefits for the large percentage of patients who may fail to improve with or become intolerant of standard PBC therapy.
“This pooled analysis demonstrated that seladelpar treatment for up to 6 months reduced pruritus to a greater extent vs placebo in patients with PBC who had moderate-to-severe pruritus at baseline,” said senior author Marlyn J. Mayo, MD, AGAF, of the Division of Digestive and Liver Diseases, University of Texas Southwestern, Dallas, in presenting the findings at the American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.
In PBC, a rare, chronic liver disease that can progressively destroy the intrahepatic bile ducts, ursodeoxycholic acid (UDCA) has remained a highly effective standard of care; however, up to 40% of patients either fail to achieve a biochemical response or develop intolerances to the therapy.
Seladelpar, in addition to improving measures of PBC disease including liver function tests and markers of cholestasis, has been shown in clinical trials to reduce the symptoms of pruritus and related sleep disturbances.
The drug is approved by the FDA for the treatment of PBC in combination with UDCA when patients fail to have an adequate response to UDCA alone, or as monotherapy when patients are intolerant to UDCA.
With pruritus, or itching, representing a key detrimental symptom of PBC and affecting as many as 70% of patients, Mayo and her colleagues conducted a pooled analysis of two phase 3, placebo-controlled trials, the ENHANCE and RESPONSE trials, in order to delve deeper into the specifics of how seladelpar improves itching.
The studies both involved patients with PBC and moderate-to-severe pruritus at baseline who had an inadequate response to UDCA and received seladelpar as add-on therapy to the drug, if tolerant of UDCA.
In the ENHANCE trial, patients were randomized 1:1:1 to daily oral seladelpar 5 mg, 10 mg, or placebo for 52 weeks, and in the RESPONSE trial, they were randomized 2:1 to daily oral seladelpar 10 mg or placebo for 52 weeks.
The ENHANCE trial was terminated early with key endpoints amended to 3 months.
In total, the analysis included 126 patients with a pruritus numerical rating scale (NRS) score of at least 4 at baseline (indicative of moderate-to-severe itch), with 76 patients receiving seladelpar 10 mg and 50 receiving placebo.
Patients in the two groups had a mean age of 53 years; 96% were female; their mean age at PBC diagnosis was 47 years; and itch scores — including the NRS, PBC-40 itch domain, and 5-D itch scale scores — were similar across the treatment and placebo groups at baseline.
After 6 months, patients treated with seladelpar reported greater improvements than those receiving placebo across all measures.
For changes in pruritus NRS through month 6, greater decreases were observed with seladelpar 10 mg at months 1, 3, and 6, with a 6-month decrease from baseline of 3.33 in the seladelpar group vs 1.77 with placebo (P < .01).
For PBC-40 itch domain scores, the mean reduction from baseline at 6 months was 2.41 vs 0.98, although significance was lost at month 6 due to a reduction in numbers.
For the 5-D itch total scores, the mean reduction from baseline to 6 months was 5.09 vs 1.70 (P < .0001).
And for the 5-D itch degree, the domain scores were also improved with seladelpar (mean reduction from baseline to 6 months of 1.08 vs 0.47; P = .01).
Patients treated with seladelpar also showed greater improvement in the sleep disturbances that can accompany pruritus, including on the 5-D itch Sleep Item scale (P < .01 at 6 months) and the PBC-40 Sleep Disturbance Item (P < .0001 at 1 month vs placebo; not significant at 6 months).
There were no significant differences between the groups in safety or tolerability profiles overall, with any adverse events occurring in 57 of the 76 (75%) patients receiving seladelpar and 40 of 50 (80%) receiving placebo.
Grade 3 or higher adverse events occurred in 8% of seladelpar and 12% of placebo patients, and pruritus-specific adverse events occurred in 8% and 14%, respectively.
“We found that improvement versus placebo was evident at month 1 of treatment and was sustained through month 6 using three different measures of pruritus,” Mayo said.
“And improvements in sleep disturbance were also seen in patients receiving seladelpar vs placebo through month 6 using two different measures of (5-D itch and PBC-40).”
Mayo noted that seladelpar is currently the only FDA-approved second-line therapy for people who have not had an adequate biochemical response or cannot tolerate UDCA.
While the drug is not likely at a point where it could be positioned as a first-line itch therapy, Mayo suggested that, for those who have had a poor response to UDCA, “I think it makes sense to start with something like this and then see how patients’ itching is affected by the drug.”
“It’s possible it could help avoid having to add yet another drug to treat the itch, and the hope is that this will help reduce the issue of polypharmacy.”
Commenting on the study, Luis F. Lara, MD, Division Chief of Digestive Diseases at the University of Cincinnati in Cincinnati, who co-moderated the session, underscored the need for treatment among patients who fail to respond to standard therapy.
“I think this is very important research,” he told GI & Hepatology News. “First, the fact that so many patients suffer their pruritus without any therapy is actually disturbing.”
“And the fact that this medication seems to be extremely effective in treating this, likely tremendously affecting patients’ quality of life, is something to really highlight.”
Lara noted that the findings raise the question of “whether this should be considered earlier in the disease process, rather than waiting to use it as a second-line therapy, when pruritus has already become significant.”
Akwi W. Asombang, MD, interventional enterologist at Massachusetts General Hospital and associate professor of medicine at Harvard Medical School in Boston, who was also a co-moderator, agreed that “having a disease process that results in itching all the time can represent profound discomfort and a significant quality of life issue.”
“So, to have a drug that could minimize or alleviate that process could be huge,” Asombang told GI & Hepatology News.
The ENHANCE and RESPONSE trials were funded by Gilead Sciences. Mayo’s disclosures included consulting and/or other relationships with CymaBay Therapeutics, GSK, Intra-Sana, Ipsen, Mirum Pharma, and Target PharmaSolutions. Lara disclosed having a relationship with AbbVie. Asombang reported having no disclosures.
A version of this article appeared on Medscape.com .
FROM ACG 2025