New antiviral combination for HCV infection in kidney disease

 

The combination of glecaprevir and pibrentasvir has been found to be both safe and effective as a treatment for hepatitis C virus (HCV) infection in patients with end-stage kidney disease, according to a paper published in the New England Journal of Medicine.

There are few treatment options available for these patients, as ribavirin can accumulate systemically in patients with severe renal impairment with serious adverse consequences such as hemolytic anemia and pruritus, and interferon has a negative side-effect profile in this population.

s-c-s/Thinkstock

“Glecaprevir, an NS3/4A protease inhibitor, and pibrentasvir, an NS5A inhibitor, exhibit potent antiviral activity across all six major HCV genotypes,” wrote Edward Gane, MD, of the Liver Unit at Auckland City Hospital, New Zealand, and coauthors. “Phase 1 studies have shown that the metabolism and clearance of both glecaprevir and pibrentasvir occur primarily in the biliary system and that renal excretion of each of the two medications is negligible; consequently, dose adjustment is typically not needed for patients with severe renal impairment.”

In this open-label phase 3 trial, 104 patients with hepatitis C infection and either compensated liver disease with severe renal impairment, dependence on dialysis, or both received 300 mg glecaprevir and 120 mg pibrentasvir daily for 12 weeks (N Engl J Med. 2017 Oct 12. doi: 10.1056/NEJMoa1704053).

The treatment was associated with a sustained virologic response in 102 patients (98%) at 12 weeks and 100 patients (96%) at 24 weeks, with no cases of virologic failure.

Of the two patients who did not have a sustained virologic response at 12 weeks, one was undergoing hemodialysis at baseline and had both compensated cirrhosis and underlying hypertension, while the other had a history of gastrointestinal tract telangiectasia and discontinued after a nonserious adverse event of diarrhea.

One-quarter of patients experienced serious adverse events, but none were deemed drug related, and there were no reports of liver decompensation. Five patients reported grade 3 hemoglobin abnormalities, but none showed abnormalities in alanine aminotransferase of grade 2 or higher.

The most common adverse events were pruritus, fatigue, and nausea, which were each reported in more than 10% of patients. The authors described this as an acceptable safety profile in a population of patients with numerous coexisting conditions. However, they noted that the absence of a placebo control group made it difficult to compare treatment-related adverse events with the underlying adverse event profile of this group of patients.

“Glecaprevir–pibrentasvir may fulfill an important unmet need; the absence of ribavirin as part of the treatment regimen minimizes the risks of treatment discontinuation and of adverse events due to anemia, which represents a considerable benefit for patients with severe renal insufficiency, since they are at increased risk for life-threatening anemia and cardiac events,” they wrote.

The study was supported by AbbVie. Twelve authors declared speakers bureau, advisory board positions, grants, or other support from AbbVie, as well as grants and funding from other pharmaceutical companies outside this work. Five authors were employees and stockholders of AbbVie.

 

 

The combination of glecaprevir and pibrentasvir has been found to be both safe and effective as a treatment for hepatitis C virus (HCV) infection in patients with end-stage kidney disease, according to a paper published in the New England Journal of Medicine.

There are few treatment options available for these patients, as ribavirin can accumulate systemically in patients with severe renal impairment with serious adverse consequences such as hemolytic anemia and pruritus, and interferon has a negative side-effect profile in this population.

s-c-s/Thinkstock

“Glecaprevir, an NS3/4A protease inhibitor, and pibrentasvir, an NS5A inhibitor, exhibit potent antiviral activity across all six major HCV genotypes,” wrote Edward Gane, MD, of the Liver Unit at Auckland City Hospital, New Zealand, and coauthors. “Phase 1 studies have shown that the metabolism and clearance of both glecaprevir and pibrentasvir occur primarily in the biliary system and that renal excretion of each of the two medications is negligible; consequently, dose adjustment is typically not needed for patients with severe renal impairment.”

In this open-label phase 3 trial, 104 patients with hepatitis C infection and either compensated liver disease with severe renal impairment, dependence on dialysis, or both received 300 mg glecaprevir and 120 mg pibrentasvir daily for 12 weeks (N Engl J Med. 2017 Oct 12. doi: 10.1056/NEJMoa1704053).

The treatment was associated with a sustained virologic response in 102 patients (98%) at 12 weeks and 100 patients (96%) at 24 weeks, with no cases of virologic failure.

Of the two patients who did not have a sustained virologic response at 12 weeks, one was undergoing hemodialysis at baseline and had both compensated cirrhosis and underlying hypertension, while the other had a history of gastrointestinal tract telangiectasia and discontinued after a nonserious adverse event of diarrhea.

One-quarter of patients experienced serious adverse events, but none were deemed drug related, and there were no reports of liver decompensation. Five patients reported grade 3 hemoglobin abnormalities, but none showed abnormalities in alanine aminotransferase of grade 2 or higher.

The most common adverse events were pruritus, fatigue, and nausea, which were each reported in more than 10% of patients. The authors described this as an acceptable safety profile in a population of patients with numerous coexisting conditions. However, they noted that the absence of a placebo control group made it difficult to compare treatment-related adverse events with the underlying adverse event profile of this group of patients.

“Glecaprevir–pibrentasvir may fulfill an important unmet need; the absence of ribavirin as part of the treatment regimen minimizes the risks of treatment discontinuation and of adverse events due to anemia, which represents a considerable benefit for patients with severe renal insufficiency, since they are at increased risk for life-threatening anemia and cardiac events,” they wrote.

The study was supported by AbbVie. Twelve authors declared speakers bureau, advisory board positions, grants, or other support from AbbVie, as well as grants and funding from other pharmaceutical companies outside this work. Five authors were employees and stockholders of AbbVie.

 

 

The combination of glecaprevir and pibrentasvir has been found to be both safe and effective as a treatment for hepatitis C virus (HCV) infection in patients with end-stage kidney disease, according to a paper published in the New England Journal of Medicine.

There are few treatment options available for these patients, as ribavirin can accumulate systemically in patients with severe renal impairment with serious adverse consequences such as hemolytic anemia and pruritus, and interferon has a negative side-effect profile in this population.

s-c-s/Thinkstock

“Glecaprevir, an NS3/4A protease inhibitor, and pibrentasvir, an NS5A inhibitor, exhibit potent antiviral activity across all six major HCV genotypes,” wrote Edward Gane, MD, of the Liver Unit at Auckland City Hospital, New Zealand, and coauthors. “Phase 1 studies have shown that the metabolism and clearance of both glecaprevir and pibrentasvir occur primarily in the biliary system and that renal excretion of each of the two medications is negligible; consequently, dose adjustment is typically not needed for patients with severe renal impairment.”

In this open-label phase 3 trial, 104 patients with hepatitis C infection and either compensated liver disease with severe renal impairment, dependence on dialysis, or both received 300 mg glecaprevir and 120 mg pibrentasvir daily for 12 weeks (N Engl J Med. 2017 Oct 12. doi: 10.1056/NEJMoa1704053).

The treatment was associated with a sustained virologic response in 102 patients (98%) at 12 weeks and 100 patients (96%) at 24 weeks, with no cases of virologic failure.

Of the two patients who did not have a sustained virologic response at 12 weeks, one was undergoing hemodialysis at baseline and had both compensated cirrhosis and underlying hypertension, while the other had a history of gastrointestinal tract telangiectasia and discontinued after a nonserious adverse event of diarrhea.

One-quarter of patients experienced serious adverse events, but none were deemed drug related, and there were no reports of liver decompensation. Five patients reported grade 3 hemoglobin abnormalities, but none showed abnormalities in alanine aminotransferase of grade 2 or higher.

The most common adverse events were pruritus, fatigue, and nausea, which were each reported in more than 10% of patients. The authors described this as an acceptable safety profile in a population of patients with numerous coexisting conditions. However, they noted that the absence of a placebo control group made it difficult to compare treatment-related adverse events with the underlying adverse event profile of this group of patients.

“Glecaprevir–pibrentasvir may fulfill an important unmet need; the absence of ribavirin as part of the treatment regimen minimizes the risks of treatment discontinuation and of adverse events due to anemia, which represents a considerable benefit for patients with severe renal insufficiency, since they are at increased risk for life-threatening anemia and cardiac events,” they wrote.

The study was supported by AbbVie. Twelve authors declared speakers bureau, advisory board positions, grants, or other support from AbbVie, as well as grants and funding from other pharmaceutical companies outside this work. Five authors were employees and stockholders of AbbVie.