TreatmentUpdate
213

February 2016 

Zepatier in cirrhosis

Zepatier is a fixed-dose pill containing the following two anti-HCV drugs:

  • elbasvir – 50 mg
  • grazoprevir – 100 mg

Zepatier is taken once daily with or without food.

Researchers reviewed information from six clinical trials on Zepatier to better understand its safety and effectiveness. For this review, researchers relied on data from 402 participants, focusing on extensive scarring of the liver (cirrhosis).

The presence of cirrhosis was confirmed with one of the following assessments (in most participants):

  • liver biopsy (29% of participants)
  • a specialized ultrasound scan called Fibroscan (64% of participants); a result greater than 12.5 kilopascals indicates cirrhosis
  • blood tests (7%) such as the ratio of the liver enzyme AST to the number of platelets; results greater than 2.0 are highly suggestive of cirrhosis. This test is called the AST to platelet ratio. Participants who had this test also had another blood test called Fibrotest (which measures six different proteins) to confirm the presence of cirrhosis.

Note that all participants enrolled in this study had cirrhosis without serious associated symptoms (this is called compensated cirrhosis). Their doctors classified them as Child-Pugh A—this is a scoring system that grades their chances of survival over the next two years if they do not receive treatment. In the case of Child-Pugh A, HCV-positive patients have a predicted 100% chance of surviving the next 12 months and an 85% chance of surviving for 24 months.

The average profile of participants upon entering clinical trials of Zepatier was as follows:

  • age – 56 years
  • 66% men, 34% women
  • HCV genotypes (GT) and subtypes: GT1a – 55%; GT1b – 38%; GT4 – 6%; GT6 – 1%
  • HIV co-infection – 10%
  • no previous HCV treatment – 42%

Results

Cure rates can differ depending on the sub-group studied. In this section, we look at cure rates based on factors such as treatment history, genotype and method of assessing cirrhosis.

The duration of therapy is 12 weeks unless stated otherwise.

The proportions of participants with an undetectable HCV viral load 12 weeks after the cessation of a course of Zepatier-based therapy (this milestone is referred to as a sustained virological response, written as SVR12, and participants who achieved it are considered cured) were as follows:

No previous HCV treatment

  • Zepatier – 98% cured (135 out of 138 participants)
  • Zepatier + ribavirin – 90% cured (28 out of 31 participants)

A history of HCV treatment

  • Zepatier + ribavirin for 16 to 18 weeks – 100% cured (49 out of 49 people)

Although we will not go into details, Zepatier alone for 16 to 18 weeks was less effective in treatment-experienced patients than Zepatier + ribavirin taken for the same period.

By genotype

The proportions of participants who were cured were distributed as follows:

  • Zepatier – GT1a – 96% cured (73 out of 76 people)
  • Zepatier – GT1b – 100% cured (56 out of 56 people)
  • Zepatier – GT4 – 100% cured (6 out of 6 people)

By method used to assess cirrhosis

  • Zepatier – biopsy – 100% cured (38 out of 38 people)
  • Zepatier – blood tests – 100% cured (8 out of 8 people)
  • Zepatier – Fibroscan – 98% cured (89 out of 91 people)

Focus on safety

For the safety analysis, additional data from more participants were used. The participants were distributed among the following regimens:

  • Zepatier – 264 participants
  • Zepatier + ribavirin – 193 participants
  • placebo – 22 participants

Drug-related adverse events were distributed as follows:

  • Zepatier – 42% reported side effects
  • Zepatier + ribavirin – 73% reported side effects
  • placebo – 41% reported side effects

Serious drug-related side effects were distributed as follows:

  • Zepatier – 0.4%
  • Zepatier + ribavirin – 0%
  • placebo – 0%

Deaths were distributed as follows:

  • Zepatier – one death due to cardiovascular disease
  • Zepatier + ribavirin – one death due to a vehicular accident
  • placebo – no deaths

Common side effects were distributed as follows:

Unexpected tiredness or lack of energy

  • Zepatier – 15%
  • Zepatier + ribavirin – 31%
  • placebo – 18%

Headache

  • Zepatier – 17%
  • Zepatier + ribavirin – 21%
  • placebo – 14%

Nausea

  • Zepatier – 4%
  • Zepatier + ribavirin – 14%
  • placebo – 14%

Summary

Zepatier was generally well tolerated. Common side effects were unexpected tiredness/lack of energy, headache and nausea. Side effects were usually mild or moderate in severity.

Zepatier was highly effective in participants with compensated cirrhosis, with cure rates between 97% and 100%.

—Sean R. Hosein

REFERENCE:

Jacobson I, Lawitz E, Kwo P, et al. An integrated analysis of 402 compensated cirrhotic patients with HCV genotype 1, 4 or 6 infection treated with elbasvir and grazoprevir. American Association for the Study of Liver Disease, 13-17 November 2015. Abstract 42.

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