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Glecaprevir + pibrentasvir (Maviret) in HCV genotype 1 or 4 with previous treatment failure

There are limited treatment options for patients whose previous direct-acting antivirals (DAAs) have failed to cure them of chronic hepatitis C virus (HCV) infection. A combination that is in development for the treatment of many strains of HCV, including drug-resistant ones, consists of the following two drugs:

  • glecaprevir (formerly ABT-493) is a pan-genotypic inhibitor of the HCV proteins NS3/4A
  • pibrentasvir (formerly ABT-530) is active against the NS5A protein

Both of the above drugs work against a broad array of strains, or genotypes, of HCV and are co-formulated into one pill. The dose used in clinical trials is three pills once daily taken with food. This combination of drugs is a complete regimen. Results from phase I and II clinical trials show that these drugs are generally very safe and highly effective. Results from phase III studies have confirmed these trends.

In this report we will shorten the names of the drugs to G (glecaprevir) and P (pibrentasvir).

In a study called Magellan-1 part 2, researchers tested the combination of G+P for 12 or 16 weeks in participants with one of the following genotypes whose previous regimens had failed:

  • genotypes 1, 4, 5 or 6

Researchers randomly assigned participants as follows:

  • G+P for 12 consecutive weeks – 44 participants
  • G+P for 16 consecutive weeks – 47 participants

All participants were monitored for a total of 28 weeks after completing therapy.

The average profile of participants upon entering the study was as follows:

  • 70% men, 30% women
  • age – 57 years
  • body mass index (BMI; a relative indicator of fatness) – 29
  • HCV viral load – 6 million IU/mL
  • the proportion of participants with cirrhosis was 30%; no participants had symptoms of cirrhosis

Key resistance to certain classes of HCV treatments were distributed as follows:

  • none – 30%
  • NS3 only – 7%
  • NS5A only – 54%
  • NS3 + NS5A – 10%

Results

The distribution of people cured by each regimen was as follows:

  • 12-week regimen – 89% cured
  • 16-week regimen – 91% cured

Participants who had not previously used an NS5A inhibitor had cure rates of 100% with either 12 or 16 weeks of G+P.

Patients with prior failure to NS5A inhibitors and who had never previously received protease inhibitors had a 94% cure rate with 16 weeks of G+P.

—Sean R. Hosein

REFERENCE:

Poordad F, Pol S, Asatryan A, et al. Magellan-1, Part 2: glecaprevir/pibrentasvir for 12 or 16 weeks in patients with chronic HCV genotypes 1 or 4 and prior direct-acting antiviral treatment failure. In: program and abstracts of the International Liver Conference, 13-22 April 2017. Amsterdam, the Netherlands.