TreatmentUpdate
221

June/July 2017 

Safety and efficacy of glecaprevir + pibrentasvir (Maviret) in cases of liver or kidney transplant with chronic HCV infection

People with organ transplants and hepatitis C virus (HCV) are difficult to treat because of the potential for drug-drug interactions. An advantage of glecaprevir (G) and pibrentasvir (P) is that they have limited interactions with most transplant drugs.

In a clinical trial called Magellan-2, participants—all of whom had a liver or kidney transplant—received 12 weeks of G+P.

The average profile of 100 participants upon entering the study was as follows:

  • 75% male, 25% female
  • age – 60
  • body mass index (BMI; a relative indicator of fatness) – 26
  • HCV viral load – 6.5 million IU/mL
  • most participants (80%) had minimal or low levels of liver fibrosis (F0 to F1)
  • 34% of participants had previously been treated for HCV, mostly with interferon

The main distribution of genotypes was as follows:

  • GT 1a – 57%
  • GT 2 – 13%
  • GT 3 – 24%
  • GT 4 – 4%
  • GT 6 – 2%

The distribution of transplanted organs was as follows:

  • liver – 80%
  • kidneys – 20%

The transplantation drugs used were as follows:

  • tacrolimus
  • mycophenolate mofetil
  • cyclosporine
  • prednisone/prednisolone
  • everolimus
  • azathioprine
  • sirolimus

A majority of participants did not have any HCV drug resistance, though there were some people with resistance against HCV drugs that attacked the NS5A protein.

Results

  • 99% of participants were cured after 12 weeks
  • one participant with the sub-genotype 3a relapsed four weeks after the cessation of treatment
  • one other participant stopped making clinic visits

Adverse reactions

Two participants developed problems that could plausibly have been related to the use of G+P:

  • one participant developed a sinus inflammation
  • another participant developed temporary elevation of liver enzyme levels after treatment cessation

Common side effects reported were as follows:

  • headache – 22%
  • fatigue – 22%
  • nausea – 12%
  • itchy skin – 12%
  • diarrhea – 10%

Overall, most of these adverse effects are similar to those seen with other modern direct-acting antivirals (DAAs) and even in placebo-controlled trials among people who received placebo (such as in Polaris-1, with the combination of sofosbuvir + velpatasvir + voxilaprevir, reported later in this issue of TreatmentUpdate).

No participants died during the study.

Seriously abnormal blood test results were rare and, if they occurred, temporary in duration. Again, this is similar to reports of other DAAs in phase III clinical trials.

The combination of G+P is expected to be licensed in Canada by the end of the summer of 2017.

—Sean R. Hosein

REFERENCE:

Reau N, Kwo PY, Rhee S, et al. Magellan-2: Safety and efficacy of glecaprevir/pibrentasvir in liver or renal transplant adults with chronic hepatitis c genotype 1-6 infection. In: Program and abstracts of the International Liver Conference. 13-22 April 2017, Amsterdam, The Netherlands.