8-week treatment for hepatitis C with <i>Maviret</i> highly effective in people without cirrhosis

13 Apr 2018 Keith Alcorn
Originally published on www.infohep.org

An eight-week course of treatment with the combination of glecaprevir and pibrentasvir (Maviret) is highly effective in curing hepatitis C infection in people without cirrhosis, results of two real-world studies presented at the 2018 International Liver Congress in Paris show.

Preliminary results of the studies, carried out in cohorts of patients in Germany and Italy, confirm the results of clinical trials that led to the registration of Maviret. In the German study, all people without cirrhosis who started treatment were cured after eight weeks of treatment and in the Italian study 97.7% of people were cured.

“These data are important because they confirm the high cure rates of more than 98% observed in phase 3 trials,” said Professor Markus Cornberg of the Hannover Medical School, Germany, and EASL Governing Board Member. “Eight weeks of therapy is possible for all naïve, non-cirrhotic patients, regardless of genotype.”

Glecaprevir/pibrentasvir is a pangenotypic treatment for hepatitis C. An 8-week treatment course is approved for use in the European Union in all previously untreated people without cirrhosis, regardless of genotype. These recommendations are based on the results of phase 3 clinical trials and may not reflect the real-world performance of drugs.

To assess the performance of glecaprevir/pibrentasvir in German patients, Dr Thomas Berg of the University of Leipzig and colleagues looked at data from the German Hepatitis C-Registry. The registry compiles data on all German patients with hepatitis C treated by private practitioners, who make up a large proportion of physicians treating hepatitis C patients in the German healthcare system.

Individuals were included in the analysis if they did not have cirrhosis or had compensated cirrhosis and were previously untreated or had received only interferon-based treatment for hepatitis C in the past. Three hundred and seventeen eligible people have begun treatment with glecaprevir/pibrentasvir since the regimen was approved in July 2017. Of these, 271 have end-of-treatment viral load results available and 96 have 12-week post-treatment virological results available.

People receiving the 8-week Maviret regimen were predominantly male (68%) and previously untreated (90%), with a median age of 47 years. The predominant genotypes were 1a (34%) and 3 (35%). Only 7% had compensated cirrhosis and the baseline APRI score was below 1 in 79% of people, indicating good liver function and less advanced fibrosis. Twenty-six per cent were receiving opioid substitution therapy.

“It’s a very healthy cohort and it’s our impression that most patients with advanced disease are already treated in Germany. This cohort are younger and more likely to be drug users,” said Dr Berg, a view echoed by Professor Markus Cornberg.

“Most of the patients that we will need to treat in the future to eliminate hepatitis C are less advanced and easier to treat,” he told a press conference. “We want to avoid late presenters in HCV [hepatitis C virus], just as in HIV.”

Intent-to-treat analysis showed that 97% achieved a sustained virologic response 12 weeks after treatment. One person was lost to follow-up and two people discontinued treatment due to adverse events that were not study drug-related. One person suffered a serious adverse event – Meniere’s disease – thought to be possibly study drug-related. Liver enzyme elevations were very rare, affecting less than 1% of people.

In a second study, Italian investigators examined the outcomes of 639 people who received an 8-week course of treatment with glecaprevir/pibrentasvir and 84 who received a 12 or 16-week course of treatment due to cirrhosis or previous treatment history.

Almost all the 8-week treatment cohort had mild fibrosis (90% had F0-F2 fibrosis, the remainder F3 or F4). The median age of participants was 58 years and 49% were male. Six per cent had HIV co-infection.

Interim results were available for 314 of the 8-week treatment cohort patients who had week 4 post-treatment (SVR4) virological results available and final data for 44 patients with SVR12 results were available. In each group, one person had experienced post-treatment viral relapse, giving SVR4 and SVR12 results of 99.7% and 97.7% respectively. In those treated for 12 or 16 weeks 33 participants had SVR4 virological results available. In all cases, viral load was undetectable (SVR4) and in five people with 12-week post-treatment results viral load was undetectable in all cases.

There was no substantive difference in virological response according to genotype, fibrosis stage, age, baseline viral load, HIV status or size of treatment centre.