AbbVie's new pangenotypic regimen combining
glecaprevir and pibrentasvir cured almost all HIV-positive people with hepatitis C co-infection in the EXPEDITION-2
study, according to a presentation on Monday at the 9th
International AIDS Society Conference on HIV Science (IAS 2017) in Paris.
Glecaprevir/pibrentasvir (Maviret) is expected to be approved by the US Food and Drug
Administration in August, and it has received a positive opinion from the scientific
committee of the European Medicines Agency (the CHMP) and should receive
European Union marketing approval within the next few months.
Direct-acting antivirals (DAAs) used in
interferon-free regimens can now cure most people with all hepatitis C virus
(HCV) genotypes in 12 weeks, and easier-to-treat people – such as previously
untreated individuals with mild liver fibrosis – can usually achieve sustained
virological response (SVR) with only 8 weeks of therapy. A shorter course of treatment could
potentially improve adherence and reduce cost.
People with HIV/HCV co-infection did not respond as well as HIV-negative individuals to
interferon-based therapy, and therefore this population has historically been
considered difficult to treat. However, studies in the DAA era have shown that
HIV-positive people generally do as well on interferon-free regimens as those
without HIV – though it is important to take into account the potential for
drug interactions between DAAs and antiretrovirals – and they are no longer
considered a "special population." Yet European and US HCV
treatment guidelines currently do not recommend shorter treatment for people with HIV and HCV co-infection.
Lacombe of Saint-Antoine Hospital in Paris presented findings from AbbVie's phase 3 EXPEDITION-2 trial, which evaluated
an 8-week regimen of glecaprevir/pibrentasvir for
people with both HIV and hepatitis C.
Glecaprevir is an HCV NS3/4A protease
inhibitor and pibrentasvir is an NS5A inhibitor. Both are pangenotypic, or
active against all HCV genotypes. The two drugs have been co-formulated in a
once-daily combination pill, to be marketed under the brand name Maviret.
Studies presented at this year's International Liver
Congress showed that glecaprevir/pibrentasvir cured 99% of people with hepatitis C with multiple HCV
genotypes, as well as 95% of people with hard-to-treat genotype 3.
EXPEDITION-2 enrolled 153 HIV-positive people with chronic hepatitis C in Europe, the United States and Russia.
More than 80% were men and the median age was approximately 45 years.
About two-thirds had HCV genotype 1 (mostly with harder-to-treat subtype 1a),
followed by genotypes 3 (17%) and 4 (11%); a small number had genotypes 2 or 6.
participants (10%) had liver cirrhosis, and most of the rest had absent or mild
fibrosis. Nearly 20% were previously treated with interferon and ribavirin, and
three had also used sofosbuvir (Sovaldi).
participants had well-controlled HIV infection with a median CD4 count of
nearly 600 cells/mm3. All but nine were on antiretroviral therapy,
and about three-quarters of treated people were taking the integrase
inhibitors raltegravir (Isentress)
or dolutegravir (Tivicay), which were shown to have minimal
interactions with glecaprevir and pibrentasvir.
without cirrhosis received glecaprevir/pibrentasvir for 8 weeks,
while those with cirrhosis were treated for 12 weeks. Everyone received the study drugs
and there was no placebo arm.
Treatment was highly effective, with 98% having
continued undetectable HCV RNA at 12 weeks post-treatment (SVR12). The cure
rate rose to 99%, with no virological failures, for people without cirrhosis
who were treated for 8 weeks.
patient with HCV genotype 3 and cirrhosis, who reported less than complete (85%)
adherence, experienced virological failure during treatment. Another
participant had missing data at 12 weeks post-treatment, but returned for care
at 24 weeks post-treatment and was found to be cured.
Glecaprevir/pibrentasvir was generally
safe and well tolerated. Adverse events were similar to those seen in studies of HIV-negative
people. One participant with cirrhosis stopped treatment
early due to an adverse event that was not considered drug-related (stroke and
brain haemorrhage). The most
common adverse events were fatigue, nausea, headache, and nose and throat
results suggest that the glecaprevir/pibrentasvir regimen could be the first
8-week, pangenotypic treatment option for HCV/HIV-1 coinfected patients without
cirrhosis," the researchers concluded.