SAN FRANCISCO — An 8-week regimen of the combination of glecaprevir plus pibrentasvir (Mavyret, AbbVie) can eliminate most genotypes of the hepatitis C virus in treatment-naïve patients with compensated cirrhosis, results from the EXPEDITION-8 trial show.
The shorter course of therapy should decrease costs and increase adherence, said Robert Brown, MD, from the Center for Liver Disease and Transplantation at the New York–Presbyterian, Weill Cornell Medical Center in New York City.
"The longer the duration required, the higher the likelihood that patients won't complete it," he told Medscape Medical News.
An 8-week regimen of glecaprevir plus pibrentasvir has been approved for all genotypes of hepatitis C in patients without cirrhosis, but for patients with cirrhosis, the combination is currently labeled as a 12-week regimen by the US Food and Drug Administration.
In previous studies of patients with cirrhosis, there is only one report of virologic failure, Brown reported here at The Liver Meeting 2018. This prompted his team to launch EXPEDITION-8 to see if a shorter regimen would be effective in patients with cirrhosis.
In their study, Brown and his colleagues assessed 280 treatment-naïve patients infected with all genotypes of the virus, except genotype 3, which is more resistant to direct-acting antiviral drugs.
Half of the patients had a platelet count below 1000 cells/L at study entry, average Child–Pugh score was 5, and 60% of the patients were male. The majority of patients were white, but 10% were black, 13% were Latino, and 10% were Asian.
Most of the study population — 82% — had the genotype 1 subtype of the hepatitis C virus, 9% had genotype 2, 5% had genotype 4, less than 1% had genotype 5, and 3% had genotype 6.
| Table. Baseline Measures in the Study Population | ||
| Measure | Median | Range |
|---|---|---|
| Hepatitis C RNA level (log10 IU/mL) | 6.3 | 3.4–7.5 |
| FibroScan score (kPa) | 20.7 | 2.5–70.6 |
| Platelet count (× 109 cells/L) | 152 | 42–788 |
| Total bilirubin level (mg/dL) | 0.7 | 0.2–2.4 |
| Albumin level (g/dL) | 4.2 | 2.7–5.1 |
The most common adverse events were pruritus (9%), fatigue (9%), headache (7%), and nausea (6%). Most were mild and none led to the discontinuation of treatment. There were five serious adverse events, but none of those were deemed to be related to the drug.
All five patients who missed their 12-week follow-up visit had an undetectable viral load at their previous visit. All patients who completed the 8 weeks of therapy were cured.
Of the two patients who stopped treatment early, one was cured.
These encouraging findings broaden the proportion of patients with hepatitis C who are eligible for an 8-week regimen of glecaprevir plus pibrentasvir to about 85% in the United States, said Brown, who then broke down that estimate.
About 74% of patients with hepatitis C patients are treatment-naïve and don't have cirrhosis, so they are already eligible for the 8-week course of treatment, he explained. And about 11% are treatment-naïve, have cirrhosis, and likely have the genotype 1 hepatitis C virus.
After initial success in the study population, the team expanded the trial to include 60 patients with genotype 3 hepatitis C; they plan to report those results in the spring, Brown said.
If the 8-week regimen works as well in patients with the genotype 3 subtype, about 90% of people with hepatitis C would be eligible for an 8-week regimen, he reported.
Most treatment-experienced patients would still be prescribed a 12-week regimen because they likely need aggressive therapy, he pointed out. A small number of patients whose only previous treatment was pegylated interferon and ribavirin might also be eligible for an 8-week regimen of glecaprevir plus pibrentasvir.
Patients with decompensated cirrhosis should not be treated with protease inhibitors, such as glecaprevir. Instead, they should be treated with polymerase inhibitor — namely sofosbuvir (Sovaldi, Gilead), Brown said.
It is unlikely that the treatment regimen will get any shorter than 8 weeks because cure rates seem to drop after that. With some of the earlier regimens, one-third of patients were cured with just 4 weeks of therapy, but it was difficult to predict who would be cured. "Without the ability to predict, we're not willing to give up two-thirds of our cure rate to save 4 weeks of therapy," he explained.
The way the glecaprevir plus pibrentasvir combination is used differs by location, he said. In places with enough resources, it will still be important to screen patients with cirrhosis for cancer.
If the data for genotype 3 are solid, providers in poorer, rural areas might simply give the pills to anyone who tests positive for hepatitis C. "If they don't come back, we will still have a very high chance of achieving cure in all patients," Brown said.
The only other combination approved for a duration of 8 weeks is ledipasvir plus sofosbuvir (Harvoni, Gilead). But that regimen is limited to patients with genotype 1 hepatitis C, no cirrhosis, and a viral load below 6 million IU/mL.
These 8-week findings "certainly reassure us that this is going to be effective therapy in compensated cirrhosis," said Jordan Feld, MD, from the Francis Family Liver Clinic at the Toronto General Hospital.
The genotype 3 data will be important for clinicians because unless the combination proves to be as effective for that subtype, the genotype of each patient will have to be confirmed before the duration of glecaprevir and pibrentasvir is set.
"The one downslide of this is that before you had a very simple model — cirrhosis or no cirrhosis," Feld told Medscape Medical News. "Genotype was irrelevant."
Brown reports financial relationships with AbbVie, Gilead, and Merck. Feld reports relationships with AbbVie, Gilead, Merck, Enanta, and ContraVir.
The Liver Meeting 2018: American Association for the Study of Liver Diseases (AASLD): Abstract LB-7. Presented November 13, 2018.
Follow Medscape Gastroenterology on Twitter @MedscapeGastro and Laird Harrison @LairdH
Medscape Medical News © 2018
Cite this: Hep C Therapy Can Be Shortened to 8 Weeks, Despite Cirrhosis - Medscape - Nov 14, 2018.
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