An eight-week course of treatment with the daily oral drug glecaprevir/pibrentasvir cured chronic hepatitis C virus (HCV) infection in 98% of previously untreated patients with an asymptomatic form of cirrhosis or liver scarring known as compensated cirrhosis, according to the results of an international phase 3b clinical trial led by Weill Cornell Medicine and NewYork-Presbyterian. The simplified drug regimen may contribute to global efforts to eliminate hepatitis C infection.
Findings from the trial, known as EXPEDITION-8, were published online Nov. 2 in the Journal of Hepatology. The results led to the expanded approval by the U.S. Food and Drug Administration of the treatment regimen to include this population.
Chronic HCV infection is a significant public health threat, affecting an estimated 71 million people worldwide, including 2.4 million Americans. In the United States, only about half of the people living with the infection realize they have it, putting them at risk of progressing to liver failure and cancer, and unknowingly transmitting the virus to others. The incidence of new cases of HCV infections more than tripled from 2010 to 2016, due to the opioid crisis, as the virus can be transmitted by sharing needles when injecting drugs. HCV infections affect all generations, including baby boomers, infants born to infected mothers, and adults under 40, who are showing the highest rates of new infections.
Previously, doctors needed to assess the health of the patient’s liver with imaging tests and, in some cases, a biopsy, to determine the appropriate treatment approach. Patients with HCV infection who did not have cirrhosis could be treated with a direct oral antiviral medication for eight weeks. Those with compensated cirrhosis were treated for at least 12 weeks, according to international treatment guidelines.
“We now have a simple drug regimen that appears to cure HCV in 98% of patients, with or without cirrhosis, in one-third less time,” said lead study investigator Dr. Robert S. Brown, Jr., the Gladys and Roland Harriman Professor of Medicine, clinical chief of the Division of Gastroenterology and Hepatology, and medical director of the Center for Liver Disease and Transplantation at the NewYork-Presbyterian/Weill Cornell Medicine Medical Center. “The regimen will allow all healthcare professionals to treat patients without needing to confirm cirrhosis status.”
EXPEDITION-8 was a single-arm, open-label, phase 3b clinical trial that enrolled 343 patients in 19 countries at 94 sites, including NewYork-Presbyterian/Weill Cornell Medical Center.
The cure rate, defined as no HCV detected in the blood three months after the end of treatment, was 98%. As with the previous 12-week regimen, the drug combination was effective across all six genetic variants of the hepatitis C virus.
Only one patient experienced a relapse four weeks after completing treatment, which overall was well tolerated: The most common adverse events were fatigue, itchy skin, headache and nausea, occurring in up to 9% of patients. Serious adverse events occurred in 2% of patients, but none of these events were related to treatment.
“To meet the World Health Organization’s goal to eradicate hepatitis C infection by 2030, we need to reduce 90% of new infections and identify and cure 80 to 90% of patients who are currently infected,” said Dr. Brown. “The glecaprevir/pibrentasvir eight-week regimen will go a long way to helping us reach and cure more patients, particularly those who are at the highest risk.”
“EXPEDITION-8 reflected an international collaboration with my co-investigators, and most importantly, the patients who agreed to participate in the study,” Dr. Brown said. “They were willing to forgo a proven 12-week regimen to test a shorter course of therapy, not knowing the outcomes. We’re thankful for their bravery; they have helped all the patients that follow who can now be cured with a simpler, shorter regimen, regardless of their cirrhosis status.”
The study (NCT03089944) was sponsored by AbbVie. Robert S. Brown, Jr. has received research support from AbbVie, Bristol-Myers Squibb, Gilead, Merck and Intercept, and has acted as an advisor for AbbVie, Gilead, Intercept, Shionogi and Dova.