Glecaprevir/Pibrentasvir Combination Receives FDA Approval Expanded Indication for Acute HCV

The FDA approved a label expansion for glecaprevir/pibrentasvir (Mavyret; AbbVie Inc), an oral pangenotypic direct-acting antiviral (DAA) therapy for the treatment of acute or chronic hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis in adults and pediatric patients aged 3 years and older. The expansion marks glecaprevir/pibrentasvir as the first and only indicated DAA granted approval for individuals with acute HCV, according to a news release.¹

Causes, Signs, and Symptoms of Hepatitis C Virus

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HCV is a viral infection that causes inflammation in the liver, which can lead to serious liver damage and even liver cancer or cirrhosis—an advanced scarring of the liver—if left untreated. A long-term HCV infection begins with an acute phase, which is rarely diagnosed due to a general lack of symptoms. If symptoms do occur during this phase, they can include jaundice, fatigue, nausea, fever, and muscle aches. The long-term infection is known as chronic HCV, and it typically remains asymptomatic for many years, with symptoms appearing once the virus has caused significant liver damage. Since it can take an elongated period for symptoms to appear, the US Preventive Services Task Force recommends HCV screening for all individuals aged 18 to 79 years, according to Mayo Clinic.^1,2

"The physical, emotional, and economic burden of a curable condition like hepatitis C is far too great in the United States and around the world," John Ward, MD, director at the Coalition for Global Hepatitis Elimination, said in a news release. "If treated early with safe and effective therapies, providers can cure virtually all patients with hepatitis C before it escalates to chronic disease and eventually cirrhosis or liver cancer. The public health community now has a good opportunity to cure nearly all persons to support eliminating the toll of this deadly virus. No one should die of hepatitis C."¹

Role of Glecaprevir/Pibrentasvir in HCV

Glecaprevir is an HCV NS3/4A protease inhibitor that prevents the cleavage of the HCV polyprotein, stopping viral replication. Pibrentasvir is an HCV NS5A inhibitor that prevents viral replication and assembly. As a fixed-dose combination medication, glecaprevir and pibrentasvir are indicated to provide treatment for adults and children aged 3 years and older who have either acute or chronic HCV genotypes 1, 2, 3, 4, 5, or 6, whether they have no cirrhosis or compensated cirrhosis.^3,4

Phase 3 M20-350 Clinical Trial

The label expansion for glecaprevir/pibrentasvir was approved based on data from the phase 3 multicenter, single-arm prospective M20-350 clinical trial (NCT04903626), which assessed the safety and efficacy of the combination drug for acute HCV infection over an 8-week period.¹

A total of 286 individuals with acute HCV were included in the study from 70 global locations. Individuals were given oral tablets of glecaprevir/pibrentasvir once daily for 8 weeks and were monitored for 12 weeks following the treatment's conclusion. The primary end point of the study included the percentage of individuals in the intention-to-treat (ITT) population who achieved a sustained virological response 12 weeks post-treatment (SVR12). Secondary end points included the percentage of individuals achieving SVR12 in the modified ITT-virologic failure population, as well as the percentage of individuals experiencing virologic failure during treatment and relapse after treatment in the ITT population.¹

The results demonstrated that individuals treated with glecaprevir/pibrentasvir experienced highly efficacious outcomes for acute HCV, with the most common mild to moderate adverse events being fatigue, asthenia, headache, and diarrhea.¹

"[Glecaprevir/pibrentasvir] has treated more than one million patients with HCV, but we recognize that a significant need remains for patients with acute infection," Roopal Thakkar, MD, executive vice president, research and development, and chief scientific officer from AbbVie, said in a news release. "The label expansion for [glecaprevir/pibrentasvir], coupled with the implementation of test and treat models of care, serves as a tool to support the public health community in treating more patients and bringing us closer to achieving the global 2030 elimination goal."¹

REFERENCES

1. U.S. FDA Approves Expanded Indication for AbbVie's MAVYRET® (Glecaprevir/Pibrentasvir) as First and Only Treatment for People with Acute Hepatitis C Virus. AbbVie. News release. June 11, 2025. Accessed June 11, 2025. https://www.prnewswire.com/news-releases/us-fda-approves-expanded-indication-for-abbvies-mavyret-glecaprevirpibrentasvir-as-first-and-only-treatment-for-people-with-acute-hepatitis-c-virus-302479246.html

2. Mayo Clinic. Hepatitis C. August 23, 2023. Accessed June 11, 2025. https://www.mayoclinic.org/diseases-conditions/hepatitis-c/symptoms-causes/syc-20354278

3. Mayo Clinic. Glecaprevir and pibrentasvir (oral route). Updated June 1, 2025. Accessed June 11, 2025. https://www.mayoclinic.org/drugs-supplements/glecaprevir-and-pibrentasvir-oral-route/description/drg-20406400

4. Mayo Clinic. Cirrhosis. February 22, 2025. Accessed June 11, 2025. https://www.mayoclinic.org/diseases-conditions/cirrhosis/symptoms-causes/syc-20351487