Mavyret Approved as Eight-Week HCV Treatment Regimen, Including for Those With Mild Cirrhosis

In a major milestone, AbbVie's new hepatitis C (HCV) drug combination, glecaprevir and pibrentasvir (Mavyret), has been approved for patients of any genotype with a treatment duration of only eight weeks -- four weeks less than most other direct-acting antiviral (DAA) regimens.

Although the eight-week regimen was approved only for patients who have never been treated before (so-called treatment-naive patients), it was approved for all six hepatitis C genotypes and for patients with mild cirrhosis.

In 2014, Gilead's two-drug combo sofosbuvir/ledipasvir (Harvoni) was approved as an eight-week treatment in certain limited patient populations with uncomplicated hepatitis C infections, such as treatment-naive genotype 1 patients, who are generally thought to be among the easiest to treat.

Yet, the U.S. Food and Drug Administration also imposed certain restrictions on sofosbuvir/ledipasvir when prescribed as an eight-week regimen rather than the typical 12, making it practically difficult for prescribers to opt for eight weeks even for ideal candidates. For example, sofosbuvir/ledipasvir was approved for treatment-naive candidates without cirrhosis and with low levels of HCV RNA in their blood prior to treatment -- yet, mandating a test for HCV RNA created an extra step that may have discouraged eight-week prescriptions, especially when 12 weeks is considered very safe.

AbbVie's regimen, meanwhile, has been approved as an eight-week treatment for any patient who has never previously been treated and has no major complications such as extreme liver damage or kidney disease. It is comprised of a pangenotypic NS3/4A protease inhibitor (glecaprevir) and a pangenotypic NS5A inhibitor (pibrentasvir). Unlike Gilead's regimens, it does not make use of a non-nucleoside inhibitor, or "nuke," backbone.

Approval was based on cure data from clinical trials that enrolled about 2,300 adults of all genotypes, with and without cirrhosis. Regardless of the length of treatment (eight, 12 or 16 weeks), between 92% and 100% of patients were cured.

The duration of treatment is important because it improves patient adherence and makes the overall course of treatment less of a financial burden for patients and insurance providers. In general, the newer generations of DAAs have wholesale prices set above $50,000, sometimes up to $100,000. The first blockbuster DAA, Gilead's sofosbuvir, famously cost $1,000 per pill.

Meanwhile, AbbVie set the 12-week wholesale acquisition price of glecaprevir/pibrentasvir at $39,600, making the price for eight weeks of treatment only $26,400 -- far cheaper than the comparable pangenotypic regimens from Gilead, sofosbuvir/velpatasvir/voxilaprevir (Vosevi) and sofosbuvir/velpatasvir (Epclusa), both of which cost $74,760 for 12 weeks.

AbbVie's pricing decision prompted applause from the Fair Pricing Coalition (FPC). In a recently released statement, FPC's Tim Horn described glecaprevir/pibrentasvir's price point as "very good news for people living with HCV in the United States," noting that a majority of people prescribed glecaprevir/pibrentasvir will be able to complete treatment in eight weeks rather than 12. The relatively discounted price of AbbVie's regimen is likely to lower treatment barriers and get more people on treatment and cured, Horn said in prepared remarks.

AbbVie's two-drug combo was also approved in adults with genotype 1 infection who previously failed treatment with a regimen containing either an NS5A or an NS3/4A. It cannot be used in patients who have been previously treated with a regimen containing both. Still, considering that many patients have been treated with a combination nuke and NS5A, the new drug will likely become an important salvage therapy in the armamentarium of hepatitis C medications.