www.hivandhepatitis.com

FDA Approves AbbVie's 8-Week Mavyret Combo Pill for Hepatitis C

On August 3 the U.S.Food and Drug Administration(FDA) approved AbbVie's new pangenotypic combination pill for people with hepatitis C virus (HCV) genotypes 1 through 6, to be marketed under the brand name Mavyret. Last week the European Commission gave similar approval for the European Union, where the coformulation will be sold as Maviret.

Mavyret is a fixed-dose coformulation containing the HCV NS3/4A protease inhibitor glecaprevir and the NS5A inhibitor pibrentasvir; both drugs are being approved for the first time.

Mavyret is indicated for previously untreated people, or those treated with prior interferon-based therapy, who have HCV genotypes 1, 2, 3, 4, 5, or 6 and who either do not have liver cirrhosis or have compensated cirrhosis (Child-Pugh class A). Pangenotypic regimens that work against all genotypes have the potential to be used anywhere in the world without the need for prior genotypic testing.

In the U.S. indication, Mavyret is also approved for adults with HCV genotype 1 who were previously treated with either a NS3/4A protease inhibitor or a NS5A polymerase inhibitor, but not both. In the European indication, the new combination is not recommended for re-treatment of people who previously used either a protease inhibitoror a NS5A inhibitor.

Treatment with Mavyret involves 3 combination pills taken together once daily with food. The recommended treatment duration may be 8, 12, or 16, depending on various factors. For previously untreated people, treatment duration is 8 weeks for those without cirrhosis and 12 weeks for those with compensated cirrhosis. Mavyret is the first direct-acting antiviral regimen to be approved with an 8-week treatment duration. (Prescribing information for Harvoni [sofosbuvir/ledipasvir] says 8 weeks may be considered for treatment-naive genotype 1 patients without cirrhosis who have a low baseline HCV viral load).

Up to 95% of people with HCV in the U.S. may be eligible for treatment with Mavyret, including patients with chronic kidney disease, according to an AbbVie press release. Around three-quarters are thought to be new to treatment without cirrhosis and therefore eligible for the 8-week course.

Mavyret "offers a new therapy for the majority of HCV patients and removes many complexities of pre-treatment patient evaluation," said Stefan Zeuzem of J.W. Goethe University Hospital in Frankfurt, one of the glecaprevir/pibrentasvir trial investigators.

The new therapywas approved based on clinical trials showing that it leads to high rates of sustained virological response, or continued undetectable HCV at 12 weeks post-treatment (SVR12), which is considered a cure. AbbVie's application for approval was supported by data from 9 registrational trials that tested glecaprevir/pibrentasvir in more than 2300 patients in 27 countries, according to the company.

In the Phase 3 ENDURANCE trials, glecaprevir/pibrentasvir taken for 8 or 12 weeks cured 98% to 100% of non-cirrhotic treatment-naive and treatment-experienced patients with HCV genotypes 1, 2, 4, 5, and 6.

In ENDURANCE-3, the combo taken for either 8 or 12 weeks cured 95% of people with HCV genotype 3 and cirrhosis -- considered one the most difficult groups to treat.

Results presented at this year's EASL International Liver Congress showed that glecaprevir/pibrentasvir is highly effective in people with cirrhosis. In the EXPEDITION-1 study, 99% of patients with HCV genotypes 1, 2, 4, 5, and 6 who had early cirrhosis achieved SVR12 with 12 weeks of therapy.

As reported at last week's IAS Conference on HIV Science, glecaprevir/pibrentasvir cured 98% of people with HIV/HCV coinfection in the EXPEDITION-2 trial. In addition, the combo was highly effective for hepatitis C patients with chronic kidney disease, including those on dialysis, in EXPEDITION-4.

Glecaprevir/pibrentasvirwas generally safe and well tolerated in clinical trials, with few serious drug-related adverse events or drug discontinuations for this reason. The most common adverse events associated with the combinationwere headache, fatigue, nausea, and diarrhea, which in most cases were mild.

Mavyret is not recommended for people with significant liver function impairment (Child-Pugh class B), and it is contraindicated for those with decompensated cirrhosis (Child-Pugh class C).

The drugs in Mavyret can interact with several other medications, which could lead to sub-therapeutic drug levels or more intense side effects. It should not be used with the HIV protease inhibitor atazanavir (Reyataz) or the tuberculosis drug rifampicin. It is not recommended with a number of other medications including darunavir (Prezista), lopinavir/ritonavir (Kaletra), efavirenz (Sustiva), the anti-seizure drug carbamazepine, or St. John’s wort.

As is the case with all direct-acting antivirals, curing hepatitis C can trigger hepatitis B virus (HBV) reactivation, which can lead to severe liver injury. Anyone considering treatment with Mavyret should be screened for HBV, and those with active HBV should receive hepatitis B antiviral therapy.

AbbVie has set the price for Mavyret at $26,400 for an 8-week course, considerably lower than competing coformulations from Gilead Sciences (Epclusa and Vosevi) and Merck (Zepatier).

"This is very good news for people living with HCV in the United States. The majority of people using Mavyret will be able to complete treatment in just 8 weeks, compared with standard 12-week courses, depending on their treatment history and cirrhosis status," said Tim Horn, co-chair of the Fair Pricing Coalition. "The favorable U.S. launch price set by AbbVie should also be good news to public and private payors, resulting in fewer access barriers, a substantial increase in the number of cures, and significant progress toward HCV elimination."

8/7/17

Sources

AbbVie. European Commission Grants AbbVie's MAVIRET (glecaprevir/pibrentasvir) Marketing Authorization for the Treatment of Chronic Hepatitis C in All Major Genotypes (GT1-6). Press release. July 28, 2017.

AbbVie. AbbVie Receives U.S. FDA Approval of MAVYRET (glecaprevir/pibrentasvir) for the Treatment of Chronic Hepatitis C in All Major Genotypes (GT 1-6) in as Short as 8 Weeks. Press release. August 3, 2017.

Food and Drug Administration. FDA approves Mavyretfor Hepatitis C. Press release. August 3, 2017.

Fair Pricing Coalition Welcomes FDA Approval of AbbVie’s New Pangenotypic HCV Combination Mavyret. Press release. August 4, 2017.