AbbVie Announces Approval of MAVIRET™ (glecaprevir/pibrentasvir) for the Treatment of Chronic Hepatitis C in All Major Genotypes (GT1-6) in Japan

NORTH CHICAGO, Ill., Sept. 27, 2017 /PRNewswire/ -- AbbVie (NYSE: ABBV), a global research and development-based biopharmaceutical company, today announced that the Japanese Ministry of Health, Labour and Welfare (MHLW) approved MAVIRET™ (glecaprevir/pibrentasvir), a once-daily, ribavirin-free treatment for adults with chronic hepatitis C virus (HCV) infection across all major genotypes (GT1-6). MAVIRET is the first and only 8-week treatment option in Japan for GT1 and GT2 HCV infected patients without cirrhosis and who are new to direct-acting antiviral (DAA) treatment,^* including those with chronic kidney disease (CKD). These patients represent the majority of people living with HCV in Japan.²  

In Japan, MAVIRET is also a 12-week option for patients infected with GT3-6, patients with specific treatment challenges including patients with compensated cirrhosis, and those with limited treatment options such as those not cured with previous DAA treatment.¹

"New pan-genotypic, ribavirin-free treatments like MAVIRET that have a short treatment duration have the potential to become a first-line HCV treatment option and will also be fundamental to addressing challenges that remain in the care of this serious and complex disease in Japan," said Hiromitsu Kumada, M.D., Director General, Department of Hepatology, Toranomon Hospital Kajigaya, Kanagawa, Japan. "High cure rates were shown in dedicated clinical trials with MAVIRET in Japanese patients, as well as a favorable tolerability profile, demonstrating the potential of MAVIRET to meet evolving unmet needs for both patients and physicians."

Japan has one of the highest rates of HCV infection in the industrialized world, with approximately 2 million people living with the disease, 97 percent of whom are infected with GT1 and GT2 chronic HCV.^2,3 Japan also has the highest prevalence of liver cancer amongst the industrialized countries with chronic hepatitis C and its complications being the leading causes.⁴

"The human, social and economic burden of HCV to individuals in Japan can be significant as the disease progresses to the later stages," said Michael Severino, M.D., executive vice president, research and development and chief scientific officer, AbbVie. "AbbVie is committed to working with health authorities to get MAVIRET to physicians and patients as quickly as possible, so that the opportunity for virologic cure in as short as 8 weeks may be a reality for the majority of people living with HCV."

Authorization is supported by data from the Phase 3 CERTAIN studies in Japanese patients and supplemented with registrational studies from AbbVie's global clinical development program for MAVIRET. With just 8 weeks of treatment, a 99 percent (n=226/229) SVR₁₂ rate was achieved across GT1 and GT2 chronic HCV infected Japanese patients without cirrhosis and who were new to DAA treatment.^*1 This high SVR₁₂ rate was achieved in patients with varied patient and viral characteristics and including those with CKD.¹ In patients not cured with previous DAA treatment, a 94 percent (n=31/33) SVR₁₂ rate was achieved with 12 weeks of treatment. The most commonly reported adverse reactions were pruritus, headache, malaise and blood bilirubin increase (none of which had an incidence greater than 5 percent).¹

MAVIRET combines two new, potent^§ direct-acting antivirals that target and inhibit proteins essential for the replication of the hepatitis C virus. The presence of more difficult-to-treat genotypes or baseline mutations that are commonly associated with resistance have been shown to have minimal impact on efficacy of MAVIRET.

Approval of MAVIRET follows priority review, designated by the Japanese MHLW to certain medicines based on the clinical usefulness of the treatment and severity of the disease. AbbVie's pan-genotypic treatment was also recently granted marketing authorization by the European Commission and approved by the U.S. Food and Drug Administration as an 8-week, pan-genotypic treatment for patients without cirrhosis and who are new to treatment.

^*Patients without previous treatment that included a DAA (direct-acting antiviral) NS3/4A protease inhibitor, NS5A inhibitor and/or NS5B polymerase inhibitor.
^**Patients who achieve a sustained virologic response at 12 weeks post treatment (SVR₁₂) are considered cured of hepatitis C.
^§Based on EC50 values of glecaprevir and pibrentasvir against full-length or chimeric replicons encoding NS3 or NS5A from laboratory strains and chimeric replicons from clinical isolates.¹

About MAVIRET™ (glecaprevir/pibrentasvir) in Japan
MAVIRET™ is approved by the the Japanese Ministry of Health, Labour and Welfare (MHLW), for the treatment of chronic hepatitis C virus (HCV) infection in adults across all major genotypes (GT1-6). MAVIRET is a pan-genotypic, once-daily, ribavirin-free treatment that combines glecaprevir (100mg), an NS3/4A protease inhibitor, and pibrentasvir (40mg), an NS5A inhibitor, dosed once-daily as three oral tablets.

In Japan, MAVIRET is an 8-week treatment option for GT1 and GT2 HCV infected patients without cirrhosis including those with chronic kidney disease (CKD) and who are new to DAA (direct-acting antiviral) treatment,^* who comprise the majority of people living with HCV. MAVIRET is also a 12-week option for patients infected with GT3-6, patients with specific treatment challenges including patients with compensated cirrhosis, and those with limited treatment options such as those not cured with previous DAA treatment.¹

Glecaprevir (GLE) was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals for HCV protease inhibitors and regimens that include protease inhibitors.

Indication in Japan

Improvement of viremia in chronic hepatitis C or compensated hepatic cirrhosis C.

Summary of Safety Information

Contraindications

MAVIRET is contraindicated in patients with a history of known hypersensitivity to the ingredients of MAVIRET, patients with severe hepatic impairment (Child-Pugh C) and patients being treated with atazanavir sulfate, atorvastatin calcium hydrate, or rifampin.

Precautions for Use

Positive result for HCV RNA should be confirmed before administering MAVIRET and decompensated cirrhosis should also be excluded by hepatic reserve or clinical symptoms.

While HCV viral load is decreased, HBV reactivation in patients who are chronically infected with HBV or patients who have a history of HBV infection (HBs-Ag negative and HBc-Ab or HBs-Ab positive) has been reported after initiation of HCV DAA treatment. Patients should be evaluated for the presence of HBV infection prior to the treatment with MAVIRET.

Glecaprevir is an inhibitor of P-gp, BCRP, and OATP1B1/1B3. Pibrentasvir is an inhibitor of P-gp, BCRP and OATP1B1. Glecaprevir is a substrate of P-gp, BCRP, and OATP1B1/1B3. Pibrentasvir is a substrate of P-gp. Co-administration of MAVIRET with these drugs may result in increased plasma concentrations of such drugs or increased or decreased plasma concentrations of MAVIRET, potentially requiring dose adjustment or clinical monitoring.

The safety of MAVIRET in pregnant women has not been established. Administration to women who are pregnant or may be pregnant must be limited to the cases in which the benefits of the treatment are deemed to outweigh the risks.

Administration to lactating women must be avoided, or breastfeeding must be avoided when administration to a lactating woman is unavoidable.

Safety and efficacy has not been established in children.

Adverse Reactions

Common adverse reactions included pruritus in 16 subjects (4.8%), headache in 14 subjects (4.2%), malaise in 10 subjects (3.0%) and blood bilirubin increased in 8 subjects (2.4%).

About AbbVie
AbbVie is a global, research-driven biopharmaceutical company committed to developing innovative advanced therapies for some of the world's most complex and critical conditions. The company's mission is to use its expertise, dedicated people and unique approach to innovation to markedly improve treatments across four primary therapeutic areas: immunology, oncology, virology and neuroscience. In more than 75 countries, AbbVie employees are working every day to advance health solutions for people around the world. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on Twitter, Facebook or LinkedIn.

For more information, please visit www.abbvie.com/HCV.

Forward-Looking Statements 
Some statements in this news release are, or may be considered, forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry.

Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," of AbbVie's 2016 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission. AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.

¹ MAVIRET [package insert]. Tokyo, Japan: AbbVie GK.
² Yu ML, Chuang WL. Treatment of chronic hepatitis C in Asia: when East meets West. J Gastroenterol Hepatal. 2009;24(3):336-45.
³ Liu GG, DiBonaventura M, Yuan Y, et al, The burden of illness for patients with viral hepatitis C: evidence from a national survey in Japan. Value Health. 2012;15(1 Suppl):565-71.
⁴ Yatsuhashi, H. Past, Present, and Future of Viral Hepatitis C in Japan. Euroasian Journal of Hepato-Gastroenterology 6, 49-51 (2016).

SOURCE AbbVie

Related Links

http://www.abbvie.com