Enanta Pharmaceuticals, Inc. Announces Approval Of VIEKIRAX (Ombitasvir/Paritaprevir/Ritonavir Tablets) In Japan For The Treatment Of Genotype 1 Chronic Hepatitis C

WATERTOWN, Mass.--(BUSINESS WIRE)--Enanta Pharmaceuticals, Inc., (NASDAQ:ENTA) a research and development-focused biotechnology company dedicated to creating small molecule drugs for viral infections and liver diseases, today announced that the Japanese Ministry of Health, Labour and Welfare (MHLW) approved AbbVie’s VIEKIRAX® (ombitasvir/paritaprevir/ritonavir), as a new interferon-free and ribavirin-free treatment option for adult patients in Japan with chronic genotype 1 (GT1) hepatitis C virus (HCV) infection, including those with compensated liver cirrhosis.¹ VIEKIRAX consists of two-direct-acting antiviral (2-DAA), fixed-dose tablets containing paritaprevir/ritonavir with ombitasvir. VIEKIRAX is approved in Japan using once daily dosing for 12 weeks for GT1 HCV patients.

“The approval of VIEKIRAX in Japan marks another major territory in which a regimen containing paritaprevir is approved”

Paritaprevir is Enanta’s lead protease inhibitor identified within the ongoing Enanta-AbbVie collaboration and is one of the two DAAs in AbbVie’s VIEKIRAX.

Japan has one of the highest rates of hepatitis C infection in the industrialized world, with approximately 1.5 to 2 million people living with HCV.^{2, 3} Genotype 1 is the most common HCV genotype in Japan with 60 to 70 percent of patients infected and, of those, about 95 percent are infected with the genotype 1b (GT1b) sub-type.⁴

Enanta expects to earn and receive a $30 million milestone payment in the quarter ending December 31, 2015 upon price reimbursement approval of VIEKIRAX in Japan. In addition, forty five percent of AbbVie’s net sales of the 2-DAA regimen in Japan will be included in the worldwide paritaprevir net sales on which Enanta is eligible to receive annually tiered royalties, ranging from the low double digits up to twenty percent. AbbVie is responsible for all worldwide development and commercialization of VIEKIRAX and other HCV treatment regimens containing paritaprevir. Paritaprevir/ritonavir and ombitasvir, AbbVie’s NS5A inhibitor, are also included in AbbVie’s 3-DAA VIEKIRA PAK™ regimen, which was approved in the U.S. in late 2014 for patients with GT1 HCV infection. VIEKIRAX was first approved under that name in Europe in January 2015.

“The approval of VIEKIRAX in Japan marks another major territory in which a regimen containing paritaprevir is approved,” stated Jay R. Luly, Ph.D., President and CEO. “VIEKIRAX offers HCV patients in Japan an all-oral, once daily treatment option that has demonstrated high cure rates. We are proud that paritaprevir is part of this regimen.”

The approval was supported by the phase 3 GIFT-I study.¹ An overall 95 percent (n=140/148) of treatment-naïve and 94 percent (n=102/109) of treatment-experienced GT1b HCV infected patients achieved SVR₁₂ with VIEKIRAX.¹

The primary endpoint was achieved, demonstrating 95 percent (n=106/112) SVR₁₂ in a sub-group of treatment-naïve, non-cirrhotic, adult, GT1b HCV infected Japanese patients who were eligible for therapy with interferon (IFN) and had a high viral load. A secondary endpoint in GT1b HCV patients with compensated cirrhosis achieved 91 percent (n=38/42) SVR₁₂.⁵

Across all treatment arms, three patients (n=3/363) experienced on-treatment virologic failure, eight patients (n=8/354) experienced post-treatment relapse and three patients discontinued treatment due to adverse events. The most commonly reported adverse events (>5 percent in any arm) were nasopharyngitis, headache, peripheral edema, nausea, pyrexia and decreased platelet count.⁵

In April 2015, the Japanese MHLW granted AbbVie priority review for VIEKIRAX on the basis of clinical usefulness of the treatment and recognizing the severity and unmet need of HCV in Japan.

About the GIFT-I Study⁵

GIFT-I comprises 363 patients in two sub-studies, one of which had two arms (Arms A and B).

In sub-study 1,321 genotype 1b (GT1b) patients without cirrhosis, both treatment-naïve and interferon (IFN) [with or without ribavirin (RBV)] treatment-experienced, were randomized to receive either ombitasvir/paritaprevir/ritonavir (Arm A) [OBV/PTV/r] or placebo (Arm B) [2:1 randomization ratio, stratified by treatment history, past response, viral load and IFN eligibility]. Patients initially randomized to placebo (Arm B) then received OBV/PTV/r for an additional 12 weeks of open-label treatment. Sustained virologic response was assessed 12 weeks post-treatment (SVR₁₂) as a primary efficacy endpoint in a sub-group of previously untreated, non-cirrhotic GT1b patients who were eligible for therapy with IFN and had a high viral load, defined as an HCV RNA level = 100,000 IU/mL and received at least one dose of the double-blind, active study drug.

In sub-study 2, 42 GT1b treatment-naïve and IFN (with or without RBV) treatment-experienced patients with compensated cirrhosis received open-label treatment for 12 weeks (Arm C) with SVR₁₂ and assessed as a secondary efficacy endpoint.

One patient from each arm (n=3/363) experienced on-treatment virologic failure [Arm A, 0.5% (n=1/215); Arm B, 0.9% (n=1/106); Arm C, 2.4% (n=1/42)]. Across all arms, eight patients (n=8/354) experienced post-treatment relapse [Arm A, 2.4% (n=5/209); Arm B, 1.0% (n=1/105); Arm C, 5.0% (n=2/40)].

AbbVie studied its two direct-acting antiviral treatment regimen without RBV in Japan due to patient and viral characteristics specific to the Japanese population, including high prevalence of GT1b.

About VIEKIRAX in Japan

Indication in Japan

VIEKIRAX is indicated for the improvement of viremia in chronic hepatitis C or compensated hepatic cirrhosis C in patients of serogroup 1 (genotype 1).

Summary of Safety Information

Contraindications

VIEKIRAX is contraindicated in patients with a history of known hypersensitivity to an ingredient in VIEKIRAX, patients with severe hepatic impairment (Child-Pugh C) or patients being treated with the following drugs: azelnidipine, triazolam, iv midazolam, blonanserin, pimozide, ergotamine tartrate, dihydroergotamine mesilate, ergometrine maleate, methylergometrine maleate, sildenafil citrate [Revatio], tadalafil [Adcirca], rivaroxaban, vardenafil hydrochloride hydrate, riociguat, simvastatin, atorvastatin calcium hydrate, carbamazepine, phenytoin, phenobarbital, rifampin, efavirenz, foods containing St. John’s Wort (Hypericum perforatum), ethinyl estradiol-containing medicinal products.

Precautions for Use

Positive result for HCV RNA should be confirmed before administering VIEKIRAX and decompensated cirrhosis should be excluded.

When VIEKIRAX is used for patients co-infected with HIV/HCV, administer VIEKIRAX only to patients whose virological suppression has been achieved by anti-HIV therapy as ritonavir may cause resistance against a HIV protease inhibitor.

During the administration of VIEKIRAX, perform liver function tests regularly because hepatic function disorder may occur.

Co-administration of VIEKIRAX with drugs that are substrates of CYP3A4, P-gp, BCRP, OATP1B1 or OATP1B3 may result in increased plasma concentrations of such drugs, potentially requiring dose adjustment or clinical monitoring

The safety of VIEKIRAX in pregnant women has not been established. VIEKIRAX should be used in pregnant women and women who may possibly be pregnant only if the expected therapeutic benefits outweigh the possible risks associated with treatment.

Do not administer VIEKIRAX to nursing mothers. If VIEKIRAX is administered to a nursing mother by necessity, breast feeding must be discontinued during treatment.

Safety and effectiveness have not been established in children.

Adverse Reactions

Major adverse reactions included peripheral edema in 15 subjects (4.1%), headache in 12 subjects (3.3%) and nausea in 10 subjects (2.8%)

About Enanta

Enanta Pharmaceuticals is a research and development-focused biotechnology company that uses its robust chemistry-driven approach and drug discovery capabilities to create small molecule drugs for viral infections and liver diseases. Enanta has developed novel protease and NS5A inhibitors that are members of the direct-acting-antiviral (DAA) inhibitor classes designed for use against the hepatitis C virus (HCV). Enanta’s protease inhibitors partnered with AbbVie include paritaprevir, which is contained in AbbVie’s marketed DAA regimens for HCV, and ABT-493, Enanta’s next generation protease inhibitor completing phase 2 development. Enanta also has a program to develop a host-targeted antiviral (HTA) inhibitor class for HCV targeted against cyclophilin, as well as another DAA program to develop nucleotide polymerase inhibitors. In addition, Enanta has other preclinical programs, including one in non-alcoholic steatohepatitis, or NASH, which is a condition that results in liver inflammation and liver damage caused by a buildup of fat in the liver.

Forward Looking Statements Disclaimer

This press release contains forward-looking statements, including with respect to the prospects for AbbVie’s VIEKIRAX and the expected timing of price reimbursement approval in Japan and the related milestone payment to Enanta. Statements that are not historical facts are based on our management’s current expectations, estimates, forecasts and projections about our business and the industry in which we operate and our management’s beliefs and assumptions. The statements contained in this release are not guarantees of future performance and involve certain risks, uncertainties and assumptions, which are difficult to predict. Therefore, actual outcomes and results may differ materially from what is expressed in such forward-looking statements. Important factors that may affect actual results include the efforts of AbbVie (our collaborator on paritaprevir) regarding price reimbursement approval and commercialization of VIEKIRAX in Japan; the level of market acceptance and the pricing and rate of reimbursement in Japan for VIEKIRAX and for competitive treatment regimens; the impact of competitive products on the use and sales of VIEKIRAX in Japan; and other risk factors described or referred to in “Risk Factors” in Enanta’s most recent Form 10-K for the fiscal year ended September 30, 2014 and other periodic reports filed more recently with the United States Securities and Exchange Commission. Enanta cautions investors not to place undue reliance on the forward-looking statements contained in this release. These statements speak only as of the date of this release, and Enanta undertakes no obligation to update or revise these statements, except as may be required by law.

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¹ VIEKIRAX [package insert]. Tokyo, Japan: AbbVie Ltd; 2015.

² Kohnodai Hospital. National Center for Global Health and Medicine [cited 20 February 2013]. Available from:http://www.ncgm.go.jp/center/forpatient_hcv.html

³ Gower, E. Global epidemiology and genotype distribution of the hepatitis C virus infection. Journal of Hepatology 2014; 61: S45-S57, Table 2.

⁴ Hajarizadeh B et al. Nat Rev Gastroenterol Hepatol 2013; 10: 553-562. Available from: http://www.nature.com/nrgastro/journal/v10/n9/fig_tab/nrgastro.2013.107_F1.html

⁵ Kumada H, et al. Randomized phase 3 trial of ombitasvir/paritaprevir/ritonavir for hepatitis C virus genotype 1b-infected Japanese patients with or without cirrhosis. Hepatology. 2015 Jul 3. doi: 10.1002/hep.27972.