Enanta Pharmaceuticals, Inc. Announces CHMP Positive Opinion For AbbVie’s VIEKIRAX + EXVIERA® Without Ribavirin For The Treatment Of Chronic Hepatitis C In Genotype 1b Patients With Compensated Cirrhosis

• EU label expansion supported by high cure rates shown in AbbVie’s TURQUOISE-III study, a dedicated Phase 3b study of VIEKIRAX + EXVIERA without ribavirin for 12 weeks
• 100 percent SVR12 (n=60/60) achieved in genotype 1b patients with compensated cirrhosis (Child-Pugh A); no patients discontinued treatment due to adverse events

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, announced today that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has granted a positive opinion for the use of VIEKIRAX^® (ombitasvir/paritaprevir/ritonavir tablets) + EXVIERA^® (dasabuvir tablets) without ribavirin (RBV) in chronic hepatitis C virus (HCV) infected genotype 1b (GT1b) patients with compensated cirrhosis (Child-Pugh A).

Paritaprevir is Enanta’s lead protease inhibitor identified within the ongoing Enanta-AbbVie collaboration and is one of the direct-acting antivirals in AbbVie’s VIEKIRAX + EXVIERA treatment regimen for chronic hepatitis C virus (HCV).

Approximately 160 million people worldwide are infected with HCV.¹ Genotype 1 is the most common type of HCV genotype, accounting for 60 percent of cases worldwide.² In the European Union, the most prevalent sub-genotype is 1b, accounting for 47 percent of the estimated nine million Europeans infected with chronic HCV. ^3,4

The CHMP opinion regarding the pending application for expansion of the label for VIEKIRAX + EXVIERA is supported by data from AbbVie’s Phase 3b TURQUOISE-III study, which is part of AbbVie’s larger clinical program investigating efficacy and safety in a broad range of GT1 patients. The Phase 3b TURQUOISE-III study is a dedicated Phase 3 study of VIEKIRAX + EXVIERA without RBV for 12 weeks in GT1b patients with compensated cirrhosis. Results from the TURQUOISE-III study showed 100 percent (n=60/60) of GT1b chronic HCV infected patients with compensated cirrhosis (Child-Pugh A) achieved sustained virologic response at 12 weeks post-treatment (SVR12) with VIEKIRAX + EXVIERA without RBV for 12 weeks. No patients discontinued treatment due to adverse events. The most commonly reported adverse events (>10 percent) were fatigue (22 percent), diarrhea (20 percent) and headache (18 percent).⁵

On January 7, AbbVie announced that its supplemental New Drug Application (sNDA) for a similar label expansion for VIEKIRA PAK^® in the U.S. was accepted and granted priority review by the U.S. Food and Drug Administration (FDA).

About VIEKIRAX^® + EXVIERA^® in the EU
VIEKIRAX + EXVIERA is approved in the European Union for the treatment of genotype 1 (GT1) chronic hepatitis C virus (HCV) infection, including patients with compensated cirrhosis (Child-Pugh A). VIEKIRAX is approved in the European Union for the treatment of genotype 4 (GT4) chronic HCV infection.

VIEKIRAX tablets consist of the fixed-dose combination of paritaprevir 150mg (NS3/4A protease inhibitor) and ritonavir 100mg with ombitasvir 25mg (NS5A inhibitor), dosed once daily. EXVIERA tablets consist of dasabuvir 250mg (non-nucleoside NS5B polymerase inhibitor) dosed twice daily. VIEKIRAX + EXVIERA are taken with or without ribavirin (RBV), dosed twice daily based on patient type. VIEKIRAX + EXVIERA is taken for 12 weeks with or without RBV, except in genotype 1a and GT4 patients with compensated cirrhosis, who should take it for 24 weeks with RBV.

EU Indications
VIEKIRAX is indicated in combination with other medicinal products for the treatment of chronic hepatitis C (CHC) in adults. EXVIERA is indicated in combination with other medicinal products for the treatment of CHC in adults.

Important EU Safety Information
Contraindications:
VIEKIRAX + EXVIERA are contraindicated in patients with severe hepatic impairment (Child-Pugh C). Patients taking ethinyl estradiol-containing medicinal products must discontinue them and switch to an alternative method of contraception prior to initiating VIEKIRAX + EXVIERA. Do not give VIEKIRAX with certain drugs that are sensitive CYP3A substrates or strong inhibitors of CYP3A. Do not give VIEKIRAX and EXVIERA with strong or moderate enzyme inducers. Do not give EXVIERA with certain drugs that are strong inhibitors of CYP2C8.

Special warnings and precautions for use:
VIEKIRAX and EXVIERA are not recommended as monotherapy and should be used in combination with other medicinal products for the treatment of hepatitis C infection.

Risk of Hepatic Decompensation and Hepatic Failure in Patients with Cirrhosis

Viekirax and Exviera are not recommended in patients with moderate hepatic impairment (Child-Pugh B). Patients with cirrhosis should be monitored for signs and symptoms of hepatic decompensation, including hepatic laboratory testing at baseline and during treatment.

ALT elevations
Transient elevations of ALT to >5x ULN without concomitant elevations of bilirubin occurred in clinical trials with VIEKIRAX + EXVIERA and were more frequent in a subgroup who were using ethinyl estradiol-containing contraceptives.

Pregnancy and concomitant use with ribavirin
Extreme caution must be taken to avoid pregnancy in female patients and female partners of male patients when VIEKIRAX with or without EXVIERA is taken in combination with ribavirin, see section 4.6 and refer to the Summary of Product Characteristics for ribavirin for additional information.

Use with concomitant medicinal products
Use caution when administering VIEKIRAX with fluticasone or other glucocorticoids that are metabolized by CYP3A4. A reduction in colchicine dosage or interruption in colchicine is recommended in patients with normal renal or hepatic function. VIEKIRAX with or without EXVIERA is expected to increase exposure of statins so certain statins need to be discontinued or dosages reduced. Low dose ritonavir, which is part of VIEKIRAX, may select for PI resistance in HIV co-infected patients without ongoing antiretroviral therapy. HIV co-infected patients without suppressive antiretroviral therapy should not be treated with VIEKIRAX.

Adverse Reactions
Most common (>20 percent) adverse reactions for VIEKIRAX + EXVIERA with RBV were fatigue and nausea.

Full summary of product characteristics is available at www.ema.europa.eu.

Globally, prescribing information varies; refer to the individual country product label for complete information.

About VIEKIRA PAK

USE

VIEKIRA PAK^® (ombitasvir, paritaprevir, and ritonavir tablets; dasabuvir tablets) is a prescription medicine used with or without ribavirin to treat adults with genotype 1 chronic (lasting a long time) hepatitis C (hep C) virus infection, including people who have a certain type of cirrhosis (compensated).

VIEKIRA is not for people with advanced cirrhosis (decompensated). If people have cirrhosis, they should talk to a healthcare provider before taking VIEKIRA.

IMPORTANT SAFETY INFORMATION

When taking VIEKIRA PAK in combination with ribavirin, people should read the Medication Guide that comes with ribavirin, especially the important pregnancy information.

What is the most important information to know about VIEKIRA PAK?

• VIEKIRA PAK may cause severe liver problems, especially in people with certain types of cirrhosis. These severe liver problems can lead to the need for a liver transplant, or can lead to death.
• VIEKIRA PAK can cause increases in liver function blood test results, especially if people use ethinyl estradiol-containing medicines (such as some birth control products).
  • Ethinyl estradiol-containing medicines (combination birth control pills or patches, such as Lo Loestrin^® FE, Norinyl^®, Ortho Tri-Cyclen Lo^®, Ortho Evra^®; hormonal vaginal rings such as NuvaRing^®; and the hormone replacement therapy medicine, Fem HRT^®) must be stopped before starting treatment with VIEKIRA PAK. If these medicines are used as a method of birth control, another method must be used during treatment with VIEKIRA PAK, and for about 2 weeks after treatment with VIEKIRA PAK ends. A doctor can provide instruction on when to begin taking ethinyl estradiol-containing medicines.
• A doctor should do blood tests to check liver function during the first 4 weeks of treatment and then as needed.
• A doctor may tell people to stop taking VIEKIRA PAK if signs or symptoms of liver problems develop. A doctor must be notified right away if any of the following symptoms develop or if they worsen during treatment with VIEKIRA PAK: tiredness, weakness, loss of appetite, nausea, vomiting, yellowing of the skin or eyes, color changes in stools, confusion, or swelling of the stomach area.

VIEKIRA PAK must not be taken if people:

• have certain liver problems
• take any of the following medicines: alfuzosin hydrochloride (Uroxatral^®) • carbamazepine (Carbatrol^®, Epitol^®, Equetro^®, Tegretol^®) • colchicine (Colcrys^®) • efavirenz (Sustiva^®, Atripla^®) • ergot containing medicines, including ergotamine tartrate (Cafergot^®, Migergot^®, Ergomar^®, Ergostat^®, Medihaler^®, Wigraine^®, Wigrettes^®), dihydroergotamine mesylate (D.H.E. 45^®, Migranal^®), methylergonovine (Ergotrate^®, Methergine^®) • ethinyl estradiol-containing medicines • gemfibrozil (Lopid^®) • lovastatin (Advicor^®, Altoprev^®, Mevacor^®) • midazolam (when taken by mouth) • phenytoin (Dilantin^®, Phenytek^®) • phenobarbital (Luminal^®) • pimozide (Orap^®) • rifampin (Rifadin^®, Rifamate^®, Rifater^®, Rimactane^®) • sildenafil citrate (Revatio^®), when taken for pulmonary artery hypertension (PAH) • simvastatin (Zocor^®, Vytorin^®, Simcor^®) • St. John’s wort (Hypericum perforatum) or a product that contains St. John’s wort • triazolam (Halcion^®)
• have had a severe skin rash after taking ritonavir (Norvir^®)

What should people tell a doctor before taking VIEKIRA PAK?

• If they have: liver problems other than hep C infection, HIV infection, or any other medical conditions.
• If they have had a liver transplant. If they take the medicines tacrolimus (Prograf^®) or cyclosporine (Gengraf^®, Neoral^®, Sandimmune^®), a doctor should check blood levels and, if needed, may change the dose of these medicines or how often they are taken, both during and after treatment with VIEKIRA PAK.
• If they are pregnant or plan to become pregnant or if they are breastfeeding or plan to breastfeed. It is not known if VIEKIRA PAK will harm a person’s unborn baby or pass into breast milk. A doctor should be consulted about the best way to feed a baby if taking VIEKIRA PAK. Pregnant females who have both hep C and HIV infection should talk with a doctor about enrolling in the antiretroviral pregnancy registry.
• About all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Some medicines interact with VIEKIRA PAK.
  • A new medicine must not be started without telling a doctor. A doctor will provide instruction on whether it is safe to take VIEKIRA PAK with other medicines.
  • When VIEKIRA PAK is finished, a doctor should be consulted on what to do if one of the usual medicines taken was stopped or if the dose changed during VIEKIRA PAK treatment.

What are the common side effects of VIEKIRA PAK?

• For VIEKIRA PAK used with ribavirin, side effects include tiredness, nausea, itching, skin reactions such as redness or rash, sleep problems, and feeling weak.
• For VIEKIRA PAK used without ribavirin, side effects include nausea, itching, and sleep problems.

These are not all of the possible side effects of VIEKIRA PAK. A doctor should be notified if there is any side effect that is bothersome or that does not go away.

This is the most important information to know about VIEKIRA PAK. For more information, talk with a doctor.

People are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

Click here for full Prescribing Information, including the Medication Guide.

If people cannot afford their medication, they should contact www.pparx.org for assistance.

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’s research and development is currently focused on four disease targets: Hepatitis C Virus (HCV), Hepatitis B Virus (HBV), Non-alcoholic Steatohepatitis (NASH) and Respiratory Syncytial Virus (RSV).

Enanta has developed novel protease inhibitors 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, developed through its collaboration with AbbVie, include paritaprevir, which is contained in AbbVie’s marketed DAA regimens for HCV, and ABT-493, Enanta’s next-generation protease inhibitor, which AbbVie is developing in phase 3 studies in combination with ABT-530, AbbVie’s next-generation NS5A inhibitor. Enanta has also discovered a cyclophilin inhibitor, EDP-494, a novel host-targeting mechanism for HCV, which is now in a phase 1 clinical development, and EDP-305, an FXR agonist, which Enanta plans to advance into clinical development for NASH later in 2016. Please visit www.enanta.com for more information on our programs and pipeline.

Forward Looking Statements Disclaimer
This press release contains forward-looking statements, including statements with respect to the prospects for EMA approval of the label expansion for VIEKIRAX + EXVIERA. Statements that are not historical facts are based on management’s current expectations, estimates, forecasts and projections about Enanta’s business and the industry in which it operates and 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 and risks that may affect actual results include: the efforts of AbbVie (our collaborator on paritaprevir that is marketing VIEKIRAX) to obtain regulatory approval of the label expansion for VIEKIRAX; the development, regulatory and marketing efforts of others with respect to competitive HCV treatment regimens; regulatory and reimbursement actions affecting VIEKIRAX, any competitive regimen, or both; 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, 2015 and any other periodic reports filed more recently with the 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 Lavanchy D. Evolving epidemiology of hepatitis C virus. Clin Microbiol Infect. 2011; 17(2):107-15

² Global Alert and Response (GAR): Hepatitis C. World Health Organisation Web site. http://www.who.int/csr/disease/hepatitis/hepc.pdf. Published 2003. Accessed February, 2016.

³ O'Leary JG, Davis GL. Hepatitis C. In: Feldman M, Friedman LS, Brandt LJ, eds. Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/Management. 9th ed, Vol 1. Philadelphia, PA: Saunders Elsevier. 2010:1313-1335

⁴ Hatzakis, A. et. al. The state of hepatitis B and C in Europe: report from the hepatitis B and C summit conference. Journal of Viral Hepatitis, 2011; 18 (Suppl. 1): 1-16

⁵ Feld JJ, Moreno C, Trinh R, et al. Sustained virologic response of 100% in HCV genotype 1b patients with cirrhosis receiving ombitasvir/paritaprevir/r and dasabuvir for 12 weeks. J Hepatol. 2016 Feb;64(2):301-7