Paritaprevir (ABT-450)/ombitasvir/dasabuvir- List Of Upcoming and Recruiting Clinical Trials

Paritaprevir (ABT-450)/ombitasvir/dasabuvir- List Of Upcoming and Recruiting Clinical Trials

Provided below is a list of verified clinical trials using AbbVie's three direct-acting antiviral oral free regimen or "3-DAA combination" consisting of boosted protease inhibitor paritaprevir (also known as ABT-450/r ), NS5A inhibitor ombitasvir (ABT-267), non-nucleoside polymerase inhibitor dasabuvir (ABT-333) with and without ribavirin for the treatment of hepatitis C, and Type 1 (HIV-1) co-infection. Trial participants will represent different stages of disease and genotype. A bit of background information on AbbVie's 3-DAA combination is included as well.

Clinical trials on this page are not a complete list; to learn more about HCV trials or to find out if a study is enrolling patients in your area, please click here. View additional hepatitis trials updated in the last 30 days @ ClinicalTrials.gov

Updates
In June 2014, the U.S. FDA Granted Priority Review to AbbVie for Investigational, All-Oral, Interferon-Free Therapy for the Treatment of Genotype 1 Chronic Hepatitis C.

NORTH CHICAGO, Ill., June 13, 2014 /PRNewswire/ -- AbbVie (NYSE: ABBV) announced today that the New Drug Application (NDA) for its investigational, all-oral, interferon-free regimen for the treatment of adult patients with chronic genotype 1 (GT1) hepatitis C virus (HCV) infection has been accepted by the U.S. Food and Drug Administration (FDA) and has been granted priority review. 

The NDA was submitted on April 21, 2014 and is supported by data from a large clinical program including six Phase III studies of more than 2,300 GT1 patients in over 25 countries. The regimen was granted a Breakthrough Therapy designation by the FDA in May 2013, a status given to investigational treatments for serious or life-threatening conditions with preliminary clinical evidence demonstrating substantial improvement on at least one clinically significant endpoint compared to available therapy.

In addition, accelerated assessment was granted a few days later by the European Medicines Agency (EMA) 

Accelerated assessment, which is designated to new medicines of major public health interest, was granted by the EMA for AbbVie's investigational HCV regimen in May. Validation of the MAAs confirms that the submissions are complete and starts the EMA's centralized review process. If approved, AbbVie's regimen could be available for marketing in the European Union (EU) in the first quarter of 2015.

August

Paritaprevir (ABT-450/ritonavir)/ombitasvir/dasabuvir with and without ribavirin

Interferon-free regimens yield 96%-100% SVRs
By: MARY ANN MOON
The primary efficacy endpoint – a sustained virologic response (SVR) rate noninferior to the historical rate for interferon-containing regimens in comparable patients – was met and surpassed: 96.6% for ABT-450/ritonavir/ombitasvir/dasabuvir plus ribavirin and 100% for ABT-450/ritonavir/ombitasvir/dasabuvir without ribavirin.

Full Article; GI & Hepatology News Digital Network

Dr. Pietro Andreone discusses his manuscript "ABT-450, Ritonavir, Ombitasvir, and Dasabuvir Achieves 97% and 100% Sustained Virologic Response With or Without Ribavirin in Treatment-Experienced Patients With HCV Genotype 1b Infection."

 

April - May 2014
VIDEO – ‘Three D’ for hepatitis C called ‘revolutionary’
Dr. Bruce R. Bacon called this oral regimen "revolutionary" Hear his thoughts on treatment with ABT-450 with ritonavir, ombitasvir, and dasabuvir (known as the "three D" regimen) with or without ribavirin. 

New England Journal of Medicine
Retreatment of HCV with ABT-450/r–Ombitasvir and Dasabuvir with Ribavirin
In this phase 3 trial we evaluated the efficacy and safety of the interferon-free combination of ABT-450 with ritonavir (ABT-450/r), ombitasvir (also known as ABT-267), dasabuvir (also known as ABT-333), and ribavirin for the retreatment of HCV in patients who were previously treated with peginterferon–ribavirin.

New England Journal of Medicine: With Cirrhosis
ABT-450/r–Ombitasvir and Dasabuvir with Ribavirin for Hepatitis C with Cirrhosis
Interferon-containing regimens for the treatment of hepatitis C virus (HCV) infection are associated with increased toxic effects in patients who also have cirrhosis. We evaluated the interferon-free combination of the protease inhibitor ABT-450 with ritonavir (ABT-450/r), the NS5A inhibitor ombitasvir (ABT-267), the nonnucleoside polymerase inhibitor dasabuvir (ABT-333), and ribavirin in an open-label phase 3 trial involving previously untreated and previously treated adults with HCV genotype 1 infection and compensated cirrhosis.

New England Journal of Medicine: No Cirrhosis
Treatment of HCV with ABT-450/r–Ombitasvir and Dasabuvir with Ribavirin
The interferon-free combination of the protease inhibitor ABT-450 with ritonavir (ABT-450/r) and the NS5A inhibitor ombitasvir (also known as ABT-267) plus the nonnucleoside polymerase inhibitor dasabuvir (also known as ABT-333) and ribavirin has shown efficacy against the hepatitis C virus (HCV) in patients with HCV genotype 1 infection. In this phase 3 trial, we evaluated this regimen in previously untreated patients with HCV genotype 1 infection and no cirrhosis.

Coverage@NATAP
Slides
EASL: SAPPHIRE-II: PHASE 3 PLACEBO-CONTROLLED STUDY OF INTERFERON-FREE, 12-WEEK REGIMEN OF ABT-450/r/ABT-267, ABT-333, AND RIBAVIRIN IN 394 TREATMENT-EXPERIENCED ADULTS WITH HEPATITIS C VIRUS GENOTYPE 

Recruiting 

Recruiting

Locations  United States 28 Study Locations 3 in Puerto Rico

A Study to Evaluate the Safety and Efficacy of ABT-450/Ritonavir/ABT-267 (ABT-450/r/ABT-267) and ABT-333 Coadministered With Ribavirin (RBV) in Adults With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection and Human Immunodeficiency Virus, Type 1 (HIV-1) Coinfection 

ClinicalTrials.gov Identifier: NCT01939197

Conditions: Hepatitis C Virus Infection; Human Immunodeficiency Virus Infection; Chronic Hepatitis C; Compensated Cirrhosis and Non-cirrhotics

Interventions: Drug: ABT-450/r/ABT-267; Drug: ABT-333; Drug: Ribavirin (RBV)

Contact: Melanie Gloria, BS 847-936-0714 melanie.gloria@abbvie.com

Contact: Karmin Robinson-Morgan, BS 847-935-5421 karmin.y.robinson@abbvie.com

Recruiting - Some locations Active and not recruiting

Locations  United States, Australia, France, Germany, Spain, United Kingdom

A Study to Evaluate Long-term Outcomes Following Treatment With ABT-450/Ritonavir/ABT-267 (ABT-450/r/ABT-267) and ABT-333 With or Without Ribavirin (RBV) in Adults With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection
ClinicalTrials.gov Identifier: NCT02167945

Condition: Chronic Hepatitis C Virus (HCV) Infection Genotype 1

Interventions: Drug: ABT-450/r/ABT-267; Drug: ABT-333; Drug: Ribavirin (RBV)

Contact: Sundeep K Grewal, BS 847-937-3249 sundeep.grewal@abbvie.com

Contact: George S LIOSSIS 847-937-6450 george.liossis@abbvie.com

Recruiting - Most Study Locations Recruiting 

135 Study Locations United States, Australia, Belgium, Canada, Denmark, Germany, Ireland, Netherlands, New Zealand, Puerto Rico, Spain, United Kingdom

A Follow up Study Designed to Obtain Long Term Data on Subjects Who Either Achieved a Sustained Virologic Response or or Did Not Achieve a Sustained Virologic Response in an Abbott Sponsored Hepatitis C Study 

ClinicalTrials.gov Identifier: NCT01773070

Condition: Hepatitis C

Interventions: Drug: ABT-450/ritonavir; Drug: ABT-333; Drug: ABT-267

Contact: Rebecca Craft, BS1-901-854-2643 rebecca.craft@abbvie.com

Contact: Lia Hunter, PhD+44 (0)208 761 7684 lia.hunter@abbvie.com

Recruiting - Some locations Active and not recruiting

Locations  United States, Australia, France, Germany, Spain, United Kingdom

A Study to Evaluate Chronic Hepatitis C Infection in Adult Liver Transplant Recipients

ClinicalTrials.gov Identifier: NCT01782495

Condition: Chronic Hepatitis C Infection

Interventions: Drug: ABT-450/r/ABT-267; Drug: ABT-333; Drug: ribavirin (RBV)
Contact: Elizabeth Colon, BA 847-938-4572 elizabeth.colon@abbvie.com
Contact: Melissa Cook, MS 847-937-1399 melissa.cook@abbvie.com

Recruiting

Locations United States

A Study to Evaluate the Safety and Antiviral Effect of ABT-450/Ritonavir and ABT-530 Coadministered With and Without Ribavirin in Adults With Genotype 3 Hepatitis C (HCV) Infection

ClinicalTrials.gov Identifier: NCT02068222

Condition: Chronic Hepatitis C Infection

Interventions: Drug: ABT-450/r Drug: ABT-530 Drug: Ribavirin (RBV)
Contact: Charles E Meyer, BS (847) 938-6564 charles.e.meyer@abbvie.com

Contact: Traci Baker, MS (847) 936-6555 traci.baker@abbvie.com

Not yet recruiting 

A Study to Evaluate the Safety and Efficacy of ABT-450/Ritonavir/ABT-267 and ABT-333 With Ribavirin in Adults With Genotype 1 Chronic Hepatitis C Virus Infection and Decompensated Cirrhosis

‎Friday, ‎August ‎15, ‎2014, ‏‎12:00:00 PM 

ClinicalTrials.gov Identifier: NCT02219477

Conditions: Chronic Hepatitis C; Decompensated Cirrhosis; Hepatitis C Virus

Interventions: Drug: ABT-450/ritonavir/ABT-267; Drug: ABT-333; Drug: Ribavirin
Sponsor: AbbVie
Not yet recruiting - verified August 2014

A Study to Evaluate the Safety and Efficacy of Ombitasvir/ABT-450/Ritonavir and Dasabuvir in Adults With Genotype 1b Chronic Hepatitis C Virus (HCV) Infection and Cirrhosis
‎Friday, ‎August ‎15, ‎2014, ‏‎12:00:00 PM

ClinicalTrials.gov Identifier: NCT02219503

Conditions: Chronic Hepatitis C Infection; Compensated Cirrhosis; Hepatitis C Virus

Interventions: Drug: ombitasvir/ABT-450/ritonavir; Drug: dasabuvir
Sponsor: AbbVie
Not yet recruiting - verified August 2014

A Study to Evaluate Long-term Outcomes Following Treatment With ABT-450/Ritonavir/ABT-267 (ABT-450/r/ABT-267) and ABT-333 With or Without Ribavirin (RBV) in Adults With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection
‎Friday, ‎August ‎15, ‎2014, ‏‎12:00:00 PM
ClinicalTrials.gov Identifier: NCT02219490

Condition: Chronic Hepatitis C Virus (HCV) Infection Genotype 1
Interventions: Drug: ABT-450/r/ABT-267; Drug: ABT-333; Drug: Ribavirin (RBV)
Sponsor: AbbVie
Not yet recruiting - verified August 2014

A Study to Evaluate Chronic Hepatitis C Infection in Cirrhotic Adults With Genotype 1b Infection
‎Tuesday, ‎August ‎12, ‎2014, ‏‎12:00:00 PM 

ClinicalTrials.gov Identifier: NCT02216422

Condition: Chronic Hepatitis C Infection
Interventions: Drug: ABT-450/r/ABT-267; Drug: ABT-333; Drug: Ribavirin (RBV)
Sponsor: AbbVie
Not yet recruiting - verified August 2014

Ombitasvir/ABT-450/Ritonavir and Dasabuvir With or Without Ribavirin in Treatment-Naïve HCV Genotype 1-Infected Adults With Chronic Kidney Disease
‎Thursday, ‎July ‎31, ‎2014, ‏‎12:00:00 PM 

ClinicalTrials.gov Identifier: NCT02207088

Conditions: Chronic Hepatitis C; Hepatitis C Virus; Compensated Cirrhosis; Severe Renal Impairment; End-stage Renal Disease
Interventions: Drug: ombitasvir/ABT-450/ritonavir; Drug: dasabuvir; Drug: Ribavirin
Sponsor: AbbVie
Not yet recruiting - verified July 2014

For additional information visit HCV Advocate News and Pipeline for trial updates;

AbbVie
Bristol-Myers Squibb (BMS)
Gilead
Merck
Tibotec / Janssen
Vertex
**Quick Reference Guide*

AbbVie, Enanta’s collaboration partner for ABT-450, has submitted (NDA) to the FDA for interferon-free regimen

Investment Commentary

AbbVie heads to the FDA with its hep C combo in a race with Gilead, Merck
April 22, 2014 | By Damian Garde 

AbbVie ($ABBV) has submitted an FDA application for its promising all-oral hepatitis C treatment, expecting approval this year as it prepares for a three-way race with perceived leaders Gilead Sciences ($GILD) and Merck ($MRK).......

Press Release

Enanta Pharmaceuticals Announces New Drug Application Submission to the U.S. FDA for All-Oral, Interferon-Free Hepatitis C 

Regimen Filing Triggers Milestone Payment to Enanta

AbbVie’s submission to FDA triggers $20 million milestone payment to Enanta

Regimen includes Enanta’s and AbbVie’s protease inhibitor ABT-450 

April 22, 2014 08:53 AM Eastern Daylight Time

WATERTOWN, Mass.--(BUSINESS WIRE)--Enanta Pharmaceuticals, Inc. (NASDAQ:ENTA), a research and development-focused biotechnology company dedicated to creating small molecule drugs in the infectious disease field, today announced that AbbVie, Enanta’s collaboration partner for ABT-450, has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) seeking approval for an investigational, all-oral, interferon-free regimen for the treatment of adult patients with chronic genotype 1 (GT1) hepatitis C virus (HCV) infection.

“No all-oral therapy has yet been approved to treat GT1 HCV infection, which is estimated to affect approximately 70% of the 3.2 million people of the U.S. population infected with HCV.”

The three direct-acting antiviral regimen consists of boosted protease inhibitor ABT-450/ritonavir, NS5A inhibitor ABT-267, and non-nucleoside polymerase inhibitor ABT-333. ABT-450 is the lead protease inhibitor developed through Enanta’s collaboration with AbbVie.

The U.S. NDA filing triggers a $20 million milestone payment to Enanta from AbbVie. AbbVie also plans to submit applications for regulatory approval of its regimen in the European Union in early May. Enanta is entitled to receive an additional $20 million upon the first regulatory filing in the European Union for a regimen containing a collaboration compound.

The NDA is supported by AbbVie’s data from the largest all-oral, interferon-free clinical program in GT1 patients conducted to date,¹ with six phase 3 studies that included more than 2,300 patients in over 25 countries.

“This submission marks a very significant step toward Enanta being part of the first wave of all-oral therapies that may be approved to treat patients with genotype 1 hepatitis C virus,” stated Jay R. Luly, Ph.D., Enanta’s President and Chief Executive Officer. “No all-oral therapy has yet been approved to treat GT1 HCV infection, which is estimated to affect approximately 70% of the 3.2 million people of the U.S. population infected with HCV.”²

In May of 2013, AbbVie's investigational direct-acting antiviral (DAA) regimen with and without ribavirin for HCV genotype 1 was designated as a Breakthrough Therapy by the U.S. FDA. This designation is intended to help expedite the development of drugs for serious or life-threatening conditions and is based in part on preliminary clinical evidence demonstrating a drug or regimen may have substantial improvement on at least one clinically significant endpoint compared to available therapy. 

Protease Inhibitor Collaboration with AbbVie
In December 2006, Enanta and Abbott announced a worldwide agreement to collaborate on the discovery, development and commercialization of HCV NS3 and NS3/4A protease inhibitors and HCV protease inhibitor-containing drug combinations. ABT-450 is a protease inhibitor identified as a lead compound through the collaboration. Under the agreement, AbbVie is responsible for all development and commercialization activities for ABT-450. Enanta received $57 million in connection with signing the collaboration agreement, has received $55 million in subsequent clinical milestone payments, is entitled to receive $20 million in connection with the NDA filing in the U.S. described above, and is eligible to receive up to an additional $175 million in payments for regulatory and commercialization milestones, as well as double-digit royalties worldwide on any revenue allocable to the collaboration’s protease inhibitors. Also, for any additional collaborative HCV protease inhibitor product candidate developed under the agreement, Enanta holds an option to modify the U.S. portion of it rights to receive milestone payments and worldwide royalties. With this option, Enanta can fund 40 percent of U.S. development costs and U.S. commercialization efforts (sales and promotion costs) for the additional protease inhibitor in exchange for 40 percent of any U.S. profits ultimately achieved after regulatory approval, instead of receiving payments for U.S. commercial regulatory approval milestones and royalties on U.S. sales of that protease inhibitor. 

About ABT-450
ABT-450 is an NS3 protease inhibitor discovered through Enanta’s ongoing collaboration with AbbVie. AbbVie and Enanta have an agreement to collaborate on the discovery, development and commercialization of HCV NS3 and NS3/4A protease inhibitors. Protease inhibitors play an essential role in the viral life cycle of the hepatitis C virus (HCV). Inhibition of the protease prevents non-structural (NS) proteins from forming and thereby prevents replication and survival of the HCV virus. ABT-450 is part of AbbVie’s investigational regimen for HCV that consists of boosted protease inhibitor ABT-450/ritonavir (referred to as ABT-450/r), NS5A inhibitor ABT-267 and non-nucleoside polymerase inhibitor ABT-333. 

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 in the infectious disease field. Enanta is discovering, and in some cases developing, novel inhibitors designed for use against the hepatitis C virus (HCV). These inhibitors include members of the direct acting antiviral (DAA) inhibitor classes – protease (partnered with AbbVie), NS5A (partnered with Novartis) and nucleotide polymerase – as well as a host-targeted antiviral (HTA) inhibitor class targeted against cyclophilin. Additionally, Enanta has created a new class of antibiotics, called Bicyclolides, for the treatment of multi-drug resistant bacteria, with a focus on developing an intravenous and oral treatment for hospital and community MRSA (methicillin-resistant Staphylococcus aureus) infections.

Related
Retreatment of HCV with ABT-450/r–Ombitasvir and Dasabuvir with Ribavirin
A phase 2b study involving patients with HCV genotype 1 infection who had a null response to prior therapy with peginterferon–ribavirin showed that the rate of sustained virologic response to 12 weeks of treatment with ABT-450/r, ombitasvir, dasabuvir, and ribavirin was 93% 24 weeks after the end of treatment.14 We report the results of SAPPHIRE-II, an international, randomized, placebo-controlled, double-blind, phase 3 trial assessing the efficacy and safety of 12 weeks of the all-oral regimen of ABT-450/r–ombitasvir and dasabuvir with ribavirin in patients with HCV genotype 1 infection and no cirrhosis who had received previous treatment with peginterferon–ribavirin.

ABT-450/r–Ombitasvir and Dasabuvir with Ribavirin for Hepatitis C with Cirrhosis
Interferon-containing regimens for the treatment of hepatitis C virus (HCV) infection are associated with increased toxic effects in patients who also have cirrhosis. We evaluated the interferon-free combination of the protease inhibitor ABT-450 with ritonavir (ABT-450/r), the NS5A inhibitor ombitasvir (ABT-267), the nonnucleoside polymerase inhibitor dasabuvir (ABT-333), and ribavirin in an open-label phase 3 trial involving previously untreated and previously treated adults with HCV genotype 1 infection and compensated cirrhosis.

EASL- Antiviral Regimen for Hepatitis C with Cirrhosis

International Liver Congress 2014 
The New England Journal Of Medicine NEJM 

Original Article
Curing Chronic Hepatitis C: The Arc of a Medical Triumph 
Podcast -  Listen
Chronic hepatitis C is a major cause of liver cirrhosis and hepatocellular carcinoma worldwide. Some 130 million to 170 million people, or about 3% of the world's population, are chronically infected with the hepatitis C virus (HCV). In the United States, chronic hepatitis C, the most common cause of liver-related death and reason for liver transplantation, recently eclipsed human immunodeficiency virus (HIV) infection as a cause of death. The development of direct-acting antiviral agents (DAAs) has revolutionized HCV treatment by offering genuine prospects for the first comprehensive cure of a chronic viral infection in humans. This success can be traced to important scientific, clinical, and regulatory developments.. 

Treating Hepatitis C in Lower-Income Countries
Just two decades after the identification of hepatitis C virus (HCV), an improved understanding of the viral lifecycle has led to several new classes of highly promising therapies. By as early as 2015, sustained virologic response rates will be in the 90% range for most HCV genotypes, and this effective “cure” will be achieved through short, convenient courses of interferon-free, fixed-dose, single-pill regimens with adverse-effect profiles that are markedly better than those of past treatments. The use of these agents is expected to reduce the intensity of follow-up monitoring, the rate of hospitalizations for adverse effects, dependence on specialist care, and resource demands associated with disease progression, including those for liver transplantation and management of end-stage liver disease and liver cancer. However, with drug costs that may exceed $90,000 per course, it remains to be seen how these remarkable advances will extend to the estimated 150 million people with HCV infection living outside the target high-income markets for these agents...
  
Editorial
Therapy for Hepatitis C: The Costs of Success
Welcomed and exciting results from three large, controlled trials of different regimens of oral antiviral agents for chronic hepatitis C, genotype 1, have now been published in the Journal.1-3 The regimens all included the combination of ledipasvir and sofosbuvir, two new direct-acting antiviral agents with potent activity against hepatitis C virus (HCV). The two drugs were given as a single tablet once daily for 8, 12, or 24 weeks, with or without ribavirin. The results were consistent and striking: the various regimens yielded rates of sustained virologic response of 93% to 99%. The combination of ledipasvir and sofosbuvir alone (without ribavirin) for 12 weeks was associated with response rates of 94% in the ION-2 study and 99% in the ION-1 study.1,2 Extending therapy to 24 weeks increased the rate minimally (to 98% and 99%, respectively). In contrast, adding ribavirin provided no further benefit, regardless of duration. In previously untreated patients without cirrhosis, shortening the duration of therapy (without ribavirin) to 8 weeks did not lessen the rate of response (94%, vs. 95% with 12 weeks of therapy in the ION-1 study).3 Importantly, the single-tablet regimen was easy to administer and had few side effects; among the 539 patients who received ledipasvir and sofosbuvir alone for 12 weeks in these three trials, only 2 stopped therapy early because of adverse events....

Original Article
Retreatment of HCV with ABT-450/r–Ombitasvir and Dasabuvir with Ribavirin
In this phase 3 trial we evaluated the efficacy and safety of the interferon-free combination of ABT-450 with ritonavir (ABT-450/r), ombitasvir (also known as ABT-267), dasabuvir (also known as ABT-333), and ribavirin for the retreatment of HCV in patients who were previously treated with peginterferon–ribavirin. 

Without Cirrhosis
Treatment of HCV with ABT-450/r–Ombitasvir and Dasabuvir with Ribavirin  
The interferon-free combination of the protease inhibitor ABT-450 with ritonavir (ABT-450/r) and the NS5A inhibitor ombitasvir (also known as ABT-267) plus the nonnucleoside polymerase inhibitor dasabuvir (also known as ABT-333) and ribavirin has shown efficacy against the hepatitis C virus (HCV) in patients with HCV genotype 1 infection. In this phase 3 trial, we evaluated this regimen in previously untreated patients with HCV genotype 1 infection and no cirrhosis.

Antiviral Regimen for Hepatitis C with Cirrhosis
ABT-450/r–Ombitasvir and Dasabuvir with Ribavirin for Hepatitis C with Cirrhosis
Interferon-containing regimens for the treatment of hepatitis C virus (HCV) infection are associated with increased toxic effects in patients who also have cirrhosis. We evaluated the interferon-free combination of the protease inhibitor ABT-450 with ritonavir (ABT-450/r), the NS5A inhibitor ombitasvir (ABT-267), the nonnucleoside polymerase inhibitor dasabuvir (ABT-333), and ribavirin in an open-label phase 3 trial involving previously untreated and previously treated adults with HCV genotype 1 infection and compensated cirrhosis.

Without Cirrhosis
Ledipasvir and Sofosbuvir for 8 or 12 Weeks for Chronic HCV without Cirrhosis
High rates of sustained virologic response were observed among patients with hepatitis C virus (HCV) infection who received 12 weeks of treatment with the nucleotide polymerase inhibitor sofosbuvir combined with the NS5A inhibitor ledipasvir. This study examined 8 weeks of treatment with this regimen.

Original Article 
Ledipasvir and Sofosbuvir for Untreated HCV Genotype 1 Infection
In phase 2 studies, treatment with the all-oral combination of the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor ledipasvir resulted in high rates of sustained virologic response among previously untreated patients with hepatitis C virus (HCV) genotype 1 infection.

EASL AbbVie's ABT-450 - Cure Rate for Experimental Hepatitis C Drug Tops 95 Percent

New England Journal of Medicine:
Retreatment of HCV with ABT-450/r–Ombitasvir and Dasabuvir with Ribavirin
In this phase 3 trial we evaluated the efficacy and safety of the interferon-free combination of ABT-450 with ritonavir (ABT-450/r), ombitasvir (also known as ABT-267), dasabuvir (also known as ABT-333), and ribavirin for the retreatment of HCV in patients who were previously treated with peginterferon–ribavirin...

Coverage@ Healio
SAPPHIRE II: Ritonavir-boosted triple regimen plus ribavirin achieved high SVR12 rates.
LONDON — Sustained virologic response rates at 12 weeks were more than 90% across several treatment groups in a cohort of patients who previously failed pegylated interferon and ribavirin therapy who received ritonavir-boosted ABT-450, ABT-267 and ABT-333 with ribavirin....

Coverage@NATAP
Slides
EASL: SAPPHIRE-II: PHASE 3 PLACEBO-CONTROLLED STUDY OF INTERFERON-FREE, 12-WEEK REGIMEN OF ABT-450/r/ABT-267, ABT-333, AND RIBAVIRIN IN 394 TREATMENT-EXPERIENCED ADULTS WITH HEPATITIS C VIRUS GENOTYPE 1 
(04/10/14) 

Cure Rate for Experimental Hepatitis C Drug Tops 95 Percent
April 10
HealthDay New

Researchers report that an experimental drug has cured more than 95 percent of patients infected with hepatitis C, including some who failed other treatments.

If it wins approval from the U.S. Food and Drug Administration, this new drug, called ABT-450, could potentially compete with another innovative hepatitis C medication that costs $1,000 a day.

Nearly 3 million Americans have hepatitis C, a disease that can cause liver cirrhosis and cancer.

These newer, advanced treatments are better-tolerated and easier to take than interferon, the traditional standard treatment for hepatitis C, researchers say.

"Interferon is no longer required to cure hepatitis C," said Dr. Stefan Zeuzem, a professor of medicine at the J.W. Goethe University Hospital in Frankfurt, Germany, and lead researcher on the ABT-450 study.

His research pairing ABT-450 with other interferon-free medications showed "almost all patients with chronic hepatitis C can be cured even if previous treatments were unsuccessful," Zeuzem said.

The report was published online April 10 in the New England Journal of Medicine, to coincide with presentation of the findings at the annual meeting of the European Association for the Study of the Liver in London. The drug trial was funded by the drug's maker, AbbVie.

"Hepatitis C is a big, bad problem," said Dr. William Carey, a liver specialist at the Cleveland Clinic in Ohio.

This new drug represents "one among many breakthroughs in our ability to deal with hepatitis C," Carey said.

An advantage to this treatment is that it is a pill, while interferon is given in weekly injections. Also, older treatments went on for a year, while this new therapy takes only three months to work, Carey said.

Interferon treatment also has severe side effects, including fatigue and flu-like symptoms.

"This is not the only drug combination that is interferon-free, but it's a very promising one," he said.

One drawback to the therapy is that some pills are taken once a day and some twice, which might make following the treatment tricky. Carey hopes that treatment eventually is simplified. "Wouldn't it be great if we could take one or two pills once a day and be done with it?" he said.

Since many people with hepatitis C remain symptom-free, the medical community has not agreed on whom to treat.

With these new cures, that question becomes easier to answer, Carey said. "When you have a treatment that is this simple, effective and free of side effects, there are fewer and fewer reasons to think about withholding treatment," he noted.

"The major barrier is cost," he added.

Whether the new drug will be priced like Sovaldi, the $1,000-a-day medication, is still unknown.

With Sovaldi, the necessary three-month course costs $90,000, plus any other drug expenses and medical care.

Carey said some insurance companies cover the cost of the drug, while others have denied it.

Cost is even more significant in light of the millions of Baby Boomers who are five times more likely to be infected with hepatitis C than other adults, according to the U.S. Centers for Disease Control and Prevention.

"It's going to get harder as time goes on for insurance companies not to cover the cost of these drugs," Carey said. "This is a curable disease."

According to a CBS News report, lawmakers and insurance companies complain that Gilead Sciences, the maker of Sovaldi, is trying to "milk desperate patients." Gilead says that, despite the high price, Sovaldi is cheaper because it "cures patients quickly and eliminates a long and expensive treatment using other drugs."

For this phase 3 trial of ABT-450 -- typically the last trial needed for FDA approval -- nearly 400 patients were randomly assigned to take a placebo or a combination of ABT-450 and these other pills: ombitasvir, ritonavir, dasabuvir or ribavirin. All patients had been treated before, but saw their diseases return or had a poor response or no response to treatment.

Taking the ABT-450 combination, 96.3 percent of the patients responded, the researchers said.

Previous research showed that patients who had never been treated also responded to this combination.

Dr. Marc Siegel, an associate professor of medicine at NYU Langone Medical Center, New York City, said the results look promising for the millions of people with hepatitis C.

"Hepatitis C is under-diagnosed," said Siegel.

These new treatments, with their high cure rates, make it important to diagnose and treat hepatitis C early to prevent cirrhosis and liver cancer, he said.

Hepatitis C can be spread by injectable drug use or sexual contact with an infected person. The U.S. Centers for Disease Control and Prevention recommends one-time screening for those born between 1945 and 1965 -- that's potentially millions of people who would qualify for treatment.

More information
For more information on hepatitis C, visit the U.S. National Library of Medicine.

Posted: April 2014

Press Release

Enanta Pharmaceuticals Announces Detailed Data from SAPPHIRE-I and SAPPHIRE-II Phase 3 Studies in Patients with Chronic Hepatitis C Virus Being Presented at EASL 2014

April 11, 2014 

WATERTOWN, Mass. — Enanta Pharmaceuticals, Inc. (NASDAQ:ENTA), a research and development-focused biotechnology company dedicated to creating small molecule drugs in the infectious disease field, today announced that detailed results from AbbVie’s pivotal phase 3 SAPPHIRE-I study, will be presented today at the International Liver Congress (ILC), which is the 49th Annual Meeting of the European Association for the Study of the Liver (EASL) and featured in the ILC press conference. Results from the SAPPHIRE-II study were presented at the congress yesterday. Additionally, results from both the SAPPHIRE-I and SAPPHIRE-II studies have been published on-line in the New England Journal of Medicine.

The SAPPHIRE-I and SAPPHIRE-II studies report results from AbbVie’s investigational three direct-acting antiviral regimen containing ABT-450, Enanta’s lead protease inhibitor developed through Enanta’s collaboration with AbbVie. The regimen consists of boosted protease inhibitor ABT-450/ritonavir, NS5A inhibitor ABT-267, and non-nucleoside polymerase inhibitor ABT-333.
In the SAPPHIRE-I (N=631) and SAPPHIRE-II (N=394) placebo-controlled studies, adult, non-cirrhotic patients with chronic genotype 1 (GT1) hepatitis C virus (HCV) infection receiving the investigational three-direct-acting antiviral regimen with ribavirin (RBV) for 12 weeks achieved sustained virologic response rates 12 weeks post-treatment (SVR₁₂) of 96.2 percent (n=455/473) and 96.3 percent (n=286/297), respectively.

In SAPPHIRE-II, treatment-experienced sub-populations randomized to the three direct-acting antiviral regimen with RBV in the study were prior null responders (49.2 percent), prior relapsers (29.0 percent) and prior partial responders (21.9 percent) to pegylated interferon and RBV.

SAPPHIRE-I and SAPPHIRE-II Results
					SAPPHIRE-I SVR12 (n=473)					SAPPHIRE-II SVR12 (n=297)
All GT1					96.2% (n=455/473)					96.3% (n=286/297)*
GT1a					95.3% (n=307/322)					96.0% (n=166/173)
GT1b					98.0% (n=148/151)					96.7% (n=119/123)
Treatment-experienced (GT1a and GT1b)
Prior null responders					n/a					95.2% (n=139/146)
Prior relapsers					n/a					95.3% (n=82/86)
Prior partial responders					n/a					100.0% (n=65/65)

*Subgenotype could not be determined for one patient

In SAPPHIRE-I, high response rates were seen across patients with certain variable characteristics, including gender, race, body mass index, fibrosis stage and baseline HCV viral load, as some of these patients have historically had a reduced response to treatment.

Discontinuations due to adverse events were reported in 0.6 percent of patients in both arms in SAPPHIRE-I and in 1.0 percent of patients receiving the AbbVie regimen in SAPPHIRE-II and no patients receiving placebo. The most commonly reported treatment-emergent adverse events (>10 percent in either arm) for both SAPPHIRE-I and SAPPHIRE-II were fatigue, headache, nausea, asthenia, insomnia, pruritus and diarrhea. Additional common adverse events occurring in the studies were rash in SAPPHIRE-I and dyspnea, cough and myalgia in SAPPHIRE-II. In SAPPHIRE-I, the adverse events that occurred with a significantly greater frequency in the treatment arm compared to placebo were pruritus, insomnia, diarrhea, nausea and asthenia; in SAPPHIRE-II, only pruritus.

About Study M11-646 (SAPPHIRE-I)
SAPPHIRE-I is a global, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of 12 weeks of treatment with the three direct-acting antiviral regimen with RBV in non-cirrhotic, GT1a and GT1b HCV-infected adult patients new to therapy.
The study population consisted of 631 patients: 473 were randomized to the three direct-acting antiviral regimen with RBV for 12 weeks, and 158 patients were randomized to placebo for the initial 12 weeks. Patients initially randomized to placebo for the first 12 weeks then received open-label treatment with the AbbVie regimen with RBV for 12 weeks.

Of the 473 patients randomized to the three direct-acting antiviral regimen with RBV, one case (0.2 percent) of on-treatment virologic failure occurred and seven patients (1.5 percent) experienced post-treatment relapse. In addition, three patients (0.6 percent) were lost to follow-up and seven patients (1.5 percent) discontinued the study prematurely. Patients lost to follow-up were considered treatment failures.

About Study M13-098 (SAPPHIRE-II)
SAPPHIRE-II is a global, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of 12 weeks of treatment with the three direct-acting antiviral regimen with RBV in non-cirrhotic, GT1a and GT1b HCV-infected, treatment-experienced adult patients who previously failed treatment with pegylated interferon and RBV.
The study population consisted of 394 patients: 297 were randomized to the three direct-acting antiviral regimen with RBV for 12 weeks, and 97 patients were randomized to placebo for the initial 12 weeks. Patients initially randomized to placebo for the first 12 weeks then received open-label treatment with the three direct-acting antiviral regimen with RBV for 12 weeks.

Of the 297 patients randomized to the three direct-acting antiviral regimen with RBV, there were no cases of on-treatment virologic failure and seven patients (2.4 percent) experienced post-treatment relapse. Of these patients, six were prior null responders and one was a prior relapser. Three patients (1.0 percent) prematurely discontinued therapy due to adverse events and one patient (0.3 percent) prematurely discontinued the study.

Additional information about AbbVie’s phase III studies can be found on www.clinicaltrials.gov.

About ABT-450
ABT-450 is an NS3 protease inhibitor discovered through Enanta’s collaboration with AbbVie. AbbVie and Enanta have an agreement to collaborate on the discovery, development and commercialization of HCV NS3 and NS3/4A protease inhibitors. Protease inhibitors play an essential role in the viral life cycle of the hepatitis C virus (HCV). Inhibition of the protease prevents non-structural (NS) proteins from forming and thereby prevents replication and survival of the HCV virus. ABT-450 is part of AbbVie’s investigational regimen for HCV that consists of boosted protease inhibitor ABT-450/ritonavir (referred to as ABT-450/r), NS5A inhibitor ABT-267 and non-nucleoside polymerase inhibitor ABT-333.

Source

Hepatitis C - New Interferon-Free Drugs for Hep C Show High Cure Rates

Related -
Hepatitis C- AbbVie to Present Late-breaker PEARL-III Study at the 21st Conference on Retroviruses and Opportunistic Infections

Medscape Medical News > Conference News

New Interferon-Free Drugs for Hep C Show High Cure Rates

Marcia Frellick

March 04, 2014

 BOSTON — A revolution is happening in the treatment of hepatitis C virus, with new interferon-free drugs bringing cure rates of more than 90%.

Results from several trials were presented on opening day here at the 2014 Conference on Retroviruses and Opportunistic Infections.

PEARL-III

In the PEARL-III trial, treatment-naïve noncirrhotic adults with chronic genotype 1b (GT1b) hepatitis C were treated with an investigational all-oral interferon-free treatment from AbbVie plus ribavirin. After 12 weeks of treatment, sustained virologic response rates reached 99.5%. Even in difficult-to-treat cirrhotic patients, response rates reached 92% to 96%.

"Therapies currently being developed for the treatment of hepatitis C offer patients new options with shorter durations of treatment," said Javier Boix, a spokesperson for AbbVie.

This investigational regimen is appropriate for broad use in all genotype 1 patient populations, and in subgroups with GT1a or GT1b disease, in both treatment-naïve and treatment-experienced patients, Boix told Medscape Medical News. It's also appropriate for "those who typically do not respond well to treatment, such as previous nonresponders to interferon-based therapy and patients with advanced liver fibrosis or cirrhosis," he added.

SYNERGY

This National Institutes of Health (NIH) SYNERGY study looked at 3 different regimens of interferon-free therapy in a difficult-to-treat hepatitis C patient population, 88% of whom were black. After 6 and 12 weeks of treatment, sustained virologic response rates reached 95% to 100%.

"One of the things we learned from this trial is that we can treat people with short durations of therapy," said Anita Kohli, MD, from the NIH in Bethesda, Maryland. "Also, these regimens are very simple. They are 1, 2, or 3 pills once a day," she explained.

PHOTON-1

The phase 3 PHOTON-1 study is the first study of an interferon-free agent in the treatment of patients coinfected with HIV and hepatitis C. After 24 weeks of the once-a-day nucleotide analog polymerase inhibitor sofosbuvir ( Sovaldi), from Gilead, overall sustained virologic response was 76% in patients with genotype 1 hepatitis C, 88% in those with genotype 2 disease, and 90% in those with genotype 3 disease.

In December 2013, the US Food and Drug Administration approved sofosbuvir for the treatment of chronic hepatitis C infection.

Reaching Those in Need

The development of hepatitis C drugs "in the past few years is unprecedented," said Lynn Taylor, MD, from the division of infectious diseases at Miriam Hospital, Brown Medical School, in Providence, Rhode Island.

In the United States, the next step is to build the infrastructure to get the new drugs to the people who need them, she told Medscape Medical News. This will include building up a workforce of people who treat hepatitis C and providing financial incentives and reimbursement reforms.

"Medicare and Medicaid are going to have to pick up the tab for these drugs," because hepatitis C most often occurs in low-income populations. "It's going to be a crisis," she said. "But it will also force people into a rational, deliberate, thoughtful discussion about what we are going to do about hepatitis C."

2014 Conference on Retroviruses and Opportunistic Infections (CROI). Presented March 3, 2014.

Hepatitis C- AbbVie to Present Late-breaker PEARL-III Study at the 21st Conference on Retroviruses and Opportunistic Infections

AbbVie to Present Late-breaker PEARL-III Study in Patients with Chronic Hepatitis C at the 21st Conference on Retroviruses and Opportunistic Infections

-- SVR(12) rates of 99 percent with and without ribavirin were achieved in genotype 1b patients new to treatment

-- Response rates in PEARL-III were also high in specific patient characteristics, such as gender, race and genetics

Mar 3, 2014

BOSTON, March 3, 2014 /PRNewswire/ -- The first detailed results from AbbVie's (NYSE: ABBV) pivotal phase III study, PEARL-III, were presented today as part of the 21st Conference on Retroviruses and Opportunistic Infections (CROI) press conference and will also be presented as a late-breaker at the conference on March 4. PEARL-III evaluated the efficacy and safety of 12 weeks of treatment with AbbVie's investigational therapy with or without ribavirin (RBV) in non-cirrhotic, adult patients with chronic genotype 1b (GT1b) hepatitis C virus (HCV) infection who were new to treatment. 

The PEARL-III study met its primary and secondary endpoints. In the 419-patient study, sustained virologic response rates 12 weeks post-treatment (SVR₁₂) of 99.5 and 99.0 percent were achieved with the AbbVie regimen with and without RBV, respectively. There were no study drug discontinuations due to adverse events.

"Results from PEARL-III are encouraging, as they demonstrate AbbVie's regimen can achieve high rates of SVR, with and without ribavirin across several patient characteristics in those with genotype 1b chronic hepatitis C infection," said Peter Ferenci, M.D., professor of Gastroenterology and Hepatology, Medical University of Vienna.

PEARL-III enrolled patients across different demographics and characteristics. Response rates in patients with certain characteristics (male gender, Black race and IL28B non-CC genotypes) were examined, as these patient populations have historically been associated with having a decreased response to treatment. High response rates were observed across all patients in the study, including those with these characteristics.

"We are excited about the strong PEARL-III results which demonstrate the AbbVie regimen achieved high SVR rates with no discontinuations due to adverse events in patients new to treatment with genotype 1b infection," said Scott Brun, M.D., vice president, pharmaceutical development, AbbVie. "Additionally, with these data, we continue to be on track to begin major regulatory submissions in the second quarter of 2014. AbbVie will continue to disclose additional detailed phase III study results at future scientific congresses and in publications."

About Study M13-961 (PEARL-III)
PEARL-III is a global, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of 12 weeks of treatment with AbbVie's regimen with and without RBV in non-cirrhotic, GT1b HCV-infected, treatment-naive adult patients.

The study population consisted of 419 GT1b treatment-naive patients with no evidence of liver cirrhosis: 209 patients randomized to the regimen without RBV for 12 weeks, and 210 patients randomized to the regimen with RBV for 12 weeks. Following 12 weeks of treatment, 99.0 percent receiving the regimen without RBV (n=207/209) and 99.5 percent receiving the regimen with RBV (n=209/210) achieved SVR₁₂. Patients in the treatment arm without RBV received placebo in substitution for RBV.

Patients with different demographics and characteristics were enrolled in the study, including gender, race (Black vs. non-Black), Hispanic/Latino ethnicity, age, geographic region, body mass index (BMI), liver fibrosis stage, IL28B genotype and viral load.
Across treatment arms in PEARL-III, there were no documented relapses within 12 weeks post-treatment. No on-treatment virologic failures occurred in the treatment arm without RBV and a single virologic failure occurred in the treatment arm with RBV. While all patients in the study completed therapy, two patients in the arm without RBV were lost to follow-up and therefore were considered treatment failures.

The most commonly reported adverse events (>10 percent for either arm) were headache, fatigue, pruritus, nausea and asthenia, with pruritus and nausea occurring at a statistically higher rate in the treatment arm with RBV compared to the arm without RBV. Anemia occurred more commonly among patients in the RBV-containing arm with clinically significant anemia requiring RBV dose reductions occurring in 9 percent of these patients.

Additional information about AbbVie's phase III studies can be found on www.clinicaltrials.gov.

About AbbVie's Investigational HCV Regimen
 The AbbVie investigational regimen consists of the fixed-dose combination of ABT-450/ritonavir (150/100mg) co-formulated with ABT-267 (25mg), dosed once daily, and ABT-333 (250mg) with or without RBV (weight-based), dosed twice daily. The combination of three different mechanisms of action interrupts the HCV replication process with the goal of optimizing SVR rates across different patient populations.

AbbVie's HCV Development Program
The AbbVie HCV clinical development program is intended to advance scientific knowledge and clinical care by investigating an interferon-free, all-oral regimen with and without RBV with the goal of producing high SVR rates in as many patients as possible, including those that typically do not respond well to treatment, such as previous non-responders to interferon-based therapy or patients with advanced liver fibrosis or cirrhosis.
ABT-450 was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals (NASDAQ: ENTA) for HCV protease inhibitors and regimens that include protease inhibitors. ABT-450 is being developed by AbbVie for use in combination with AbbVie's other investigational medicines for the treatment of HCV.

Safety Information for Ribavirin and Ritonavir
Ribavirin and ritonavir are not approved for the investigational use discussed above, and no conclusions can or should be drawn regarding the safety or efficacy of these products for this use.
There are special safety considerations when prescribing these drugs in approved populations.
Ritonavir must not be used with certain medications due to significant drug-drug interactions and in patients with known hypersensitivity to ritonavir or any of its excipients.

Ribavirin monotherapy is not effective for the treatment of chronic hepatitis C virus and must not be used alone for this use. Ribavirin causes significant teratogenic effects and must not be used in women who are pregnant or breast-feeding and in men whose female partners are pregnant. Ribavirin must not be used in patients with a history of severe pre-existing cardiac disease, severe hepatic dysfunction or decompensated cirrhosis of the liver, autoimmune hepatitis, hemoglobinopathies, or in combination with peginterferon alfa-2a in HIV/HCV co-infected patients with cirrhosis and Child-Pugh score greater than or equal to 6.
See approved product labels for more information.

About AbbVie
AbbVie is a global, research-based biopharmaceutical company formed in 2013 following separation from Abbott Laboratories.  The company's mission is to use its expertise, dedicated people and unique approach to innovation to develop and market advanced therapies that address some of the world's most complex and serious diseases.  AbbVie employs approximately 25,000 people worldwide and markets medicines in more than 170 countries.  For further information on the company and its people, portfolio and commitments, please visit www.abbvie.com.  Follow @abbvie on Twitter or view careers on our Facebook or LinkedIn page.

Forward-Looking Statements
Some statements in this news release may be 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," in AbbVie's 2012 Annual Report on Form 10-K/A, 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.

SOURCE AbbVie

For further information: Media: Elizabeth Hoff, +1 (847) 935-4236, elizabeth.hoff@abbvie.com, or Javier Boix, +1 (847) 937-6113, javier.boix@abbvie.com; Investor Relations: Elizabeth Shea, +1 (847) 935-2211, elizabeth.shea@abbvie.com

AbbVie Amazing All-oral Regimen: 100--96 percent cure rates mostly in 12weeks even in patients w-cirrhosis

In AbbVie's Interferon-free late-stage studies of 6 phase 3 trials most HCV genotype 1 participants achieved an impressive 99% cure rates in 12 weeks. AbbVie said it will file for regulatory approval early in the second quarter, expecting to launch in late 2014. 

AbbVie Completes Largest Phase III Program of an All-Oral, Interferon-Free Therapy for the Treatment of HCV Genotype 1

- Ninety-nine percent SVR(12) rates with and without ribavirin in certain patient types

- Even in difficult-to-treat patients (cirrhotic patients) achieved 92-96 percent SVR(12) rates

- AbbVie expects U.S. launch in 2014

 NORTH CHICAGO, Ill., Jan. 31, 2014 /PRNewswire/ -- AbbVie (NYSE: ABBV) announced the completion of its phase III clinical program and released results of four additional studies designed to assess AbbVie's investigational all-oral, interferon-free therapy with and without ribavirin (RBV) in patients with chronic genotype 1 (GT1) hepatitis C virus (HCV) infection. These results described below confirm previously reported AbbVie data and further demonstrate high sustained virologic response rates 12 weeks post treatment (SVR₁₂) and tolerability in these GT1 patients.

AbbVie Phase III Clinical Program Results 

Study	Patients	Treatment Regimen	SVR12
PEARL-II (12 weeks)	GT1b treatment-experienced (N=179)	AbbVie regimen + RBV (n=88)	97% (85/88)
		AbbVie regimen only (n=91)	100% (91/91)
PEARL-III (12 weeks)	GT1b treatment-naive (N=419)	AbbVie regimen + RBV (n=210)	99% (209/210)
		AbbVie regimen only (n=209)	99% (207/209)
PEARL-IV (12 weeks)	GT1a treatment-naive (N=305)	AbbVie regimen + RBV (n=100)	97% (97/100)
		AbbVie regimen only (n=205)	90% (185/205)
TURQUOISE-II (12 & 24 weeks)	GT1 treatment-naive and treatment-experienced with compensated cirrhosis (N=380)	AbbVie regimen + RBV, 12 weeks (n=208)	92% (191/208)
		AbbVie regimen + RBV, 24 weeks (n=172)	96% (165/172)
SAPPHIRE-I (12 weeks)	GT1 treatment-naive (N=631)	AbbVie regimen + RBV (n=473)	96% (455/473)
SAPPHIRE-II (12 weeks)	GT1 treatment-experienced (N=394)	AbbVie regimen + RBV (n=297)	96% (286/297)

"The outcomes of AbbVie's comprehensive phase III studies in 2,300 patients across 25 countries demonstrate how our investigational regimen performs across a broad spectrum of genotype 1 patients, including those with compensated liver cirrhosis," said Scott Brun, M.D., vice president, pharmaceutical development, AbbVie. "The high rates of response and tolerability of our regimen, coupled with the low rates of discontinuation are promising." 

The AbbVie investigational regimen consists of the fixed-dose combination of ABT-450/ritonavir (150/100mg) co-formulated with ABT-267 (25mg), dosed once daily, and ABT-333 (250mg) with or without ribavirin (weight-based), dosed twice daily. The combination of three different mechanisms of action interrupts the HCV replication process with the goal of optimizing SVR rates across different patient populations. In May of 2013, AbbVie's regimen with and without ribavirin for HCV GT1 was designated as a Breakthrough Therapy by the U.S. Food and Drug Administration (FDA). AbbVie is on track to begin major regulatory submissions early in the second quarter of 2014. AbbVie will disclose detailed study results at future scientific congresses and in publications.

About Study M13-389 (PEARL-II)

 PEARL-II is a global, multi-center, randomized, open-label, controlled study to evaluate the efficacy and safety of 12 weeks of treatment with AbbVie's regimen with and without ribavirin in non-cirrhotic, GT1b HCV-infected, treatment-experienced adult patients.

The study population consisted of 179 GT1b treatment-experienced patients with no evidence of liver cirrhosis: 91 patients randomized to the regimen without ribavirin for 12 weeks, and 88 patients randomized to the regimen with ribavirin for 12 weeks. In the ribavirin-free arm, 100 percent (n=91/91) of patients achieved SVR₁₂, while 97 percent (n=85/88) achieved SVR₁₂ in the ribavirin-containing arm.

The most commonly reported adverse events were fatigue and headache. Discontinuations due to adverse events were reported in none of the patients in the ribavirin-free arm and two (2 percent) patients in the ribavirin-containing arm. There were no patients in either arm of the study that experienced virologic relapse or breakthrough.

About Study M13-961 (PEARL-III)

 PEARL-III is a global, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of 12 weeks of treatment with AbbVie's regimen with and without ribavirin in non-cirrhotic, GT1b HCV-infected, treatment-naive adult patients.

The study population consisted of 419 GT1b treatment-naive patients with no evidence of liver cirrhosis: 209 patients randomized to the regimen without ribavirin for 12 weeks, and 210 patients randomized to the regimen with ribavirin for 12 weeks. Following 12 weeks of treatment, 99 percent receiving the regimen without ribavirin (n=207/209) and 99 percent receiving the regimen with ribavirin (n=209/210) achieved SVR₁₂.

The most commonly reported adverse events were headache and fatigue. No patient discontinued study drug due to adverse events. Virologic relapse or breakthrough was noted in none of the patients receiving the regimen without ribavirin and 0.5 percent of patients receiving the regimen with ribavirin.

About Study M14-002 (PEARL-IV)

 PEARL-IV is a global, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of 12 weeks of treatment with AbbVie's regimen with and without ribavirin in non-cirrhotic, GT1a HCV-infected, treatment-naive adult patients.

The study population consisted of 305 GT1a treatment-naive patients with no evidence of liver cirrhosis: 205 patients randomized to the regimen without ribavirin for 12 weeks, and 100 patients randomized to the regimen with ribavirin for 12 weeks. Following 12 weeks of treatment, 90 percent of patients receiving the regimen without ribavirin (n=185/205) and 97 percent receiving the regimen with ribavirin (n=97/100) achieved SVR₁₂.

The most commonly reported adverse events were fatigue, headache and nausea. Discontinuations due to adverse events were reported in two (1 percent) patients receiving the regimen without ribavirin and no patients in the ribavirin-containing arm. Virologic relapse or breakthrough was noted in 8 percent of patients receiving the regimen without ribavirin and 2 percent of patients receiving the regimen with ribavirin.

About Study M13-099 (TURQUOISE-II)

 TURQUOISE-II is the first phase III study completed exclusively in GT1 cirrhotic patients investigating an all-oral, interferon-free regimen. It is a global, multi-center, randomized, open-label study evaluating the efficacy and safety of 12 or 24 weeks of treatment with AbbVie's regimen with ribavirin in cirrhotic, GT1a and GT1b HCV-infected, treatment-naive and treatment-experienced adult patients.

The study population consisted of 380 GT1a and GT1b, treatment-naive and treatment-experienced patients with compensated cirrhosis: 208 patients randomized to the regimen with ribavirin for 12 weeks, and 172 patients randomized to the regimen with ribavirin for 24 weeks. Following 12 weeks of treatment, 92 percent of patients (n=191/208) achieved SVR₁₂. Following 24 weeks of treatment, 96 percent of patients (n=165/172) achieved SVR₁₂.

The most commonly reported adverse events were fatigue, headache and nausea. Discontinuations due to adverse events were reported in four (2 percent) patients receiving the regimen with ribavirin for 12 weeks and four (2 percent) patients in the 24-week arm. Virologic relapse or breakthrough was noted in 6 percent of patients in the 12-week arm and 2 percent in the 24-week arm.

Additional information about AbbVie's phase III studies can be found on www.clinicaltrials.gov.

Globally, approximately 160 million people are chronically infected with hepatitis C[1]. AbbVie's multinational HCV program is the largest all-oral, interferon-free clinical program in GT1 patients being conducted to date[2]. GT1 (with subtypes 1a and 1b) is the most prevalent genotype worldwide.

AbbVie's HCV Development Program
The AbbVie HCV clinical development program is intended to advance scientific knowledge and clinical care by investigating an interferon-free, all-oral regimen with and without ribavirin with the goal of producing high SVR rates in as many patients as possible, including those that typically do not respond well to treatment, such as previous non-responders to interferon-based therapy or patients with advanced liver fibrosis or cirrhosis. 

ABT-450 was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals (NASDAQ: ENTA) for HCV protease inhibitors and regimens that include protease inhibitors. ABT-450 is being developed by AbbVie for use in combination with AbbVie's other investigational medicines for the treatment of HCV.

Safety Information for Ribavirin and Ritonavir
Ribavirin and ritonavir are not approved for the investigational use discussed above, and no conclusions can or should be drawn regarding the safety or efficacy of these products for this use.

There are special safety considerations when prescribing these drugs in approved populations.

Ritonavir must not be used with certain medications due to significant drug-drug interactions and in patients with known hypersensitivity to ritonavir or any of its excipients.

Ribavirin monotherapy is not effective for the treatment of chronic hepatitis C virus and must not be used alone for this use. Ribavirin causes significant teratogenic effects and must not be used in women who are pregnant or breast-feeding and in men whose female partners are pregnant. Ribavirin must not be used in patients with a history of severe pre-existing cardiac disease, severe hepatic dysfunction or decompensated cirrhosis of the liver, autoimmune hepatitis, hemoglobinopathies, or in combination with peginterferon alfa-2a in HIV/HCV co-infected patients with cirrhosis and Child-Pugh score ≥ 6.

See approved product labels for more information.

About AbbVie
AbbVie is a global, research-based biopharmaceutical company formed in 2013 following separation from Abbott Laboratories. The company's mission is to use its expertise, dedicated people and unique approach to innovation to develop and market advanced therapies that address some of the world's most complex and serious diseases. AbbVie employs approximately 25,000 people worldwide and markets medicines in more than 170 countries. For further information on the company and its people, portfolio and commitments, please visit www.abbvie.com. Follow @abbvie on Twitter or view careers on our Facebook or LinkedIn page. 

Forward-Looking Statements

Some statements in this news release may be 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," in AbbVie's 2012 Annual Report on Form 10-K/A, 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] Lavanchy D. Evolving epidemiology of hepatitis C virus. Clin Microbiol Infect. 2011; 17(2):107-15.

[2] Comparison based on review of data from www.clinicaltrials.gov for phase 3a programs of Gilead, BMS and BI as of November 15, 2013. 

SOURCE AbbVie

RELATED LINKS
http://www.abbvie.com

Only just the beginning of the end of hepatitis C

The Lancet, Volume 383, Issue 9914, Page 281, 25 January 2014

doi:10.1016/S0140-6736(14)60087-8 Cite or Link Using DOI
Copyright © 2014 Elsevier Ltd All rights reserved.

Editorial - PDF Download 

Only just the beginning of the end of hepatitis C
 
2014 marks the 25th anniversary of the identification of the hepatitis C virus (HCV). HCV infection continues to be a major global health problem. Unlike many chronic diseases, hepatitis C can be cured, but it is difficult to treat, not all patients are responsive, side-effects can be severe, and progression to end-stage liver disease and liver cancer is common. Over the past few years, new medicines for HCV infection have begun to transform the treatment landscape, and, just in the past few months alone, the development of new regimens has been so successful that disease experts are heralding an era where all patients can be cured, even debating whether eradication is possible.

HCV has six major genotypes and the infecting genotype determines the treatment response and duration. Genotypes 1—3 have a worldwide distribution, but genotype 1 predominates in North America, Europe, and Japan, hence pharmaceutical research to treat this genotype has been preferred to others.

The new treatment modalities are once-daily oral combination regimens with optional inclusion of ribavirin and are pegylated interferon (peginterferon) free, so multiple tablets and injections are no longer needed. The novel agents are known as direct-acting antivirals (DAAs). In two phase 2 clinical trials published last week, the DAAs, sofosbuvir and daclatasvir, and the investigational DAAs, ABT-450, ABT-267, and ABT-333 in combination with known protease inhibitors, were shown to achieve high viral clearance response rates (83—100%) in previously treated and previously untreated patients with HCV genotype 1 with a short duration of therapy (12 weeks vs 48 weeks), together with a favourable safety profile compared with the current standard peginterferon based treatments.

Patients with HCV genotypes 2 and 3 also responded well to treatment and there was minimal need for clinical and laboratory monitoring. Testing of other promising DAAs is underway. Results are expected within the next 2 years. Rapid regulatory approval of sofosbuvir in the USA and Europe (and an expedited review of daclatasvir) have been accompanied by reports of promises from companies to ensure that access is achieved as quickly as possible. But given 90% of the estimated 184 million people with hepatitis C live in low-income and middle-income countries, how available and accessible will these new medicines be globally?

The main drawback of these new agents is the huge price tag, which will make treatment out of reach for people in the developed and developing world. Indeed, current treatment uptake is also impeded by cost. One 12 week course of sofosbuvir will cost US$84 000, even though the scientist involved in formulating sofosbuvir, Raymond Schinazi, estimates costs at just $1400. An even lower price was shown by Andrew Hill and colleagues in a recent study. Based on the fact that the new hepatitis C treatments are comparable in molecular structure and chemistry to HIV antiretrovirals, the authors used the same market dynamics to determine the minimum cost to manufacture them, which was $100—250 per 12 week treatment course; they concluded that at these low prices, widespread access to these new medicines is feasible within 15 years. Although manufacturers are likely to offer low-income countries steep discounts, around 75% of people with hepatitis C live in middle-income countries regarded as emerging markets by companies, and so are unlikely to benefit from the kind of discounts needed to make treatment available. Interestingly, the sofosbuvir patent application is currently under challenge in India, and if upheld will allow Indian generic drug companies to enter the market and drive major price reductions as seen with HIV/AIDS medicines.

The other concern is the limited testing of these new treatments on less common genotypes and marginalised populations disproportionately affected by HCV infection. For example, there has been minimal testing among those co-infected with HIV. Although the field is likely to see pan-genotypic treatments that clear all genotypes, and will also remove the need for a complex diagnostic, many countries are still years away from these scenarios.

The need for a global plan for hepatitis C is imperative. It should include research and operational priorities, and establish global funding mechanisms. Countries are only likely to develop national plans for hepatitis C when treatments become more affordable. Last year, Tido von Schoen-Angerer and colleagues in a Lancet letter rightly argued that UNITAID—which has successfully lowered prices of HIV treatments—should do the same for hepatitis C medicines. Lessons from HIV/AIDS will be instructive for the hepatitis C field, as will political and community mobilisation to ensure these treatments reach those in most need.

The Lancet
Photo Credit - Ramon Andrade 3DCiencia/Science Photo Library