Gilead's Sofosbuvir/Velpatasvir and SOF/VEL Plus GS-9857 at The International Liver CongressTM

Gilead Announces Multiple Scientific Presentations Demonstrating Broad Utility of Sofosbuvir-Based Hepatitis C Therapies

– Studies Highlight Progress with Approved Therapies and Investigational Pangenotypic Regimens, Including Sofosbuvir/Velpatasvir (SOF/VEL) and SOF/VEL Plus GS-9857 –

   

FOSTER CITY, Calif.--(BUSINESS WIRE)--Apr. 16, 2016-- Gilead Sciences, Inc. (NASDAQ: GILD) today announced results from several Phase 2 and Phase 3 studies evaluating its two investigational, pangenotypic, fixed-dose combination therapies for the treatment of chronic hepatitis C virus (HCV) infection, as well as new data highlighting the potential use of Harvoni^® (ledipasvir/sofosbuvir) in adolescents aged 12 to 17. Data were presented this week at The International Liver Congress^TM 2016 in Barcelona, Spain.
   
“The data presented this week continue to underscore the high cure rates and safety of our sofosbuvir-based HCV therapies, and support their utility across all patient HCV genotypes and disease stages,” said Norbert Bischofberger, PhD, Executive Vice President of Research and Development and Chief Scientific Officer at Gilead. “We are pleased to have the opportunity to further characterize the pangenotypic profiles of our two new investigational fixed-dose combinations, sofosbuvir/velpatasvir and sofosbuvir/velpatasvir plus GS-9857, and to highlight results from the first study to evaluate interferon-free HCV therapy in adolescents.”
   
Sofosbuvir/Velpatasvir (SOF/VEL)
Results from the open-label, Phase 3 ASTRAL-5 study (PS104), led by David L. Wyles, MD, Associate Professor of Medicine, Division of Infectious Diseases, University of California, San Diego, California, evaluating once-daily SOF/VEL for 12 weeks among patients with HCV genotype 1-6 who are co-infected with HIV demonstrated that SOF/VEL was well-tolerated and resulted in high SVR12 rates. The SVR12 rate was 95 percent (n=99/104) overall, and 100 percent (n=19/19) and 97 percent (n=28/29) in patients with cirrhosis and prior treatment-failure, respectively. Two patients relapsed, while three patients were lost to follow up or withdrew consent. Two patients achieved SVR4 but have not yet returned for the post-treatment week 12 visit. The most common adverse events (>10 percent) were fatigue and headache.
SOF/VEL is currently being evaluated by regulatory agencies in the United States, Europe and Canada.
   
Sofosbuvir/Velpatasvir (SOF/VEL) Plus GS-9857
Data from three Phase 2 trials evaluating SOF/VEL plus GS-9857, a pangenotypic protease inhibitor, (Studies GS-US-367-1168 and GS-US-367-1169 and TRILOGY-3) also were selected for presentation.
   
Studies 1168 and 1169
Studies 1168 and 1169 evaluated 6 and 8 weeks of SOF/VEL plus GS-9857, with or without ribavirin (RBV), among treatment-naïve patients and 12 weeks of SOF/VEL plus GS-9857 among patients who failed prior treatment including those previously exposed to a direct acting antiviral (DAA) regimen. Study 1168 evaluated 197 genotype 1 patients and Study 1169 evaluated 128 genotype 2-6 patients.
   

•		Treatment-naïve patients: Poster SAT-138 highlighted combined safety and efficacy results from Studies 1168 and 1169 evaluating SOF/VEL plus GS-9857, with or without ribavirin, in genotype 1-6, treatment-naïve patients, with and without cirrhosis.  SVR12 rates were:
				SOF/VEL plus GS-9857				SOF/VEL plus GS-9857 with RBV
				6 weeks		8 weeks		8 weeks
		SVR12		79% (n=53/67)		96% (n=95/99)		81% (n=25/31)
		The most common adverse events (>10 percent) across the three study arms were headache, nausea, fatigue, diarrhea and anemia.
•		Treatment-experienced patients: Oral presentation PS008 highlighted combined safety and efficacy results from Studies 1168 and 1169 evaluating 12 weeks of SOF/VEL plus GS-9857 in genotype 1-6, treatment-experienced patients.  Twenty-seven percent of patients were NS5A inhibitor-experienced, 52 percent were non-NS5A inhibitor, DAA-experienced and 21 percent failed interferon-based treatment without a DAA.  Overall, the SVR12 rate was 99 percent (n=127/128). One genotype 3 patient with cirrhosis who had failed prior treatment with sofosbuvir plus pegylated interferon/ribavirin relapsed. Frequently reported adverse events (>10 percent) were headache, fatigue, diarrhea and nausea.

Studies 1168 and 1169 were led by Edward J. Gane, MD, Auckland City Hospital, Auckland, New Zealand (SAT-138); and Eric Lawitz, MD, Texas Liver Institute, University of Texas Health Science Center, San Antonio, Texas (PS008), respectively.
   
TRILOGY-3
A late-breaker oral presentation (PS021) featuring data from a Phase 2 trial, led by Dr. Lawitz, evaluated 12 weeks of a fixed-dose combination of SOF/VEL/GS-9857, with or without RBV, among genotype 1, DAA-experienced, HCV-infected patients, including patients with cirrhosis. One hundred percent (n=24/24) of patients receiving 12 weeks of therapy with SOF/VEL/GS-9857 and 96 percent (n=24/25) of patients receiving SOF/VEL/GS-9857 plus RBV achieved SVR12. Among the 49 patients in this trial, 41 percent had prior exposure to an NS5A inhibitor and 47 percent previously received at least two classes of DAA. The most common adverse events (>10 percent) across both treatment arms were fatigue and anemia.
Based on these data a fixed-dose combination of SOF/VEL/GS-9857 is being evaluated in four Phase 3 studies (POLARIS-1, POLARIS-2, POLARIS-3 and POLARIS-4). SOF/VEL/GS-9857 has been granted a Breakthrough Therapy designation by the U.S. Food and Drug Administration for the treatment of chronic genotype 1 HCV patients who have previously failed an NS5A inhibitor-containing regimen.
   
Harvoni
Harvoni is the first single tablet HCV regimen approved in the United States for use in a broad range of patient populations, including HCV genotypes 1, 4, 5 and 6, HCV/HIV-1 coinfection, HCV genotype 1 and 4 liver transplant recipients and genotype 1-infected patients with decompensated cirrhosis.
Data from an evaluation of Harvoni in genotype 1 HCV-infected adolescents aged 12 to 17 have been selected for presentation in a late breaker oral session (LB-4597). Presented by Sanjay Bansal, MD, MRCPCH, Kings College Hospital, London, United Kingdom, and led by Kathleen B. Schwarz, MD, Pediatric Liver Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, the Phase 2 study demonstrated that Harvoni is well tolerated and results in high SVR12 in this population. Of the 100 patients enrolled, 97 percent (n=97/100) achieved SVR12. The three patients who did not achieve SVR12 were lost to follow up; no patients experienced virologic failure. The most common adverse events were headache, diarrhea and fatigue. Further evaluation of Harvoni in a pediatric population of children aged 3 to 11 is ongoing.
Further information about the clinical studies described above can be found at www.clinicaltrials.gov.
Uses for Harvoni in certain HCV patient populations highlighted above are investigational and have not been determined to be safe or efficacious. SOF/VEL and SOF/VEL/GS-9857 are investigational products and have not been determined to be safe or efficacious.
   
Important Safety Information for Harvoni
Contraindications
If Harvoni is used in combination with ribavirin (RBV), all contraindications, warnings and precautions, in particular pregnancy avoidance, and adverse reactions to RBV also apply. Refer to RBV prescribing information.
   
Warnings and Precautions
Risk of Serious Symptomatic Bradycardia When Coadministered with Amiodarone: Amiodarone is not recommended for use with Harvoni due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia.
   
Risk of Reduced Therapeutic Effect of Harvoni Due to P-gp Inducers: Rifampin and St. John’s wort are not recommended for use with Harvoni as they may significantly decrease ledipasvir and sofosbuvir plasma concentrations.
   
Related Products Not Recommended: Harvoni is not recommended for use with other products containing sofosbuvir (Sovaldi).
Adverse Reactions
Most common (≥10%, all grades) adverse reactions were fatigue, headache and asthenia.
   
Drug Interactions
In addition to rifampin and St. John’s wort, co-administration of Harvoni is also not recommended with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, and tipranavir/ritonavir. Such co-administration is expected to decrease the concentration of ledipasvir and sofosbuvir, reducing the therapeutic effect of Harvoni.
Co-administration of Harvoni is not recommended with simeprevir due to increased concentrations of ledipasvir and simeprevir. Co-administration is also not recommended with rosuvastatin or co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate due to increased concentrations of rosuvastatin and tenofovir, respectively.
Consult the full Prescribing Information for Harvoni for more information on potentially significant drug interactions, including clinical comments.
   
About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company’s mission is to advance the care of patients suffering from life-threatening diseases. Gilead has operations in more than 30 countries worldwide, with headquarters in Foster City, California.
   
Forward-Looking Statement
This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the risk that Gilead may observe unfavorable results from additional clinical trials involving SOF/VEL, SOF/VEL/GS-9857 and Harvoni in certain patient populations, including adolescents aged 12 to 18. In addition, the regulatory filings for SOF/VEL and SOF/VEL/GS-9857 may not be approved by regulatory agencies, and marketing approvals, if granted, may have significant limitations on their use. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead’s Annual Report on Form 10-K for the year ended December 31, 2015, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.
   

U.S. full Prescribing Information for Harvoni is available at www.gilead.com.

Harvoni is a registered trademark of Gilead Sciences, Inc. or its related companies.

For more information on Gilead Sciences, please visit the company’s website at www.gilead.com, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.

AbbVie ABT-493 and ABT-530 For Genotypes 1-6: New Phase 2 Data Presented At The International Liver Congress

AbbVie Presents New Phase 2 Data for Investigational, Once-Daily, Ribavirin-Free, Pan-Genotypic Regimen of ABT-493 and ABT-530 for Hepatitis C Genotypes 1-6

Apr 16, 2016

- 97-98 percent SVR12 achieved with eight weeks of ABT-493 and ABT-530 in genotypes 1-3 hepatitis C virus patients without cirrhosis in SURVEYOR-1 and 2 studies(1,2)
- 100 percent SVR12 achieved with 12 weeks of treatment in difficult-to-treat genotype 3 patients with compensated cirrhosis (Child-Pugh A) new to therapy (3)
- 100 percent SVR12 achieved with 12 weeks of treatment in genotypes 4-6 patients without cirrhosis; eight-week duration investigated in this ongoing study (4)

BARCELONA, April 16, 2016 /PRNewswire/ -- AbbVie (NYSE: ABBV), a global biopharmaceutical company, today announced that with eight weeks of treatment, 97-98 percent of genotype 1-3 (GT1-3) chronic hepatitis C virus (HCV) infected patients without cirrhosis treated with AbbVie's investigational, once-daily, ribavirin (RBV)-free, pan-genotypic regimen of ABT-493 and ABT-530 achieved sustained virologic response at 12 weeks post-treatment (SVR₁₂).^1,2 Results for GT1 (n=33/34), GT2 (n=53/54) and treatment-naïve GT3 (n=28/29) patients were based on an Intent-to-Treat (ITT) analysis.^1,2 Additionally, 100 percent (n=34/34) of genotype 4-6 (GT4-6) chronic HCV infected patients without cirrhosis achieved SVR₁₂ with 12 weeks of treatment.⁴ These new data from the Phase 2 SURVEYOR-1 and SURVEYOR-2 studies will be presented at The International Liver Congress™ (ILC) 2016 in Barcelona, Spain.

"These results move us closer to our ultimate goal of providing a treatment option for as many hepatitis C patients as possible. We will continue to examine our investigational, pan-genotypic regimen through our dedicated clinical trial program, including an eight-week duration across all genotypes," said Rob Scott, M.D., vice president, development and chief medical officer, AbbVie.
In separate late-breaking data from the SURVEYOR-2 study, 100 percent of GT3 chronic HCV infected patients with compensated cirrhosis (Child-Pugh A) new to therapy achieved SVR₁₂ with 12 weeks of treatment both with and without RBV (n=24/24 in each arm).³ No patients discontinued treatment due to adverse events.³ Data in GT3 chronic HCV infected patients with and without cirrhosis were featured in the official ILC 2016 press program.

"The recent evolution in hepatitis C treatment has resulted in high cure rates for many patients with specific genotypes, but there remain distinct areas of unmet need," said Paul Kwo, M.D., professor of medicine at the Indiana University School of Medicine. "These new data show us the potential of ABT-493 and ABT-530 in genotype 3 patients new to therapy even with the added complication of compensated cirrhosis."

In a pooled analysis of 531 patients across both SURVEYOR studies, of five treatment regimens of ABT-493 and ABT-530 evaluated, the most commonly reported adverse events were fatigue (18 percent), headache (17 percent), nausea (13 percent) and diarrhea (10 percent).⁵ Three patients across all study arms evaluated to date, two of whom received RBV, discontinued study drugs early due to adverse events.⁵

Overview of SURVEYOR-1 and SURVEYOR-2 Clinical Data Presented at ILC:
Patient Profile/Study	Patient number (n)/ Patient Population	Duration of Treatment	Treatment Regimen	SVR12 Rates ITT*
GT1 Non-cirrhotic1 SURVEYOR-1	n=34 Treatment-naïve=85% pegIFN/RBV treatment experienced=15%	8 weeks	ABT-493 (300mg) + ABT-530 (120mg) once daily	97% (n=33/34)
GT2 Non-cirrhotic1 SURVEYOR-2	n=54 Treatment-naïve=87% pegIFN/RBV treatment experienced=13%	8 weeks	ABT-493 (300mg) + ABT-530 (120mg) once daily	98% (n=53/54)
GT3 Non-cirrhotic2 SURVEYOR-2	n=29 Treatment-naïve =100%	8 weeks	ABT-493 (300mg) + ABT-530 (120mg) once daily	97% (n=28/29)
GT3 Cirrhotic3 (Child-Pugh A)  SURVEYOR-2	n=24 Treatment-naïve= 100%	12 weeks	ABT-493 (300mg) + ABT-530 (120mg) without RBV once daily	100% (n=24/24)
	n=24 Treatment-naïve=100%	12 weeks	ABT-493 (300mg) + ABT-530 (120mg) +  RBV (800mg) once daily	100% (n=24/24)
GT 4,5,6 Non-cirrhotic4 SURVEYOR-1	n=34 (GT4=22; GT5=1; GT6=11) Treatment-naïve=85% pegIFN/RBV treatment experienced=15%	12 weeks	ABT-493 (300mg) + ABT-530 (120mg) once daily	100% (n=34/34)

*	Intent-to-treat (ITT) population is defined as all patients who received at least one dose of the study drugs

About SURVEYOR-1^1,4,5
SURVEYOR-1 is an ongoing Phase 2 two-part study designed to evaluate the safety and efficacy of ABT-493 and ABT-530, with and without RBV, for eight to 12 weeks, in cirrhotic and non-cirrhotic adult genotype 1 patients, and non-cirrhotic adult patients with genotypes 4, 5 or 6 chronic HCV infection who were new to therapy or did not respond to previous treatment with pegylated interferon (pegIFN)/RBV (null responder).

About SURVEYOR-2^1,2,3,5
SURVEYOR-2 is an ongoing Phase 2, four-part study designed to evaluate the safety and efficacy of ABT-493 and ABT-530, with or without RBV, in adult patients with genotypes 2, 3, 4, 5 or 6 chronic HCV infection who were new to therapy or had failed previous treatment with pegylated interferon (pegIFN)/RBV.
The primary endpoint of both studies is the percentage of subjects achieving SVR₁₂.
Safety and efficacy data for Part 1 of the studies were presented at The Liver Meeting® 2015, the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in San Francisco.

About pooled safety analysis of SURVEYOR-1 and SURVEYOR-2⁵
531 patients were included in this safety analysis: 26 percent GT1, 24 percent GT2, 43 percent GT3, and 6 percent with GT4, 5 or 6 infection. Patients across genotypes received ABT-493/ABT-530 at five doses: 300/120mg (n=258), 300/120mg with RBV (n=27), 200/120mg (n=121), 200/120mg with RBV (n=56), and 200/40mg (n=69).

About AbbVie's HCV Clinical Development Program
AbbVie's HCV clinical development program is intended to advance scientific knowledge and the clinical care of people with chronic HCV infection by investigating pan-genotypic (genotypes 1-6), all-oral, ribavirin-free, once-daily treatment for 12 weeks. An eight-week treatment duration with ABT-493 and ABT-530 will be investigated across all genotypes in our comprehensive Phase 2/Phase 3 clinical trial program, which focuses on areas of ongoing need in HCV.
AbbVie's investigational regimen includes 300mg ABT-493, an NS3/4A protease inhibitor, and 120mg ABT-530, an NS5A inhibitor.
ABT-493 was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals (NASDAQ: ENTA) for HCV protease inhibitors and regimens that include protease inhibitors.

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. Together with its wholly-owned subsidiary, Pharmacyclics, AbbVie employs more than 28,000 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.

¹ Poordad, F et al. High SVR Rates with the Combination of ABT-493 + ABT-530 for 8 Weeks in Non-Cirrhotic Patients with HCV Genotype 1 or 2 Infection. Poster presentation #SAT-157; presented at The International Liver Congress™ (ILC), the Annual Meeting of the European Association for the Study of the Liver (EASL) in Barcelona, Spain, April 13-17, 2016.
² Muir, A et al. High SVR Rates with ABT-493 + ABT-530 Co-Administered for 8 Weeks in Non-Cirrhotic Patients with HCV Genotype 3 Infection. Oral presentation #PS098; presented at The International Liver Congress™ (ILC), the Annual Meeting of the European Association for the Study of the Liver (EASL) in Barcelona, Spain, April 13-17, 2016.
³ Kwo, P et al. 100% SVR₁₂ with ABT-493 And ABT-530 with or without Ribavirin in Treatment-Naïve HCV Genotype 3-Infected Patients with Cirrhosis; Late Breaker presentation #LB01; presented at The International Liver Congress™ (ILC), the Annual Meeting of the European Association for the Study of the Liver (EASL) in Barcelona, Spain, April 13-17, 2016
⁴ Gane, E et al. 100% SVR₄ and Favorable Safety of ABT-493 + ABT-530 Administered for 12 Weeks in Non-Cirrhotic Patients with Genotypes 4,5, or 6 Infection (SURVEYOR-I). Poster presentation #SAT-137; presented at The International Liver Congress™ (ILC), the Annual Meeting of the European Association for the Study of the Liver (EASL) in Barcelona, Spain, April 13-17, 2016.
⁵ Kwo, P et al. Safety of ABT-493 and ABT-530 Co-Administered in Patients with HCV Genotype 1-6 Infection: Results From the SURVEYOR-I and SURVEYOR-II Studies; Poster presentation #SAT-239; presented at The International Liver Congress™ (ILC), the Annual Meeting of the European Association for the Study of the Liver (EASL) in Barcelona, Spain, April 13-17, 2016.

SOURCE AbbVie

LC2016/Short treatment with sofosbuvir and ledipasvir over only six weeks is sufficient to cure acute Hepatitis C

Scientists find a way to cure Hepatitis C with six weeks of treatment
April 16, 2016
Press Releases

Short treatment with sofosbuvir and ledipasvir over only six weeks is sufficient to cure acute Hepatitis C (HCV) 

April 16, 2016, Barcelona, Spain: A pilot study presented today found that all patients with acute HCV who were treated with a direct-acting antiviral treatment over a ‘short-duration’ of six weeks had undetectable HCV after a 12 week follow-up. The investigator-initiated study, presented at The International Liver CongressTM in Barcelona, Spain, demonstrated that the combination of sofosbuvir and ledipasvir for only six weeks is sufficient to treat patients with acute HCV.

Those infected with HCV usually develop acute Hepatitis C, which spontaneously clears in 10 to 50% of infected persons. Early diagnosis of HCV infection is rare and the disease may go unnoticed until patients have already developed serious liver damage.1 Sofosbuvir and ledipasvir is one possible regimen for treatment of patients with chronic HCV. Sustained virologic response (SVR) is greater than 95% with a 12-week course of this treatment.2

“Given the high cost of sofosbuvir and ledipasvir, and the associated side effects that occur during treatment, we set out to assess whether shortened treatment duration could be an effective option for acute Hepatitis C patients,” said Katja Deterding from Hannover Medical School, Germany and study author. “Our research demonstrates that not only is the combination of sofosbuvir and ledipasvir safe, well tolerated and effective in acute HCV genotype 1 patients who have severe liver disease with very high liver enzymes, but a shorter treatment duration does not appear to hinder efficacy,” confirmed Professor Heiner Wedemeyer, the senior author of this study.

The German pilot study, performed by the German HepNet Study-House included 20 patients. Risk factors of HCV infection among the study members included; sexual transmission (n=11), medical procedures/needle stick injury (n=5), drug use (n=1), and nail treatment complications (n=1). The causes were unspecified for the remaining two patients.

All 20 patients completed six weeks of sofosbuvir and ledipasvir without ribavirin. At the 12 week follow up, all 20 patients had undetectable HCV and achieved SVR (100%). Fatigue was the most frequent side effect reported by study members (30%).

“These exciting findings open up short and cost-effective treatment options that could prevent the spread of HCV in high risk populations,” said Professor Frank Tacke, EASL Governing Board member. “We look forward to seeing this pilot study extended so the findings can be validated and then hopefully used as a tool to change clinical practice for the better.”

LC2016/ ‘Personalisation’ of direct-acting antiviral treatment could help eradicate Hepatitis C virus from the body

New study challenges the concept of treatment failure in Hepatitis C
April 16, 2016
Press Releases

‘Personalisation’ of direct-acting antiviral treatment could help eradicate Hepatitis C virus from the body

Re-treatment was started in 29% (n=57/195) of patients with genotype 1; the majority of these patients had failed treatment with the combination of simeprevir and sofosbuvir, and were re-treated with the combinations of ledipasvir and sofosbuvir or paritaprevir, ombitasvir, and dasabuvir. SVR12 was achieved in 90% of the re-treated patients with genotype 1. In the genotype 3 group, 23% (n=16/69) of patients were re-treated with sofosbuvir, daclatasvir ± ribavirin. All of the re-treated patients with available follow-up data achieved SVR12.

April 16, 2016, Barcelona, Spain: Data presented today demonstrate that choosing a different combination of direct-acting antiviral (DAA) treatment for Hepatitis C can eradicate the virus at four weeks in patients who had already failed on previous medication regimens. The results were presented at The International Liver CongressTM in Barcelona, Spain and suggest that with the amount of DAAs available, the right combinations must be chosen for the right patients in order to eradicate the virus from the body.

Between 130 and 150 million people globally have chronic Hepatitis C virus (HCV) infection.1 It is estimated that 15 million people in the World Health Organization’s EU Region are living with Hepatitis C, representing 2% of adults.2 Direct-acting antivirals are the treatment of choice for HCV, and these medicines have been used to treat and cure almost all patients.3,4,5,6

“As a result of the emergence of resistance associated variants, the re-treatment of patients with HCV remains challenging,” said Dr Johannes Vermehren, Universitätsklinikum Frankfurt, Germany and lead author of the study. “While treatment failure was observed in all of the various medication regimens, there is hope for these patients that re-treatment with differing combinations can be effective.”

The German study drew patients with failure to DAAs from a large European HCV DAA-resistance database made up of more than 3,500 patients. Patients were included if they had received interferon-free DAA regimens. Treatment combinations were specific to HCV genotype.

The study identified 310 patients with failure to direct-acting antivirals. Among patients with genotype 1 and 3, 90% and 39% had resistance associated variants (RAVs), respectively.

Re-treatment was started in 29% (n=57/195) of patients with genotype 1; the majority of these patients had failed treatment with the combination of simeprevir and sofosbuvir, and were re-treated with the combinations of ledipasvir and sofosbuvir or paritaprevir, ombitasvir, and dasabuvir. SVR12 was achieved in 90% of the re-treated patients with genotype 1. In the genotype 3 group, 23% (n=16/69) of patients were re-treated with sofosbuvir, daclatasvir ± ribavirin. All of the re-treated patients with available follow-up data achieved SVR12.

“The concept of failed Hepatitis C treatment may be increasingly out of date. It may indicate that we have not yet found the right combination of drugs to eradicate the virus in a particular patient. With the plethora of direct-acting antivirals available, the medical community must work to find the right combination of medicines for the right patient,” said Professor Frank Tacke, member of the EASL Governing Board.

ILC2016/Ledipasvir and sofosbuvir: Efficacy of all-oral treatment regimens in adolescents with Hepatitis C virus infection

New study demonstrates efficacy of all-oral treatment regimens in adolescents with Hepatitis C virus infection
April 16, 2016
Press Releases

Data suggest that all oral treatment regimen may have a role in the treatment of adolescent patients

April 16, 2016, Barcelona, Spain: Adolescents with Hepatitis C (HCV) could benefit from a combination of direct-acting antivirals, according to new data presented today at The International Liver Congress™ 2016 in Barcelona, Spain. The study demonstrated that adolescent patients with HCV genotype 1 aged 12 to 18 years who were treated for 12 weeks with a fixed dose combination of ledipasvir and sofosbuvir attained high sustained virologic response (SVR) rates.

Hepatitis C causes about 86,000 deaths per year in World Health Organization (WHO) European (EU) Region.1 Between 130 and 150 million people globally have chronic Hepatitis C infection,2 including approximately 15 million people in the EU.3 Children represent approximately 10% of those infected with the Hepatitis C virus (HCV), however some of these children have chronic disease and are at risk for complications. While direct-acting antivirals have been used to treat and cure almost all patients with HCV,4,5,6,7 they have been exclusively studied in adults, leaving adolescents to take pegylated interferon with ribavirin for 24 to 48 weeks.

“While there have been many studies investigating different treatment regimens for Hepatitis C in adults, data in adolescents have been lacking,” says study presenting author Dr Sanjay Bansal, Consultant Paediatric Hepatologist at King’s College Hospital, London and author of the study. “These data in HCV-infected adolescents confirm that this drug combination is effective in a younger population and has a more favourable side-effect profile than the treatments currently licensed for teenagers.”

The study included 100 patients aged between 12 and 18 years, infected with HCV genotype 1. In the open-label study, 100 patients received treatment with ledipasvir and sofosbuvir (90mg/400mg) once daily over a 12 week period. The primary efficacy endpoint was sustained viral response at 12 weeks post-treatment (SVR12).

Results from this study showed that of the 100 patients enrolled, 97% achieved SVR12 (n=97); the 3 patients who did not achieve SVR12 were lost to follow-up. No serious adverse events were reported, and the most common adverse events (reported by ≥10% of subjects) were headache (27%), diarrhoea (14%), fatigue (13%), nausea (12%), cough (10%) and vomiting (10%).

“These are very promising data for a patient group that has until now been excluded from the studies of newer agents in HCV infection,” said Professor Franck Tacke, Member of the EASL Governing Board. “We hope that this treatment regimen will provide these young patients with relief from this challenging condition.”

AbbVie's Investigational Regimen ABT-493 and ABT-530 Shows High SVR In HCV Genotype 1 Patients Who Failed Previous Therapy

AbbVie's Investigational, Pan-Genotypic Regimen of ABT-493 and ABT-530 Shows High SVR Rates in Genotype 1 Hepatitis C Patients Who Failed Previous Therapy with Direct-Acting Antivirals
Apr 15, 2016

- 95 percent of patients achieved SVR12 with 12 weeks of ABT-493 and ABT-530 with and without RBV in GT1 chronic HCV infected patients without cirrhosis who failed previous therapy with DAAs in a modified intent-to-treat analysis
- 91 percent achieved SVR12 with RBV in the primary intent-to-treat analysis; 86 percent achieved SVR12 without RBV

BARCELONA, April 15, 2016 /PRNewswire/ -- AbbVie (NYSE: ABBV), a global biopharmaceutical company, today announced that 91 percent (n=20/22) of genotype 1 (GT1) chronic hepatitis C virus (HCV) infected patients who failed previous therapy with direct-acting antivirals (DAAs) achieved SVR12 with 12 weeks of ABT-493 and ABT-530 with ribavirin (RBV) in the primary intent-to-treat analysis. Additionally, 86 percent (n=19/22) of GT1 patients who received ABT-493 and ABT-530 without RBV, achieved SVR12.1 SVR12 was achieved in 95 percent of patients with and without RBV (n=20/21, n=19/20; respectively) in a modified intent-to-treat analysis, excluding patients who did not achieve SVR for reasons other than virologic failure.

The results were evaluated in the ongoing MAGELLAN-1 study of AbbVie's once-daily, investigational, pan-genotypic regimen of co-formulated ABT-493 (300mg) and ABT-530 (120mg) for the retreatment of non-cirrhotic patients with GT1 chronic HCV who have failed previous therapy with DAAs. These data will be presented today at The International Liver Congress™ (ILC) 2016 in Barcelona, Spain.

"Retreatment options for those patients who have previously failed therapy are limited, and present a particular challenge for treating physicians," said Fred Poordad, M.D., vice president of academic and clinical affairs at The Texas Liver Institute in San Antonio. "The high SVR rates seen in the ongoing MAGELLAN-1 study are significant as they show promise in addressing this particular clinical challenge."

No patients discontinued treatment due to adverse events, and two patients experienced virologic failure, one from each arm.1 The most common adverse events (?10 percent of patients overall; n=44) were headache (30 percent), fatigue (27 percent) and nausea (20 percent).1

"While high virologic cure rates have been demonstrated in clinical studies with current DAA regimens, we recognize that not all patients achieve a cure," said Rob Scott, M.D., vice president, development and chief medical officer, AbbVie. "Through our ongoing clinical development program, we are striving to give HCV patients a potential option for retreatment."

About MAGELLAN-11
MAGELLAN-1 is an ongoing Phase 2, randomized, open-label multicenter study to evaluate the efficacy, safety and pharmacokinetics of ABT-493 and ABT-530, with and without RBV, in adults with GT1 and genotypes 4-6 chronic HCV infection who failed a prior DAA-containing therapy.

In Part 1 of the study, 50 GT1 patients without cirrhosis who previously failed therapy containing a protease inhibitor and/or NS5A inhibitor, with or without a NS5B polymerase inhibitor, were randomized to receive once-daily ABT-493 and ABT-530 at doses of 200/80mg (Arm A), 300/120mg with 800mg RBV (Arm B), or 300/120mg without RBV (Arm C), for 12 weeks. The primary efficacy endpoint was SVR12. Patients who failed previous treatment for reasons other than breakthrough or relapse were excluded. Deep sequencing (Illumina MiSeq) revealed pre-existing resistance-associated variants (RAVs) in 41 patients (82 percent), 15 in NS3, 10 in NS5A, and 16 with RAVs in both targets. Data presented at ILC 2016 were based on an analysis of the intent-to-treat population.

Data from the first six patients enrolled in Arm A (once-daily ABT-493 and ABT-530 at doses of 200/80mg) showed 100 percent achieved SVR12. Additional patients were enrolled and received study drug at the higher doses of the combination, which will be used in Phase 3 clinical trials, 300/120mg ABT-493/ABT-530 with and without 800mg RBV. There were no grade 3 or 4 laboratory abnormalities.

Part 2 of the study is underway to examine once-daily ABT-493 (300mg) and ABT-530 (120mg) without RBV in a larger group of DAA treatment-experienced patients, including those with compensated cirrhosis and in genotypes 4-6.

About AbbVie's HCV Clinical Development Program
AbbVie's HCV clinical development program is intended to advance scientific knowledge and the clinical care of people with chronic HCV infection by investigating pan-genotypic (genotypes 1-6), all-oral, ribavirin-free, once-daily treatment for 12 weeks. An eight-week treatment duration with ABT-493 and ABT-530 will be investigated across all genotypes in our comprehensive Phase 2/Phase 3 clinical trial program, which focuses on areas of ongoing need in HCV.

AbbVie's investigational regimen includes 300mg ABT-493, an NS3/4A protease inhibitor, and 120mg ABT-530, an NS5A inhibitor.

ABT-493 was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals (NASDAQ: ENTA) for HCV protease inhibitors and regimens that include protease inhibitors.

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. Together with its wholly-owned subsidiary, Pharmacyclics, AbbVie employs more than 28,000 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.

1 Poordad, F et al. High Efficacy of ABT-493 and ABT-530 in HCV Genotype 1 Infected Patients Who Have Failed Direct-Acting Antiviral-Containing Regimens: The MAGELLAN-I Study. Oral presentation #GS11; presented at The International Liver Congress™ (ILC), the Annual Meeting of the European Association for the Study of the Liver (EASL) in Barcelona, Spain, April 13-17, 2016.

European Medicines Agency’s PRAC extends the scope of its safety review on direct-acting antivirals for hepatitis C

Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 11-14 April 2016

In April, the European Medicines Agency’s (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) started a new safety review, extended the scope of an ongoing review procedure and agreed the rules of procedure for public hearings.

PRAC reviews diabetes medicine canagliflozin

The PRAC has started a review of the diabetes medicine canagliflozin after an increase in amputations mostly affecting toes was observed in an ongoing clinical trial called CANVAS. Canagliflozin is the active substance in two centrally authorised diabetes medicines, Invokana and Vokanamet (which also contains metformin).

More information is provided in the table below.

PRAC extends the scope of its review on direct-acting antivirals for hepatitis C

The PRAC also extended the scope of its ongoing safety review of medicines known as direct-acting antivirals (Daklinza, Exviera, Harvoni, Olysio, Sovaldi, Viekirax) used for treating chronic (long-term) hepatitis C (an infectious disease that affects the liver, caused by the hepatitis C virus).

At its previous meeting in March, the Committee had initiated a review following cases of hepatitis B re-activation in patients who have been infected with hepatitis B and C viruses, and who were treated with direct-acting antivirals for hepatitis C.

In April 2016, data from a study became available regarding the risk of liver cancer (hepatocellular carcinoma) coming back in patients who were treated with these medicines. The study suggested that these patients were at risk of their cancer coming back earlier than patients with hepatitis C who were not treated with direct-acting antivirals. The scope of the ongoing review has therefore been extended to also assess the risk of liver cancer with these medicines.

More information is provided in the table below.

Rules of procedure on public hearings on selected safety reviews adopted

The PRAC has adopted the final rules of procedure for public hearings to be held by the Committee. The rules of procedure describe the process and practical arrangements for the preparation, conduct and follow-up of public hearings. Public hearings are a new tool for EMA to engage European Union (EU) citizens in the supervision of medicines and to listen to their views and experiences.

Source

More information is provided in a separate press release.

ILC2016 Coverage: Impact of Viekirax (ombitasvir/parataprevir/ritonavir and Exviera (dasabuvir) Real-world experience with 3-D regimen lives up to phase 3 studies

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Real-world experience with 3-D regimen lives up to phase 3 studies

BARCELONA — In this video perspective from the International Liver Congress 2016, Heiner Wedemeyer, MD, research group leader, department of gastroenterology, hepatology and endocrinology at Hannover Medical School in Germany, discusses his real-world experience with the German Hepatitis C-Registry. Specifically, Wedemeyer looked at the impact of Viekirax (ombitasvir/parataprevir/ritonavir, AbbVie) and Exviera (dasabuvir, AbbVie), together known as Viekira Pak in the United States, in his own practice, showing that the everyday impact is similar to that seen in phase 3 trials.

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