An all-oral phase IIa study combining Simeprevir, TMC647055 and JNJ56914845 in hepatitis C patients to be initiated

Stockholm, Sweden—Medivir AB (OMX: MVIR), announces the initiation of a phase IIa trial in chronic genotype 1 hepatitis C infected patients to evaluate the efficacy, safety and tolerability of a 12-week combination therapy of simeprevir, TMC647055 and JNJ56914845, a NS5A replication complex inhibitor.

Study design
Approximately 40 patients will be enrolled in this open-label study to assess the efficacy, safety and tolerability of the co-administration of simeprevir, TMC647055 and two different doses of JNJ56914845 without ribavirin. The trial will evaluate genotype 1a and 1b HCV-infected patients who are either treatment-naïve or who have relapsed after prior treatment with interferon and ribavirin. Patients will receive 75 mg of simeprevir, 30 or 60 mg of JNJ56914845 and 450 mg of TMC647055 plus a low dose of ritonavir as a pharmacokinetic enhancer, each once daily for 12 weeks.

For additional information about this study, please visit www.clinicaltrials.gov

For more information please contact:
Rein Piir, EVP Corporate Affairs & IR, mobile: +46 708 537 292

Medivir is required under the Securities Markets Act to make the information in this press release public. The information was submitted for publication at 08.30 a.m. CET on 12 December 2013.

About Simeprevir
Simeprevir is an NS3/4A protease inhibitor jointly developed by Medivir and Janssen R&D Ireland for the treatment of chronic hepatitis C infection in combination with other antivirals in HCV genotype 1 & 4 infected patients with compensated liver disease, including cirrhosis.

Simeprevir was approved for the treatment of genotype 1 hepatitis C in September 2013 in Japan and in the USA and Canada in November. A Marketing Authorisation Application was submitted to the European Medicines Agency (EMA) in April 2013 by Janssen-Cilag International NV seeking approval of simeprevir for the treatment of genotype 1 or genotype 4 chronic hepatitis C. To date, more than 3,700 patients have been treated with simeprevir in clinical trials.

About TMC647055
TMC647055 is a potent non-nucleoside hepatitis C polymerase inhibitor with broad genotypic coverage. TMC647055 is in phase II clinical development and is developed by Janssen R&D Ireland to treat chronic hepatitis C virus infections. TMC647055 is being investigated in combination with other DAA agents in all oral interferon-free regimens. There have been no treatment-emergent serious adverse events reported in the program.

About JNJ56914845
JNJ56914845, is a potent NS5A replication complex inhibitor. To date phase I and phase II clinical studies conducted demonstrated that JNJ56914845 60 mg once daily is well tolerated and produces rapid, substantial decreases in HCV RNA in treatment-naïve CHC subjects when given alone as a single dose and for 4 weeks in combination with pegIFN and RBV.     

About Medivir
Medivir is an emerging research-based pharmaceutical company focused on infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company’s key asset is simeprevir, a novel protease inhibitor for the treatment of hepatitis C that is being developed in collaboration with Janssen R&D Ireland. The company is also working with research and development in other areas, such as bone disorders and neuropathic pain. Medivir has also a broad product portfolio with prescription pharmaceuticals in the Nordics.

For more information about Medivir AB, please visit the Company’s website: www.medivir.com

Source

HELIX-2, a phase II all-oral combination study of Simeprevir, TMC647055 and Samatasvir (IDX719) for the treatment of hepatitis C has been initiated

02-Dec-13 12:15

Stockholm, Sweden—Medivir AB (OMX: MVIR), announces that IDENIX has initiated a phase II clinical trial (HELIX-2) evaluating an all-oral, direct-acting antiviral (DAA) HCV combination regimen of simeprevir, samatasvir and TMC647055 with a pharmacokinetic enhancer.

The HELIX-2 trial is a 12-week, randomized, open-label study evaluating the efficacy, safety and tolerability of simeprevir, TMC647055 and samatasvir. The trial will evaluate genotype 1 HCV-infected patients who are either treatment-naïve or who have relapsed after prior treatment with interferon and ribavirin. Patients will receive 75 mg of simeprevir, 50 mg samatasvir and 450 mg of TMC647055 plus a low dose of ritonavir as a pharmacokinetic enhancer, each once daily for 12 weeks, with or without the addition of ribavirin.

The HELIX-2 trial is the second study in HCV-infected patients to commence under a non-exclusive collaboration agreement between Idenix and Janssen established in January 2013. The HELIX-1 trial of samatasvir in combination with simeprevir was initiated in May 2013 and is ongoing.

For additional information about this study, please visit www.clinicaltrials.gov

For more information please contact:
Rein Piir, EVP Corporate Affairs & IR, mobile: +46 708 537 292

About Simeprevir
Simeprevir is an NS3/4A protease inhibitor jointly developed by Medivir and Janssen R&D Ireland for the treatment of chronic hepatitis C infection in combination with other antivirals in HCV genotype 1 & 4 infected subjects with compensated liver disease, including cirrhosis.

Simeprevir was approved for the treatment of genotype 1 hepatitis C in September 2013 in Japan and in the USA and Canada in November. A Marketing Authorisation Application was submitted to the European Medicines Agency (EMA) in April 2013 by Janssen-Cilag International NV seeking approval of simeprevir for the treatment of genotype 1 or genotype 4 chronic hepatitis C. To date, more than 3,700 patients have been treated with simeprevir in clinical trials.

About TMC647055
TMC647055 is a potent non-nucleoside hepatitis C polymerase inhibitor with broad genotypic coverage. TMC647055 is in phase II clinical development and is developed by Janssen R&D Ireland to treat chronic hepatitis C virus infections. TMC647055 is being investigated in combination with other DAA agents in all oral interferon-free regimens. There have been no treatment-emergent serious adverse events reported in the program.

About Samatasvir (IDX719)
Samatasvir is an NS5A inhibitor with low picomolar, pan-genotypic antiviral activity in vitro. To date, samatasvir has been safe and well-tolerated after single and multiple doses of up to 150 mg in healthy volunteers up to 14 days duration, and in HCV-infected patients up to 12 weeks duration. There have been no treatment-emergent serious adverse events reported in the program. Samatasvir has demonstrated potent pan-genotypic antiviral activity in HCV-infected patients with mean maximal viral load reductions up to approximately 4.0 log10 IU/mL across HCV genotypes 1-4 in a proof-of-concept, three-day monotherapy study.

About Medivir
Medivir is an emerging research-based pharmaceutical company focused on infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company’s key pipeline asset is simeprevir, a novel protease inhibitor for the treatment of hepatitis C that is being developed in collaboration with Janssen R&D Ireland. The company is also working with research and development in other areas, such as bone disorders and neuropathic pain. Medivir has also a broad product portfolio with prescription pharmaceuticals in the Nordics.

For more information about Medivir AB, please visit the Company’s website: www.medivir.com

Medivir is a collaborative and agile pharmaceutical company with an R&D focus on infectious diseases and a leading position in hepatitis C. We are passionate and uncompromising in our mission to develop and commercialize innovative pharmaceuticals that improve people’s health and quality of life.

Source

Janssen Acquires Investigational NS5A Inhibitor for the Treatment of Hepatitis C from GlaxoSmithKline

TITUSVILLE, N.J., Oct. 8, 2013 /PRNewswire/ -- Janssen Pharmaceuticals, Inc. (Janssen) announced today the acquisition of the investigational compound GSK2336805, an NS5a replication complex inhibitor in Phase 2 development for the treatment of chronic hepatitis C, from an affiliate of GlaxoSmithKline plc. Janssen has acquired all rights to develop and commercialize GSK2336805, including in combination with other drugs. Financial details of the agreement have not been disclosed.

Janssen plans to initiate Phase 2 studies to evaluate the use of GSK2336805 in interferon-free combinations with the investigational protease inhibitor simeprevir (TMC435) and TMC647055, Janssen's non-nucleoside polymerase inhibitor, for the treatment of chronic hepatitis C in adult patients with compensated liver disease.

"We're excited to add GSK2336805 to our existing portfolio of direct-acting antivirals (DAAs). This addition will broaden our clinical development program as we continue to look for new investigational interferon-free treatment combinations to combat the hepatitis C virus," said Gaston Picchio, Hepatitis Disease Area Leader, Janssen. "Janssen is dedicated to working with the hepatitis C community to investigate our portfolio of DAAs in a number of different treatment combinations and hepatitis C patient populations."  

About GSK2336805
GSK2336805 is an investigational once-daily NS5a replication complex inhibitor in Phase 2 development for the treatment of chronic hepatitis C in adult patients with compensated liver disease, including all stages of liver fibrosis.

About Simeprevir
Simeprevir is an investigational NS3/4A protease inhibitor jointly developed by Janssen R&D Ireland and Medivir AB for the treatment of genotype 1 and genotype 4 chronic hepatitis C in adult patients with compensated liver disease, including all stages of liver fibrosis. Simeprevir works by blocking the protease enzyme that enables the hepatitis C virus to replicate in host cells.

Janssen is responsible for the global clinical development of simeprevir and has acquired exclusive, worldwide marketing rights, except in the Nordic countries. Medivir will retain marketing rights for simeprevir in these countries. Simeprevir has been submitted for regulatory approval in the United States, Canada and Europe, and was approved in September 2013 in Japan. To date, more than 3,700 patients have been treated with simeprevir in clinical trials.

Additionally, simeprevir is being studied in combination with several DAAs with different mechanisms of action, with and without ribavirin, as part of interferon-free regimens. These include:

• The Phase 2 COSMOS study of simeprevir and Gilead's nucleotide inhibitor sofosbuvir (GS-7977) in treatment-naive and previous null-responder genotype 1 hepatitis C patients, including patients with cirrhosis; 
• A Phase 2 study of simeprevir and Bristol-Myers Squibb's NS5A replication complex inhibitor daclatasvir in treatment-naive and previous null-responder genotype 1 hepatitis C patients;  and
• The Phase 2 HELIX-1 study of simeprevir and Idenix's once-daily pan-genotypic NS5A inhibitor samatasvir (IDX719) in treatment-naive genotype 1b and genotype 4 hepatitis C patients.

For additional information about simeprevir, please visit www.clinicaltrials.gov.

About Hepatitis C
Hepatitis C, a blood-borne infectious disease of the liver and a leading cause of chronic liver disease, is the focus of a rapidly evolving treatment landscape. Approximately 150 million people are infected with hepatitis C worldwide – including approximately 3.2 million people in the United States – and 350,000 people per year die from the disease globally. When left untreated, hepatitis C can cause significant damage to the liver including cirrhosis. Additionally, hepatitis C may increase the risk of developing complications from cirrhosis, which may include liver failure.

About Janssen
At Janssen, we are dedicated to addressing and solving some of the most important unmet medical needs of our time in infectious diseases and vaccines, oncology, immunology, neuroscience, and cardiovascular and metabolic diseases. Driven by our commitment to patients, we develop innovative products, services and healthcare solutions to help people throughout the world. Janssen Pharmaceuticals, Inc. and Janssen R&D Ireland are part of the Janssen Pharmaceutical Companies of Johnson & Johnson. Please visit http://www.janssenrnd.com for more information.

(This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995.  The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events.  If underlying assumptions prove inaccurate or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Pharmaceuticals, Inc., any of the other Janssen Pharmaceutical Companies and/or Johnson & Johnson.  Risks and uncertainties include, but are not limited to, general industry conditions and competition; economic factors, such as interest rate and currency exchange rate fluctuations; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approvals; challenges to patents; impact of business combinations; changes in behavior and spending patterns or financial distress of purchasers of health care products and services; changes to governmental laws and regulations and domestic and foreign health care reforms; trends toward health care cost containment; and increased scrutiny of the health care industry by government agencies.  A further list and description of these risks, uncertainties and other factors can be found in Exhibit 99 of Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended December 30, 2012.  Copies of this Form 10-K, as well as subsequent filings, are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson.  None of the Janssen Pharmaceutical Companies nor Johnson & Johnson undertake to update any forward-looking statements as a result of new information or future events or developments.)

Media Contact: Daniel De Schryver 
Mobile: +49 173 76 89 149

Media Contact: Craig Stoltz 
Mobile: +1 (215) 325-3612

Investor Contact: Stan Panasewicz
Office: +1 (732) 524-2524

Investor Contact: Louise Mehrotra
Office: +1 (732) 524-6491

SOURCE Janssen Pharmaceuticals, Inc.

RELATED LINKS
http://www.janssenrnd.com

Source

Janssen HCV Drug Research & Development

Provided by NATAP

Reported by Jules Levin

In the Spring Janssen & Gilead submitted New Drug Applications to the FDA requesting approval. The FDA hearing appears to be scheduled for Oct 24-25.

A Study of the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of JNJ-47910382 at Different Doses and Dose Regimens in Asian Genotype-1, Chronic, HCV-Infected Patients

Study in HCV-Infected Patients to Determine the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of JNJ-47910382

A Study in Healthy Participants Investigating the Safety, Tolerability and Plasma Pharmacokinetics (PK) of Single Oral Doses of JNJ-47910382

IDX719 in Combination With Simeprevir and Ribavirin for 12 Weeks in Subjects With Chronic Hepatitis C Infection
http://www.clinicaltrials.gov/ct2/show/NCT01852604?term=Janssen+AND+Hepatitis+C&recr=Open&no_unk=Y&rank=9

Antiviral Drugs Advisory Committee .........October 24-25
http://www.fda.gov/AdvisoryCommittees/Calendar/ucm153468.htm

Simeprevir (TMC435) with peginterferon/ribavirin for chronic hCV genotype 1 infection in treatment-naïve patients: results from QUEST-1, a Phase III trial
http://www.natap.org/2013/EASL/EASL_10.htm

Simeprevir (TMC435) with peginterferon-α2a or -α2b and ribavirin in treatment-naïve HCV genotype 1 patients: QUEST-2, a randomised Phase III trial
http://www.natap.org/2013/EASL/EASL_18.htm

Simeprevir with Peginterferon/ribavirin for Treatment of Chronic HCV Genotype 1 Infection in Patients Who Relapsed After Previous Interferon-based Therapy: Results from PROMISE, a Phase III Trial
http://www.natap.org/2013/DDW/DDW_06.htm

COSMOS Study: SVR4 results of a once daily regimen of simeprevir (TMC435) plus sofosbuvir (GS-7977) with or without ribavirin in HCV genotype 1 null responders
http://www.natap.org/2013/CROI/croi_34.htm

Medivir Press Release: New Drug Application has been filed with FDA for Simeprevir (TMC435) for combination treatment of adult patients with genotype 1 chronic hepatitis C
http://www.natap.org/2013/HCV/040213_01.htm

Idenix Pharmaceuticals Announces Initiation of Phase II All-Oral Combination Study of Samatasvir (IDX719) and Simeprevir (TMC435) for the Treatment of Hepatitis C Virus (HCV) Infection
http://www.natap.org/2013/HCV/060213_04.htm

Combination Therapy of TMC647055 With Simeprevir (TMC435) in Genotype 1 HCV Patients
http://www.natap.org/2013/EASL/EASL_41.htm

TMC055 Monotherapy data:
Human safety, pharmacokinetics and antiviral activity of TMC647055, a novel HCV non-nucleoside polymerase inhibitor....... http://www.natap.org/2011/AASLD/AASLD_04.htm

Here is the link to the study on clinical trials.gov where you can see low dose 30mg RTV is used:
A Study to Evaluate the Safety, Tolerability, and Effectiveness of a 12-Week Combination Therapy of TMC647055 and TMC435 With a Pharmacokinetic Enhancer With and Without Ribavirin in Chronic Genotype-1 Hepatitis C Infected Patients.......http://clinicaltrials.gov/ct2/show/NCT01724086?term=tmc647055&rank=3

EASL: Combination Therapy of TMC647055 With Simeprevir (TMC435) in Genotype 1 HCV Patients - (04/30/13)

2nd generation NS5As

In Vitro Resistance Analysis of Merck's HCV NS5a Inhibitor MK-8742 Demonstrates Increased Potency AgainstClinical Resistance Variants and Improved Resistance Profile
http://www.natap.org/2012/EASL/EASL_46.htm

GS-5816, a Second-Generation HCV NS5A Inhibitor With Potent Antiviral Activity, Broad Genotypic Coverage, and a High Resistance Barrier
http://www.natap.org/2013/EASL/EASL_34.htm

Healthy Volunteer First-in-Human Evaluation of GS-5816, a Novel Second Generation Broad-Genotypic NS5A Inhibitor With Potential for Once-Daily Dosing - (04/29/13)

ACH-3102, A Second Generation NS5A Inhibitor, Demonstrates Potent Antiviral Activity in Patients with Genotype 1A HCV Infection Despite the Presence of Baseline NS5A-Resistant Variants - (05/09/13)

FINDINGS FROM CLINICAL VIROLOGY STUDIES ON ACH-3102 ARE CONSISTENT WITH PRECLINICAL OBSERVATIONS ON ITS IMPROVED POTENCY AGAINST GENOTYPE-1A HCV AND RESISTANT VARIANTS - (05/09/13)

No Clinically Significant Pharmacokinetic Interaction Between Sovaprevir and ACH-3102 in Healthy Volunteers - (05/09/13)

Synergistic Interactions of HCV NS5A Replication Complex Inhibitors Sensitize Resistant Variants and Enhance the Efficacy of Daclatasvir (DCV, BMS-790052) In Vitro and In Vivo - (04/27/13)

PRECLINICAL CHARACTERISTICS OF ACH-3102: A NOVEL HCV NS5A INHIBITOR WITH IMPROVED POTENCY AGAINST GENOTYPE-1A VIRUS AND VARIANTS RESISTANT TO 1ST GENERATION NS5A INHIBITORS
http://www.natap.org/2012/EASL/EASL_79.htm

Source

A Phase IIa Interferon Free Combination Hepatitis C Trial of Simeprevir (TMC435) and TMC647055 Will Commence Shortly

Published: September 20, 2012

STOCKHOLM, September 20, 2012 - /PRNewswire/ --
Medivir AB (OMX: MVIR), announced today that simeprevir (TMC435) and TMC647055, a non-nucleoside inhibitor (NNI) will enter a phase IIa interferon free combination trial.

Simeprevir is a once daily potent HCV NS3/4A protease inhibitor in phase III clinical development for the treatment of chronic hepatitis C jointly developed by Medivir and Janssen Research & Development Ireland (Janssen). TMC647055 is a potent NNI (non-nucleoside inhibitor) of the HCV NS5B polymerase and is being developed by Janssen R&D.

"This study is in line with Medivir's and Janssen's strategy to evaluate different combination possibilities with simeprevir for interferon-free HCV treatments. This will broaden our understanding of simeprevir, which we believe has the necessary characteristics to potentially become a key component of future hepatitis C treatment regimens, including combination with interferon and ribavirin as well as interferon-free therapies," comments Charlotte Edenius, Medivir's EVP of Research and Development.

Study design

This will be an open label study in patients who are chronically infected with HCV genotype-1a or 1b to assess the efficacy, safety and tolerability of the combination. The primary endpoint in the study will be SVR12 (sustained virologic response 12 weeks after end of treatment). Simeprevir, TMC647055 and low-dose ritonavir will be co-administered once daily, with and without ribavirin.

Approximately 40 patients will be enrolled in this study, which is divided in two parts. The first part will include patients chronically infected with HCV genotype-1, who are either treatment-naive or have relapsed after prior pegylated interferon (PegIFN)/ribavirin treatment. The treatment will consist of simeprevir, TMC647055 and low-dose ritonavir, with and without ribavirin for 12 weeks.

The second part of the trial will investigate the same regimen in prior null responder patients chronically infected with HCV genotype 1a.

Recruiting: TMC435HPC3001 - An Efficacy, Safety and Tolerability Study for TMC435 vs Telaprevir in Combination With PegINFα-2a and Ribavirin in Chronic Hepatitis C Patients Who Were Null or Partial Responders to Prior PegINFα-2a and Ribavirin Therapy

Not yet recruiting: Study of Daclatasvir and TMC435 for Subjects With Genotype 1 Chronic Hepatitis C

Completed: TMC647055HPC1001 - First-in-human Trial to Examine Safety, Tolerability and Pharmacokinetics (How the Drug is Absorbed Into the Bloodstream) of Increasing Single Oral Doses and of Increasing Repeated Oral Doses of TMC647055 in Healthy Volunteers and in Hepatitis C Virus Infected Patients

Medivir acquires preclinical antiviral programs including hepatitis C and prodrug technologies - press release

05-Sep-12 Stockholm, Sweden-

Medivir announced today that it has acquired preclinical research stage assets from Novadex Pharmaceuticals AB.

The acquisition includes intellectual property and prodrug technologies in order to further strengthen Medivir's hepatitis C platform and know how.

The acquired portfolio of research stage antiviral programs includes novel nucleotide polymerase inhibitors that have been identified and developed. It also includes prodrug technologies which could be applied to both protease inhibitors and nucleoside analogues to enhance their overall pharmacokinetic properties.

"We are very pleased to be able to make these additions to the Medivir R&D portfolio, which will further strengthen our pipeline and capabilities in the antiviral disease area. There are several synergies with the Medivir anti-viral projects and prodrug approaches which we aim to explore" comments Charlotte Edenius, Medivir's EVP of Research and Development .

The transaction value, which consists of up-front payment as well as future potential milestone payments, is not disclosed.

Source