HCV-TARGET - FDA, academia and industry team up to end hepatitis C

FDA, academia and industry team up to end hepatitis C

Published: August 29th, 2013

Category: Health, Research

GAINESVILLE, Fla. — As doctors prepare to manage an influx of new hepatitis C patients and treatment options, a collaboration among academia, industry and the U.S. Food and Drug Administration is poised to deliver real-world data that can help doctors and patients optimize their treatment experience.

A research consortium known as the Hepatitis C Therapeutic Registry and Research Network, or HCV-TARGET, has joined forces with the FDA to share national data on how newly approved therapies for hepatitis C are used and managed in routine practice. HCV-TARGET is led jointly by investigators at the University of Florida and the University of North Carolina at Chapel Hill and is sponsored in part by multiple pharmaceutical companies.

The new partnership’s goal is to establish research collaborations using the HCV-TARGET database to better inform patients and clinicians about hepatitis C therapies.

“This collaboration will not only strengthen our ongoing efforts to monitor the safety and effectiveness of existing hepatitis C treatment regimens,” said Dr. Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, “it will also provide opportunities for FDA scientists to apply their research expertise in studying existing data held by HCV-TARGET to identify areas for improvement in clinical trial design that may help improve the future of HCV drug development programs.”

Hepatitis C is a viral liver disease that can lead to liver damage, cirrhosis, liver failure or liver cancer. It is transmitted through contact with infected blood. Because a person with chronic hepatitis C can live symptom-free for decades, many people do not know they are infected.

Two factors increase the significance of this collaboration:
More patients to be screened and treated — Within the last year, both the Centers for Disease Control and Prevention and the U.S. Preventive Services Task Force recommended all baby boomers be tested for hepatitis C. The CDC estimates baby boomers represent three-quarters of the more than 3 million Americans believed to be infected with hepatitis C. Among those at highest risk are individuals who received blood transfusions before 1992, when screening donated blood for the virus began.

New treatments on the horizon — The first all-oral hepatitis C treatment is moving through the final stages of FDA approval. If approved, it would be the first of a new generation of hepatitis C drugs that will improve what for many has been a grueling treatment regimen that can take up to 48 weeks and requires injections of interferon, a drug that can be difficult to tolerate. The introduction of new drugs will bring new questions about managing side effects, drug combinations and other clinical considerations.

“Leading liver doctors across the country have joined HCV-TARGET to study and navigate rapidly evolving treatment paradigms for hepatitis C. We see a healthier future for patients battling this virus and formed HCV-TARGET to help guide the way,” said Dr. David R. Nelson, co-principal investigator, director of the UF Clinical and Translational Science Institute and a professor of medicine at UF Health, which serves as the clinical coordinating center for HCV-TARGET.

Following close to 2,500 patients in North America who have agreed to participate in its study to date, HCV-TARGET includes populations underrepresented in clinical trials such as patients with cirrhosis, patients age 65 and older and African-Americans. The initial focus of the network’s observational study has been treatment with boceprevir and telaprevir, drugs newly approved by the FDA when HCV-TARGET launched in 2011. HCV-TARGET will expand its study this year to include the entire spectrum of antiviral hepatitis C therapeutics.

“Real-world data about how drugs perform outside of restricted clinical trials are extremely important. HCV-TARGET allows us to capture this information using novel approaches to ensure the integrity and quality of the data. Through our partnership with the FDA, we hope this information can be used to help doctors and their patients more readily determine the most beneficial treatment options across a broad spectrum of patients,” said Dr. Michael W. Fried, co-principal investigator and professor of medicine at the UNC School of Medicine, which serves as the HCV-TARGET data coordinating center.

HCV-TARGET and the FDA signed in May a memorandum of understanding to promote scientific research in the area of hepatitis C drug development. In mid-July, HCV-TARGET held meetings with representatives from the FDA Center for Drug Evaluation and Research’s division of antiviral products and offices of computational science, clinical pharmacology and biostatistics. Attendees agreed one of the first priorities should be to align how data elements of common interest are defined so the clinical trial data collected by the FDA can be reasonably compared to the real-world observational data collected by HCV-TARGET, a critical step in developing research collaborations and pilot projects. In addition, the agreement allows an FDA representative to join HCV-TARGET’s advisory council.

HCV-TARGET includes 103 academic and community sites in 31 states, Puerto Rico, Canada and Europe. HCV-TARGET currently receives ongoing industry support from Merck, Genentech, Kadmon and Vertex. Fried receives research grant support from and serves as ad hoc consultant to Genentech, Vertex, Merck, Gilead, Bristol Myers Squibb, Janssen Pharmaceuticals and Abbott. Nelson receives grant support from Genentech, Kadmon, Merck, Vertex, Gilead, Boehringer Ingelheim and Abbott/Abbvie; and payment for the development of educational presentations from Clinical Care Options, Rush University Medical Center, Practice Point Communications and the Chronic Liver Disease Foundation.

CreditsMedia ContactClaire Baralt (UF), cbaralt@ufl.edu, 352-273-8211Media ContactMichelle Maclay (UNC), maclay@med.unc.edu, 919-843-5365

http://news.ufl.edu/2013/08/29/hcv-target-2/

Healio: Frequent coffee, chocolate consumption reduced liver enzymes in HIV/HCV coinfected patients

Frequent coffee, chocolate consumption reduced liver enzymes in HIV/HCV coinfected patients

Carrieri MP. J Hepatol. 2013;doi:10.1016/j.jhep.2013.08.014.

August 29, 2013

Patients coinfected with HIV and HCV who reported eating chocolate daily and drinking three or more cups of coffee a day had lower levels of ALT and AST than those who consumed fewer polyphenol-rich foods in a recent study.

Researchers evaluated data collected from 990 adult patients coinfected with HCV and HIV enrolled in the ANRS CO13 HEPAVIH prospective cohort study. Patients with cirrhosis had follow-up visits every 6 months, while noncirrhotic participants had annual visits, with liver biochemistry assessed at each visit. Participants also responded to annual self-administered questionnaires regarding sociodemographic status and dietary and drug habits.
Continue reading...

Interferon-free regimen shows promise for patients with chronic HCV
August 29, 2013
A 24-week interferon-free regimen of sofosbuvir and ribavirin resulted in a high sustained virologic response rate among hepatitis C virus patients with unfavorable treatment characteristics, according to study results published in JAMA.

"This is another important step toward the realization that direct-acting agents in an interferon-free regimen will transform the field of the treatment of chronic hepatitis C virus," study researcher Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, told Infectious Disease News.
Continue reading..

Besifovir noninferior to entecavir for chronic HBV in phase 2b trial

Lai CL. Gut. 2013;doi:10.1136/gutjnl-2013-305138.

August 28, 2013
Patients with chronic hepatitis B treated with besifovir experienced similar outcomes to entecavir recipients, but often required carnitine supplementation, in a recent study.
Continue reading...

New protease inhibitors showing promise for HIV/HCV coinfection
August 28, 2013
This is an exciting time in the treatment of chronic hepatitis C virus infections. As opposed to the antibiotic pipeline, there are a number of new antiviral agents for treatment of hepatitis C in development that may transform the way these patients are treated.
Continue reading...
 

Medivir- Interim Results Simeprevir and Sofosbuvir in HCV Patients with METAVIR Scores F3-F4

Medivir Announces Interim Results from Cohort 2 of the COSMOS Study Evaluating Simeprevir and Sofosbuvir in HCV Patients with METAVIR Scores F3-F4 

In Hepatitis C patients with advanced liver fibrosis or cirrhosis (METAVIR F3 or F4) 12 weeks all oral treatment with simeprevir and sofosbuvir with or without ribavirin led to SVR4 rates of 96% and 100%, respectively
Once-daily simeprevir and sofosbuvir with or without ribavirin was generally safe and well tolerated

STOCKHOLM--(BUSINESS WIRE)-- Regulatory news:

Medivir AB (OMX: MVIR) (STO:MVIR-B) today announced interim results from the second Cohort in the ongoing COSMOS study evaluating a once daily combination of simeprevir and sofosbuvir in hard to cure hepatitis C (HCV) patients.

SVR4 results from the 12 week arms of Cohort 2, including treatment naïve or previous null responder HCV patients all with METAVIR score F3-F4 were reported. Treatment for 12 weeks with simeprevir and sofosbuvir, with or without ribavirin, led to SVR4 rates of 96% and 100%, respectively.

Interim results from Cohort 1 of the COSMOS study, which include only prior null responder HCV patients (METAVIR F0-F2) have been reported earlier and demonstrated SVR8 rates of 96% and 93% after 12 weeks treatment simeprevir and sofosbuvir with and without ribavirin, respectively.

“The high SVR rates seen in genotype 1 prior null responders and treatment-naïve patients with advanced liver disease, in the COSMOS study and the safety profile of the combination are highly encouraging. We look forward to the final results of this study in difficult to cure patients.” says Charlotte Edenius, EVP Development, Medivir AB.

COSMOS - Study Design

COSMOS is a randomized, open label, phase IIa clinical trial evaluating a once-daily combination of the HCV protease inhibitor simeprevir and the nucleotide sofosbuvir with and without ribavirin (RBV) for 12 and 24 weeks. Cohort 1 (n=80) evaluates prior null responder genotype 1 hepatitis C (HCV) patients with METAVIR scores F0-F2 and Cohort 2 (n=87) evaluates prior null responder and treatment-naïve genotype 1 hepatitis C patients with METAVIR scores F3-F4. The METAVIR score is used to quantify the degree of inflammation and fibrosis of the liver. Liver fibrosis is scored on a four-point scale.

At the time of the interim analysis, SVR4 results were available for all patients (n=41) in the 12 week arms of Cohort 2. In this Cohort, 78.2% of patients had GT1a subtype with 40% of those having a Q80K baseline polymorphism, 79.3% had IL28B CT or TT genotype, 47.1% had Metavir score F4 (cirrhosis) and 54.0% were prior null responders.

In the previously reported Cohort 1, 77.5% of the patients had GT1a subtype with 50% of those having a Q80K baseline polymorphism, 93.7%, had IL28B CT or TT genotype and 58.8% had METAVIR score F2.

COSMOS - Summary Interim Results: Efficacy

Efficacy results with 150 mg simeprevir (SMV) and 400 mg sofosbuvir (SOF) once daily for 12 weeks with or without ribavirin (RBV). Intent-to-treat (ITT) population.
Cohort 1* Cohort 2

Prior null responder HCV patients
(METAVIR score F0-F2)

		Cohort 1*				Cohort 2
		Prior null responder HCV patients (METAVIR score F0-F2)				Prior null responder and treatment naïve HCV patients (METAVIR scores F3 or F4)
		SMV / SOF+ RBV (n=27)		SMV / SOF (n=14)		SMV / SOF + RBV (n=27)		SMV / SOF(n=14)
SVR4		26/27(96%)		13/14(93%)		26/27(96%)		14/14(100%)
SVR8		26/27(96%)		13/14(93%)		-		-

* Data reported at the 20th Conference on Retroviruses and Opportunistic Infections (CROI) in March 2013 in Atlanta, USA. SVR: Sustained Virologic Response 4 or 8 weeks (SVR4 or SVR8) after end of treatment.

There were no viral breakthroughs in either Cohort. At the time of respective cut-off there was 1 relapse in Cohort 2, which was detected 4 weeks after end of treatment. As previously reported there were 2 relapses detected in Cohort 1 both at the 4 week time point after end of treatment.

COSMOS - Summary Interim Results: Safety

Once-daily simeprevir and sofosbuvir with or without ribavirin for 12 weeks was generally considered safe and well tolerated. Among events defined in the protocol as being of special interest, increased bilirubin was observed in 9.3% of the patients in the ribavirin containing arms, compared with 0%, for the non-ribavirin containing arms. Anemia was observed in 13.0% of the patients in the ribavirin containing arms, compared with 0% for the non-ribavirin containing arms.

About Simeprevir

Simeprevir is a new generation NS3/4A protease inhibitor jointly developed by Medivir and Janssen R&D Ireland, part of the Janssen Pharmaceutical Companies for the treatment of chronic hepatitis C in adult patients with compensated liver disease.

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

About Sofosbuvir

Sofosbuvir (formerly referred to as GS-7977) is a once-daily nucleotide analog polymerase inhibitor for the treatment of HCV infection being developed by Gilead Sciences, Inc. Sofosbuvir is being evaluated as part of multiple therapeutic regimens, including programs with RBV alone and in combination with peg-IFN and RBV.

About Hepatitis C

Hepatitis C, a blood-borne infectious disease of the liver and a leading cause of chronic liver disease and liver transplants, is a rapidly evolving treatment area with a clear need for innovative treatments. Approximately 150 million people are infected with hepatitis C worldwide, and 350,000 people per year die from the disease.

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 in late phase III clinical development for hepatitis C that is being developed in collaboration with Janssen R&D Ireland. 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

This information was brought to you by Cision http://news.cision.com

Gilead's Sofosbuvir and Ribavirin for Hepatitis C Genotype 1 shows promise in NIH trial

Investigational oral regimen for hepatitis C shows promise in NIH trial

Side effects minimized with combination therapy in hard-to-treat patients

The new study also differs from many previous trials because it enrolled people with severe liver damage as well as those with mild or moderately scarred livers.

In a study of an all-oral drug regimen, a majority of volunteers with liver damage due to hepatitis C virus (HCV) infection were cured following a six-month course of therapy that combined an experimental drug, sofosbuvir, with the licensed antiviral drug ribavirin. The results showed that the regimen was highly effective in clearing the virus and well tolerated in a group of patients who historically have had unfavorable prognoses.

Scientists from the National Institute of Allergy and Infectious Diseases (NIAID) and the NIH Clinical Center, parts of the National Institutes of Health, led the Phase II trial. The findings appear in the Aug. 28 issue of the Journal of the American Medical Association (JAMA).

More than 3 million Americans have chronic HCV infection, a condition that is a major cause of cirrhosis (liver tissue scarring) and liver cancer, and a leading reason for liver transplantation. Deaths from HCV-related liver disease number about 15,000 every year. Standard treatment for HCV can last up to a year and usually involves weekly injections of pegylated interferon-alpha given with the oral drug ribavirin and an HCV protease inhibitor. Side effects from this treatment can be severe, notably from interferon-alpha, and can include depression, flu-like symptoms and anemia.

“There is a pressing need for hepatitis C virus treatments that are less burdensome to the patient, have fewer side effects and take less time to complete. Building on previous work, this trial provides compelling evidence that interferon-free regimens can be safe and effective,” said NIAID Director and study co-author Anthony S. Fauci, M.D.

The current study involved 60 volunteers with genotype-1 HCV, which tends to be less responsive to interferon-based treatment. Fifty of the 60 participants were African-American.

“While African-Americans make up about 13 percent of the U.S. population, they represent more than 22 percent of people with chronic HCV infection and, compared to whites, have lower cure rates with traditional HCV therapy,” said NIAID researcher Shyam Kottilil, M.D., Ph.D., the principal investigator of the trial. “Several recently completed trials testing interferon-free regimens have yielded promising results, but most volunteers in those studies were white.”

The new study also differs from many previous trials because it enrolled people with severe liver damage as well as those with mild or moderately scarred livers.

The study was divided into two parts. The first part enrolled 10 people with mild or moderate liver fibrosis. Volunteers received oral ribavirin at a dosage based on their weight along with the experimental drug sofosbuvir, also in pill form, taken daily for six months. Gilead Sciences, Inc., of Foster City, Calif., manufactures sofosbuvir and supplied it to the study physicians.

Nine volunteers completed the course of therapy. Virus was undetectable in all nine volunteers 12 weeks after the end of therapy and continued undetectable when they were tested again 24 weeks after finishing therapy. HCV does not integrate itself into human DNA. If the virus cannot be detected for a period of 12 weeks after stopping therapy, the patient is considered cured, Dr. Kottilil said.

The second part of the trial enrolled 50 volunteers, 13 of whom had liver damage rated as serious. Twenty-five received ribavirin based on their weight, and 25 received a low dose (600 milligrams per day). All received sofosbuvir.

“Because ribavirin can cause serious side effects, including anemia, we wanted to compare response rates in patients taking low-dose ribavirin with results from patients on a weight-based dosage,” said Dr. Kottilil.

At four, 12 and 24 weeks after the end of treatment, volunteers were tested for the presence of HCV. HCV levels were undetectable in 24 of the volunteers in the weight-based arm when treatment ended. Of those, 17 continued to have undetectable virus levels 24 weeks later and were considered cured of infection. In the low-dose arm, three volunteers dropped out of the study. Of the remaining 22, all responded to the treatment, but only 12 were considered cured at 24 weeks after the end of treatment.

“We saw an overall cure rate of about 70 percent using regimens that did not include interferon,” said Dr. Kottilil. “This is an encouraging result, especially considering the proportion of volunteers who had characteristics — such as being male, having HCV genotype-1 infection, being African-American and having advanced liver damage — that are recognized as predictors of poor response to treatment.”

Additional trials are underway to further determine if regimens without interferon or ribavirin can help people with chronic HCV infection, particularly those who have both HIV and HCV infections said Dr. Kottilil. These trials include two studies in which volunteers with or without HIV infection take a combination of HCV drugs (but no interferon or ribavirin) for periods of three months or less. Information about these trials is available at clinicaltrials.gov using the identifiers NCT01805882 and NCT01878799.

Further information about the HCV trial described in the current issue of JAMA is available at clinicaltrials.gov using the trial identifier NCT01441180.

NIAID conducts and supports research — at NIH, throughout the United States, and worldwide — to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website at http://www.niaid.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

NIH...Turning Discovery Into Health®

Reference
A Osinusi et al. Sofosbuvir and ribavirin for hepatitis C genotype 1 in patients with unfavorable treatment characteristics: A randomized clinical trial. JAMA DOI: 10.1001/JAMA.2013.109309
(2013).

Related -
Sofosbuvir combo effective in unresponsive HCV
A 6-month course of the antiviral drug sofosbuvir plus low-dose ribavirin was effective against chronic hepatitis C type 1 in a phase II study predominantly involving patients who had unfavorable predictors of treatment response.

Sofosbuvir plus ribavirin combo promising for hard-to-treat hep C

Last Updated: 2013-08-27 17:58:11 -0400 (Reuters Health)

By Megan Brooks

NEW YORK (Reuters Health) - In a mid-stage trial in patients with chronic hepatitis C virus (HCV)-1 and unfavorable treatment characteristics, the all-oral interferon-free regimen of sofosbuvir and ribavirin produced a high sustained virologic response (SVR) rate, researchers report.

Sofosbuvir (Gilead Sciences) is an experimental nucleotide analogue that inhibits HCV replication. It was granted priority review designation by the U.S. Food and Drug Administration in June.

Interferon-Free Combo Controls Hep C Virus
A 24-week regimen of sofosbuvir in tandem with weight-based or low-dose ribavirin was associated with a sustained virologic response to treatment of 68% and 48%, respectively, in those with a "high prevalence of unfavorable traditional predictors of treatment response," according to hyamasundaran Kottilil, MD, PhD, of the National Institute of Allergy and Infectious Diseases in Bethesda, Md., and colleagues.

Full Text Available @ NATAP
Sofosbuvir and Ribavirin for Hepatitis C Genotype 1 in Patients With Unfavorable Treatment Characteristics:  A Randomized Clinical Trial

Hepatitis C-Miravirsen: Santaris Pharma A/S Completes Enrollment in Phase 2 Clinical Trial

Also See Updates On The Website
Sept 2013 - Miravirsen: Antisense therapy for hepatitis C
COMMENTARY ON: Treatment of HCV infection by targeting microRNA

Santaris Pharma A/S Completes Enrollment in Phase 2 Clinical Trial of Miravirsen

Santaris Pharma Miravirsen SPC3649-207-205 Enrollment.pdf

Santaris Pharma A/S Completes Enrollment in Phase 2 Clinical Trial of Miravirsen In Null Responders to Pegylated Interferon and Ribavirin for the Treatment of the Hepatitis C Virus

-- Enrollment also begins in study investigating miravirsen in combination with telaprevir and ribavirin in null responders to pegylated interferon and ribavirin --

Hørsholm, Denmark/San Diego, California, August 27, 2013 — Santaris Pharma A/S, a clinical-stage biopharmaceutical company focused on the discovery and development of RNA-targeted therapies, today announced the completion of enrollment of its Phase 2 miravirsen 12-week monotherapy study of miravirsen, a host-targeted, pan-HCV genotype antiviral agent, in subjects who were "null responders" to pegylated interferon alpha and ribavirin (peg-IFNα/RBV). The company also announced the enrollment of the first patient into another Phase 2 study of miravirsen in combination with telaprevir and ribavirin, also in null responders to peg-IFNα/RBV.

"The current standard of treatment for HCV is a combination of a direct acting-antiviral agent protease inhibitor with pegylated-interferon plus ribavirin. However, there remains a pressing need for therapeutic regimens that can attain high sustained virologic responses without peg-IFNα/RBV, which is poorly tolerated, and without drug-drug interactions. Miravirsen’s unique mode-of-action has shown potential in providing antiviral activity in patients who have failed previous treatment regimens for the hepatitis C virus," said Maribel Rodriguez-Torres, M.D., president of Fundacion de Investigacion and the study’s Principal Investigator. "We are excited to have completed enrollment and look forward to following the enrolled patients and reporting the data from this study. So far, the emerging viral load data suggest that miravirsen might be a unique treatment option, in combination with other antivirals, for the treatment of this type of difficult to treat patients."

The Phase 2, open-label study assesses the safety, antiviral activity and pharmacokinetics of miravirsen monotherapy over a total of 12 weeks of treatment. Patients enrolled in the study were chronically infected with HCV genotype 1 and had previously failed treatment with peg-IFNα/RBV therapy. Miravirsen was given as a total of five doses over five weeks, followed by a further four doses once every other week over seven weeks.

Developed using Santaris Pharma A/S proprietary Locked Nucleic Acid (LNA) Drug Platform, miravirsen is an inhibitor of miR-122, a liver specific microRNA that the hepatitis C virus requires for replication. Miravirsen is designed to recognize and sequester miR-122, making it unavailable to the hepatitis C virus. As a result, the replication of the virus is effectively inhibited and the levels of HCV RNA are profoundly reduced.

Santaris Pharma A/S has also enrolled its first patient into another Phase 2 clinical trial that will assess the safety, tolerability and antiviral activity of miravirsen given for 12 weeks in combination with telaprevir (TVR) and ribavirin (RBV) in patients with HCV infection who are non-responders to peg-IFNα/RBV.

"We are pleased to report on the progress in the miravirsen clinical program," said Michael R. Hodges, MD, Vice President and Chief Medical Officer at Santaris Pharma A/S. "We hope that data from these two 12-week studies in the hard to treat patients will confirm the earlier promising efficacy and safety data from the four-week monotherapy study in treatment naïve patients that was recently published in the New England Journal of Medicine. We continue to believe that miravirsen given in combination with direct acting-antiviral agent(s) has the potential to cure chronic HCV infection in hard-to-treat patients."


The first series of non-clinical and clinical studies demonstrated the following key attributes for miravirsen:
Miravirsen has a novel mechanism of action, inhibits a well conserved hepatic host target thus has an high barrier to resistance with predicted activity against all HCV genotypes, is not metabolized by cytochrome P450 enzymes therefore drug interactions are unlikely
In in vitro studies, miravirsen was active against all six HCV genotypes, additive activity to direct acting antiviral agents (DAAs), active against DAA resistant virus and a showed a high barrier to resistance

In clinical trials with four weeks of monotherapy, miravirsen was well tolerated, showed dose dependent antiviral activity that can be maintained weeks after the end of therapy
In two separate drug-drug interaction clinical trials, miravirsen showed no interactions with peg-IFNα/RBV or with telaprevir

About Hepatitis C

Hepatitis C infection is a viral disease caused by the hepatitis C virus that leads to inflammation of the liver. The World Health Organization estimates that approximately 3 percent of the world’s population have been infected with HCV and that some 170 million have chronic hepatitis C and are at risk of developing liver cirrhosis and/or liver canceri. Approximately 3-4 million Americans are chronically infected with an estimated 40,000 new infections per yearii. In Europe, there are about 4 million carriersi. The current standard of care treatment for genotype 1 is a protease inhibitor given with pegylated-interferon α and ribavirin. This triple combination is effective in about 70-80% of those treatedii. Even though in Europe and the United States genotype 1 is the most prevalent, there are 50-70 million people worldwide that are infected with a non-genotype 1 virus. In these patients, the combination of pegylated-interferon α and ribavirin remains the currently approved standard of care treatmentiii. Patients that are not effectively treated have an increased risk for the progression of liver disease. By 2029, total annual medical costs in the United States for people with hepatitis C are expected to more than double, from $30 billion in 2009 to approximately $85 billioniv.

About microRNAs

MicroRNAs have emerged as an important class of small RNAs encoded in the genome. They act to control the expression of sets of genes and entire pathways and are thus thought of as master regulators of gene expression. Recent studies have demonstrated that microRNAs are associated with many disease processes. Because they are single molecular entities that dictate the expression of fundamental regulatory pathways, microRNAs represent potential drug targets for controlling many biologic and disease processes.

About Locked Nucleic Acid (LNA) Drug Platform

The LNA Drug Platform and Drug Discovery Engine developed by Santaris Pharma A/S combines the company’s proprietary LNA chemistry with its highly specialized and targeted drug development capabilities to rapidly deliver LNA-based drug candidates against RNA targets, both mRNA and microRNA, for a range of diseases including cardiometabolic disorders, infectious and inflammatory diseases, cancer and rare genetic disorders. LNA is also sometimes referred to as BNA (Bicyclic or Bridged Nucleic Acid). LNA-based drugs are a promising new class of therapeutics that enable scientists to develop drugs that work through previously inaccessible clinical pathways. The LNA Drug Platform overcomes the limitations of earlier antisense and siRNA technologies to deliver potent single-stranded LNA-based drug candidates across a multitude of disease states. The unique combination of small size and very high affinity allows this new class of drugs candidates to potently and specifically inhibit RNA targets in many different tissues without the need for complex delivery vehicles. The most important features of LNA-based drugs include excellent specificity providing optimal targeting; increased affinity to targets providing improved potency; and favorable pharmacokinetic and tissue-penetrating properties that allow systemic delivery of these drugs without complex and potentially troublesome delivery vehicles.

About Santaris Pharma A/S

Santaris Pharma A/S is a privately held, clinical-stage biopharmaceutical company focused on the discovery and development of RNA-targeted therapies. The Locked Nucleic Acid (LNA) Drug Platform and Drug Discovery Engine developed by Santaris Pharma A/S combine the company’s proprietary LNA chemistry with its highly specialized and targeted drug development capabilities to rapidly deliver potent single-stranded LNA-based drug candidates across a multitude of disease states. The company’s research and development activities focus on infectious diseases and cardiometabolic disorders, while partnerships with major pharmaceutical companies address a range of therapeutic areas including cancer, cardiovascular disease, infectious and inflammatory diseases, and rare genetic disorders. The company has strategic partnerships with RaNA Therapeutics, Bristol-Myers Squibb, miRagen Therapeutics, Shire, Pfizer, GlaxoSmithKline, and Enzon Pharmaceuticals. As part of its broad patent estate, the company holds exclusive worldwide rights to manufacture and sell products that comprise LNA as active ingredient for studies performed with a view to obtaining marketing approval. Santaris Pharma A/S, founded in 2003, is headquartered in Denmark with operations in the United States. Please visit www.santaris.com for more information.


Santaris Pharma A/S® is a registered trademark of Santaris Pharma A/S. SantarisTM, Santaris PharmaTM, CureonTM and LNA-antimiR™ are trademarks of Santaris Pharma A/S.


Media Contacts: Liz Narrillos Roux, Edelman (liz.narrillosroux@edelman.com) - Office: (323)202-1074





 

Vertex’s VX-135 partial hold signals heightened FDA scrutiny toward HCV drugs

Vertex’s VX-135 partial hold signals heightened FDA scrutiny toward HCV drugs

By Christine Livoti in New York

Vertex Pharmaceuticals’ (NASDAQ:VRTX) hepatitis C virus (HCV) drug VX-135 and the recent partial clinical hold placed on it signal heightened FDA scrutiny toward HCV drugs, experts said. 

Still, most experts expressed optimism the partial hold will be removed and that the 200mg dose will advance. 

Other therapies developed to treat HCV that are similar to VX-135, a direct-acting antiviral (DAA) have been shown to trigger only transient elevations in liver enzymes, which are less of a concern.... 

Mild ALT increases seem to be quite common with many DAAs, a second European expert added. Either the elevation associated with VX-135 must be higher or the frequency greater than what has been observed with other DAAs to merit the partial clinical hold, he speculated....

Continue Reading......
 

This article is provided to FT.com readers by BioPharm Insight—a news service focused on providing insight into the most price sensitive issues in the global pharmaceutical market. www.biopharminsight.com

Hepatitis C response bill altered

Hepatitis C response bill altered

Mandatory employee drug testing eliminated

By Aaron Sanborn
asanborn@seacoastonline.com
August 27, 2013 2:00 AM

CONCORD — While two bills filed in response to the Exeter Hospital hepatitis C crisis are moving forward, one will progress with a drastically different look.

House Bill 597 would have originally required random drug testing for health care employees in the state, but it appears that the random drug testing part of the bill is now being taken out of the equation.

The bill has been in the House Health, Human Services and Elderly Affairs Committee since the spring, and in that time, the state Department of Health and Human Services and health care facilities have proposed an amendment that would only require the facilities to put in place a drug testing policy and a program for educating employees on drug addiction.

The bill's primary sponsor, state Rep. Tim Copeland, R-Stratham, said it's likely the mandatory drug testing won't happen.

"It will be weeks before anything is final, but it's not leaning in that direction," Copeland said. "It's very disappointing, but you have to work with what you have. It's give and take, sometimes you have to make concessions."

Copeland said he is now focusing his fight on putting penalties in place for health care facilities that don't have policies for drug testing or drug education.

"There has to be some sort of mechanism in place for compliance," he said.

When discussions about the bill resume next month, Copeland said he would listen to the proposals of the health care facilities.

Copeland said if he doesn't like the proposals, he has the option of reintroducing the original bill with the mandatory drug testing, but he called that an "uphill battle."

"I'm still hopeful we can all come to some type of happy medium where I can live with what they have and they can live with what I kind of wanted," he said. "I knew I wouldn't have it all when this process started; there's too many personalities and health care facilities involved."

Copeland's second bill, HB 658, which is relative to registration for medical technicians, has remained mostly intact.

The bill would establish a "Medical Technician Registration Board," that would be responsible for tracking individual health care workers in the state and maintaining a database of those workers not otherwise licensed or registered by the state.

That online database would keep the registrants' information for 15 years, along with designation of "active, inactive, suspended, revoked or retired."

The board would be responsible for accepting written complaints from the public against registrants, conducting necessary investigations and holding hearings. The board would also be required to share information with appropriate in-state and out-of-state boards.

"I'm very happy with that," Copeland said. "Something needs to be done and I'm hoping for a positive result that other states will emulate and the federal government as well, because we really need a federal database."

David Kwiatkowski, the former hospital technician who caused the hepatitis C outbreak last year at Exeter Hospital, recently pleaded guilty to federal charges and will be sentenced Dec. 3.

As a traveling technician, Kwiatkowski worked in at least 17 other hospitals in Michigan, New York, Pennsylvania, Maryland, Arizona, Kansas and Georgia from 2003 to 2011.

A total of 14 patients in Kansas and Maryland also have confirmed hepatitis C infections connected to Kwiatkowski.

Copeland said any law that can be passed to help prevent similar situations is better than doing nothing.

The bills will be discussed at the House committee's next meeting in September. The bill must be out of committee by November in order to hit the floor for the House's next session.

http://www.seacoastonline.com/articles/20130827-NEWS-308270382

Formal Hepatitis C Education-Expedites HCV Treatment and Improves Antiviral Response

Liver International

Formal Hepatitis C Education Enhances HCV Care Coordination, Expedites HCV Treatment and Improves Antiviral Response

Samali Lubega, Uchenna Agbim, Miranda Surjadi, Megan Mahoney, Mandana Khalili

Liver International. 2013;33(7):999-1007.

Discussion Only

Full Text Available Medscape

This is the first study to evaluate the impact of formal HCV patient education on receipt of HCV therapy, treatment outcomes and primary provider HCV management practices in a safety-net healthcare system. We have shown that formal HCV education expedites receipt of HCV antiviral therapy and is associated with higher rates of virologic response to HCV treatment. In addition, a majority of providers reported that the formal HCV education class improved their patient's knowledge, communication, interest in therapy, understanding of resources for HCV management and improved the overall management of the HCV-infected patients in their practice. Furthermore, a positive provider attitude towards the impact of formal HCV education was associated with higher rates of patient referral to the HCV education class.

The vulnerable patient population within the safety-net healthcare system is disproportionally affected by HCV and adverse disease outcomes[11]. A prior study in this healthcare setting has shown that formal HCV education class results in improvement of patient's HCV knowledge across all ages, racial groups, education backgrounds and socioeconomic status.^[13] Prior studies have also shown that HCV patients consider HCV education an important healthcare need that results in a marked increase in willingness to accept treatment.^{[15, 19]} In this study, the majority of primary providers also perceived that their patients' HCV knowledge had increased as a result of participation in the class. In addition, over half of providers reported that HCV education class increased their patient's interest in HCV treatment. Moreover, the HCV class appeared to improve patient's understanding of available resources for HCV care within the healthcare system, improved patient-provider communication, assisted providers in addressing patients' concerns regarding HCV disease, and improved overall HCV management within the primary care practice by provider report. These findings are important in that while primary care providers often feel confident in their ability to screen for HCV and provide initial HCV disease evaluation, and believe they should be involved in HCV co-management with specialists, they feel less confident about HCV monitoring and treatment [20–22]. Therefore, in addition to their patient's direct benefit in receipt of education, they too may benefit from additional resources and support in these areas.^{[20, 21]} Indeed, approximately 40% of providers also reported that HCV education class facilitated HCV co-management within their practices and increased access to liver specialty care services.

Interestingly, in this study primary providers did not report a significant increase in patient adherence to HCV management plans or interest in substance abuse therapy within their practices. In the practices surveyed in this study approximately 25% of providers indicated that over 25% of patients within their practice were infected with HCV. In contrast, in a national survey of primary providers, 73% of respondents had reported caring for 5 or less HCV-infected patient within the past year.^[23]

Given the high prevalence of HCV infection within practices in the San Francisco safety-net healthcare setting, it is possible that our providers had previously implemented their own mechanisms within practices to effectively address substance abuse therapy and adherence to HCV monitoring.

Whether the observed improvement in patient's knowledge and the positive impact on provider practices following formal HCV education actually influences HCV treatment initiation and treatment outcomes has not been previously studied. We have found that the time to initiation of HCV therapy was reduced by half in those patients who underwent formal HCV education compared to those who did not receive disease-specific education. This patient-centred approach to HCV education may have resulted in faster uptake of treatment by helping motivated patients to self-identify, more actively participate in their medical decision-making,^{[24, 25]} and overcome treatment-related fears that impede or delay antiviral therapy.^[26] This also suggests that the education class has resulted in efficiencies within this resource-limited healthcare system that allow better utilization of specialty care services in this population.

HCV education appears to improve adherence to HCV therapy.^{[27, 28]} However, there are only limited studies evaluating the role of patient education on HCV treatment outcome. In a study by Cacoub et al., there was a 7% increase in the rate of SVR and 6% decrease in rates of virologic relapse among those received support documents and educational material during individual sessions compared to those who did not receive disease specific education, but these findings did not reach statistical significance.^[27] Larrey et al. assessed the impact of ongoing patient education during HCV therapy.

In that study, the odds of achieving SVR were 2.5 times higher among patients who received systematic consultation by a nurse regarding patient adherence and the efficacy of therapy compared to those who did not receive the education.^[29] Similarly, we have shown that a formal HCV education class prior to HCV treatment resulted in an 18% increase in rates of SVR, and patients who received education were three times more likely to achieve SVR, independent of medication adherence and patient or viral factors. It is known that adherence to anti-HCV medications impacts rates of response to therapy. We did not observe a significant difference in patient adherence to medications in those who did and did not receive patient education. The overall rates of adherence to medication by self-report was high at 88% in this study, similar to that reported in other HCV populations ranging from 76–89%.^[30] However, our study did show that patients who attended formal HCV education were less likely to discontinue treatment because of side effects (3% vs 12%), one of the most common reasons for early discontinuation of treatment in several prior studies [9, 31, 32]. Higher rates of early discontinuation of therapy and delay in initiation of treatment in those who did not undergo HCV education, can potentially contribute to lower rates of SVR observed in this population.

The recent single topic conference cosponsored by the AASLD and CDC has emphasized the value of 'systemic changes in our healthcare delivery system and enhanced coordination of prevention and care services through education of the public and healthcare providers, and linkage of infected persons with care and treatment services to successfully prevent viral hepatitis and increase treatment efficacy'[8]. Primary care providers play a significant role in linkage of HCV-infected persons to available HCV care and treatment services. Limited data, predominantly in the HIV-HCV co-infection setting, suggest that provider attitudes affect rates of both provider HCV treatment recommendation and patient uptake of HCV treatment.^{[33, 34]} A national survey of family physicians has also shown that having a positive attitude regarding HCV care in the primary care setting was associated with more provision of HCV care services.^[21] Moreover, patients interpret a lack of referral to HCV specialty care or discussion of treatment by primary care providers as an indicator that pursuit of HCV treatment should not be considered a priority.^[35] We have shown that a positive provider attitude towards the impact of HCV education is independently associated with higher rates of referral to formal HCV education class. Therefore, increasing provider understanding of the impact of patient education on HCV care and treatment outcomes will be essential to improving patient access to HCV care services and success of antiviral therapy.

The main limitation of this study is the retrospective patient data collection, while the primary strengths include long-term patient follow-up and prospective assessment of provider attitudes and practices. Because the formal HCV education class was instituted as a mandatory component of referral of HCV patients to the liver specialty clinic, the study was limited by a lack of randomization of patients to education vs no education class when evaluating treatment outcomes. However, we were able to utilize a historical control of HCV patients prior to the initiation of education class to compare HCV treatment outcomes. Both the formal HCV education patient cohort and the historical controls likely represent individuals who are motivated to receive HCV therapy and management. Therefore, selection bias is unlikely to play a role in our finding that HCV education significantly impacts time to initiation of HCV therapy and HCV antiviral response. In addition, as the anti-viral therapy regimen (pegylated interferon in combination with ribavirin), the treating providers, and the liver specialty clinic scheduling procedures did not change before and after institution of formal HCV education, it is unlikely that differences in antiviral therapy management practices or scheduling practices overtime would impact the findings. Generalization to other non-safety-net practice settings may also be limited; nevertheless, our results present a potentially effective intervention to improve linkages to HCV specialty care, HCV treatment uptake and treatment outcome.

In summary, formal HCV education by liver specialists creates efficiencies in resource-limited healthcare systems, which not only allows better access to specialty care and treatment services but also improves HCV antiviral effectiveness. Provider attitudes towards the impact of HCV patient education play a significant role in referral to these services. Along with improvements in the healthcare delivery system, interventions directed at increasing provider knowledge of HCV disease and the important role of patient education in improving HCV management will likely enhance HCV care coordination and ultimately amplify the success of antiviral therapy, particularly in vulnerable populations.

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