Showing posts with label bms-650032. Show all posts
Showing posts with label bms-650032. Show all posts

Friday, July 13, 2012

Geno 1-4: Hepatitis C Drug Development Goes from Pony Ride to Rocket Launch

2012 pipeline report launched in Washington: HIV, HCV, TB, PEP, cure and vaccine research.

On July 21- 2012 HIV i-Base (U.K.) and Treatment Action Group (TAG) (U.S.) released their new comprehensive "2012 Pipeline Report"

The report is ready to view at the new website launched today by "TAG"

For the HCV community, there is a particular article in the report written by Tracy Swan and Karyn Kaplan you won't want to miss;

Hepatitis C Drug Development Goes from Pony Ride to Rocket Launch.
The in depth report includes some of the following topics; HCV drug resistance, DAA drug-drug interactions, nucleosides and nucleotide polymerase inhibitors, HCV protease inhibitors, the next generation of drugs, HCV quad therapy, SVR-4 ,SVR-12, interferon free therapy, ABT-450/r, ACH-1625, BI 201335, bms-650032, bms-790052, Danoprevir, genotypes 1-4, GS-7977 Formally/PSI-7977, GS-9256, Lambda, MK-7009, TMC435 and much more....

The 2012 Pipeline Report: HIV, Hepatitis C Virus (HCV), and Tuberculosis (TB) Drugs, Diagnostics, Vaccines, and Preventive Technologies in Development by Polly Clayden, Simon Collins, Colleen Daniels, Nathan Geffen, Mark Harrington, Richard Jefferys, Coco Jervis, Karyn Kaplan, Erica Lessem, and Tracy Swan is available online at:
http://www.treatmentactiongroup.org/pipeline-report/2012
and as an interactive web report at:
http://www.pipelinereport.org.

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Friday, September 30, 2011

AASLD-New Data On BMS-790052 and BMS-650032 to be presented by Bristol-Myers Squibb


September 30, 2011 11:19 AM EDT

Bristol-Myers Squibb to Present New Data Demonstrating Company’s Leadership in Liver Disease at The Liver Meeting® / AASLD Annual Meeting

  • Oral presentation on BARACLUDE® (entecavir) reinforces continued clinical development commitment in hepatitis B
  • Oral presentations on hepatitis C investigational compounds BMS-790052 and BMS-650032 demonstrate advancement of robust pipeline
  • Breadth of data highlights Company’s commitment to pursuing research that aims to improve the management of liver disease

PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol-Myers Squibb Company (NYSE: BMY) announced today that 22 abstracts on the Company’s research in liver disease have been accepted for presentation at The Liver Meeting® 2011, the 62nd annual meeting of the American Association for the Study of Liver Diseases (AASLD), in San Francisco, November 4 - 8. Bristol-Myers Squibb is advancing a portfolio of compounds that has the potential to address unmet medical needs for patients with liver disease, including BARACLUDE® (entecavir) for chronic hepatitis B (CHB), and the investigational compounds BMS-790052, BMS-650032 and PEG-Interferon lambda (Lambda) for hepatitis C (HCV) and brivanib for hepatocellular carcinoma (HCC).

Key presentations include an oral presentation on BARACLUDE monotherapy vs. combination therapy for CHB and two oral presentations of Phase II data on the Company’s investigational HCV direct-acting antivirals (DAAs). These presentations will highlight:

  • The first data from the BE-LOW study, a Phase IIIb comparative study of BARACLUDE plus tenofovir vs. BARACLUDE monotherapy in treatment-naïve adults with CHB
  • The first results from a Phase IIb study of the NS5A replication complex inhibitor BMS-790052 plus peginterferon alfa and ribavirin (alfa/RBV) in treatment-naive HCV genotype 1 and 4 patients, evaluating virologic response through 12 weeks on treatment (eRVR)
  • The first results of a Phase IIa study of the dual DAA regimen of BMS-790052 and the NS3 protease inhibitor BMS-650032 in HCV genotype 1b-infected patients who have not responded to prior alfa/RBV therapy (null responders), evaluating sustained virologic response 12 weeks post-treatment (SVR12)

“Bristol-Myers Squibb is at the forefront of innovation in researching the treatment of liver diseases. In hepatitis C, where there remain considerable unmet medical needs, our goal is to increase treatment options for patients by developing a portfolio of compounds with different mechanisms of action,” said Brian Daniels, MD, senior vice president, Global Development and Medical Affairs, Research and Development, Bristol-Myers Squibb. “The data we are presenting at the Liver Meeting help to expand our understanding of the potential efficacy and safety profiles of these investigational compounds and support the recent initiation of a broad Phase III development program in HCV.”

The Company will also present new data that further describe the mechanistic and clinical profile of Lambda, and real-world data that add to the understanding of the prevalence of and current treatment patterns in HBV, HCV and HCC, including an oral presentation of data from the BRIDGE study in HCC. The BRIDGE study is designed to develop global understanding of HCC, including assessment of treatment by geography and etiology, and associated clinical outcomes.

The complete list of Bristol-Myers Squibb data presentations is below. Abstracts can be accessed on the AASLD website at http://aasld2011.abstractcentral.com/login.

Abstract Number Title Date/Time
Hepatitis B: BARACLUDE Clinical Data
Oral

#223

Entecavir (ETV) monotherapy for 96 weeks is comparable to combination therapy with ETV plus tenofovir (TDF) in nucleos(t)ide-naïve patients with chronic hepatitis B (CHB): the BE-LOW study Presidential Plenary III

Nov. 8

8:00 am PST

Hepatitis B: Outcomes Research / Real-World Data
Poster

#458

Real World Data on Long Term Treatment Initiation in patients with Chronic Hepatitis B: cohort observations in France, Germany, Poland, Romania and Turkey Nov. 5
Poster

#478

Cost-effectiveness of entecavir versus adefovir for the treatment of chronic hepatitis B in patients with decompensated cirrhosis Nov. 5
Poster

#481

Treatment Patterns, Health Care Use, and Costs associated with First-Line Treatment for Chronic Hepatitis B with Entecavir versus Tenofovir Nov. 5
Poster

#482

Treatment Patterns, Health Care Use, and Costs associated with First-Line Treatment for Chronic Hepatitis B with Oral Antivirals Recommended by Current Guidelines versus Oral Antivirals Not Recommended by Current Guidelines Nov. 5
Hepatitis C: Direct-Acting Antiviral Data
Oral

#LB-4

Dual Oral Combination Therapy with the NS5A Inhibitor BMS-790052 and the NS3 Protease Inhibitor BMS-650032 Achieved 90% Sustained Virologic Response (SVR12) in HCV Genotype 1b-Infected Null Responders Nov. 7

3:30 pm PST

Oral

#227

BMS-790052, A NS5A Replication Complex Inhibitor, Combined with Peginterferon Alfa-2a and Ribavirin in Treatment-Naive HCV-Genotype 1 or 4 Patients: Phase 2b AI444010 Study Interim Week 12 Results Presidential Plenary III

Nov. 8

9:00 am PST

Poster #381 Evaluation of drug interaction potential of the HCV protease inhibitor BMS-650032 at 200mg twice daily (BID) in metabolic cocktail and P-glycoprotein (P-gp) probe studies in healthy volunteers Nov. 5
Poster #LB-20 Combination Therapy of Treatment-Naïve and Nonresponder Patients with HCV Genotype 1 Infection with BMS-790052, an NS5A Replication Complex Inhibitor, in Combination with Peginterferon Alfa-2a and Ribavirin Nov. 7
Poster #LB-22 BMS-790052, an NS5A Replication Complex Inhibitor, in Combination with Peginterferon Alpha-2b and Ribavirin in Japanese Treatment-Naïve and Nonresponder Patients with Chronic HCV Genotype 1 Infection Nov. 7
Poster #1362 Single-Dose Pharmacokinetics of BMS-790052 in Subjects with Hepatic Impairment Compared With Healthy Subjects Nov. 7
Poster #1340 BMS-790052 Has No Effect on the Pharmacokinetics of a Combined Oral Contraceptive Containing Ethinyl Estradiol and Norgestimate in Healthy Female Subjects Nov. 7
Hepatitis C: PEG-Interferon Lambda Data
Poster #376 The Effect of Pegylated Interferon Lambda on the Expression of Interferon Stimulated Genes in Whole Blood in Chronic Hepatitis C Patients in a Phase 2a Study Nov. 5
Poster #1058 Implementation of an HCV Model for Il-28B Genotype Treatment Duration Optimization and Cure Rate Maximization for Pegylated Interferon Lambda Nov. 6
Poster #1343 Pegylated Interferon Lambda Ameliorates Ribavirin (RBV)-Induced Anemia in HCV Patients by Maintaining Compensatory Erythropoiesis: Analysis of EMERGE Phase 2b Results through Week 12 Nov. 7
Poster #1344 Safety and Efficacy of Pegylated Interferon Lambda (peg-lambda) Compared to Pegylated Interferon α-2a (peg-alfa) in HCV-Infected Patients (G1/2/3) With Compensated Cirrhosis: EMERGE Phase IIB Efficacy and Safety Results through Week 12 Nov. 7
Poster #1363 Less severe flu-like symptoms with PEG-Interferon Lambda in Phase IIb Study of treatment-naive chronic hepatitis C (CHC) patients Nov. 7
Hepatitis C: Epidemiology / Real-World Data
Poster #412 Prevalence of HCV and Host IL28B Genotypes in China Nov. 5
Poster #1045 Adverse Events in Patients With Chronic Hepatitis C Treated With PegIFN-alfa and Ribavirin in Real-World Setting Nov. 6
Poster #1084 Virologic Response among Hepatitis C (HCV) Patients Treated in Clinical Practice Nov. 6
Poster #1736 Single nucleotide polymorphisms near IL28B and IL28A genes are associated with spontaneous seroclearance of HCV RNA in untreated patients with HCV infection Nov. 7
Hepatocellular Carcinoma: Outcomes Research
Oral

#267

Observations of Hepatocellular Carcinoma (HCC) Management Patterns from the Multinational HCC BRIDGE Study: First Overall Analysis of the North American Cohort Nov. 811:15 am PST

INDICATION and IMPORTANT SAFETY INFORMATION about BARACLUDE® (entecavir)

INDICATION

BARACLUDE is indicated for the treatment of chronic hepatitis B virus (HBV) infection in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease.

The following points should be considered when initiating BARACLUDE:

  • This indication is based on histologic, virologic, biochemical, and serologic responses in nucleoside-treatment-naïve and lamivudine-resistant adult subjects with HBeAg-positive or HBeAg-negative chronic HBV infection and compensated liver disease.
  • Virologic, biochemical, serologic, and safety data are available from a controlled study in adult subjects with chronic HBV infection and decompensated liver disease.
  • Virologic, biochemical, serologic, and safety data are available for a limited number of adult subjects with HIV/HBV co-infection who have received prior lamivudine therapy.

IMPORTANT SAFETY INFORMATION

WARNINGS: SEVERE ACUTE EXACERBATIONS OF HEPATITIS B, PATIENTS CO-INFECTED WITH HIV AND HBV, and LACTIC ACIDOSIS AND HEPATOMEGALY

  • Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued anti-hepatitis B therapy, including entecavir. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue anti-hepatitis B therapy. If appropriate, initiation of anti-hepatitis B therapy may be warranted.
  • Limited clinical experience suggests there is a potential for the development of resistance to HIV (human immunodeficiency virus) nucleoside reverse transcriptase inhibitors if BARACLUDE is used to treat chronic HBV infection in patients with HIV infection that is not being treated. Therapy with BARACLUDE is not recommended for HIV/HBV co-infected patients who are not also receiving highly active antiretroviral therapy (HAART).
  • Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues, alone or in combination with antiretrovirals.

Warnings and Precautions

  • Before initiating BARACLUDE therapy, HIV antibody testing should be offered to all patients. BARACLUDE has not been studied as a treatment for HIV infection and is not recommended for this use.
  • Lactic acidosis with BARACLUDE use has been reported, often in association with hepatic decompensation, other serious medical conditions, or drug exposures. Patients with decompensated liver disease may be at higher risk for lactic acidosis. BARACLUDE should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity.

Adverse Reactions

  • In clinical trials in patients with compensated liver disease, the most common (≥3%) adverse reactions of any severity with at least a possible relation to study drug for BARACLUDE-treated subjects were headache, fatigue, dizziness, and nausea. In these trials, the most common adverse reactions of moderate to severe intensity (grades 2-4) were diarrhea, dyspepsia, nausea, vomiting, fatigue, headache, dizziness, somnolence, and insomnia.
  • In the decompensated liver disease trial, the most common adverse reactions of any severity among patients treated with BARACLUDE, regardless of causality, included: peripheral edema (16%), ascites (15%), pyrexia (14%), hepatic encephalopathy (10%), and upper respiratory infection (10%). In this trial, 18% (18/102) of BARACLUDE patients and 20% (18/89) of adefovir patients died during the first 48 weeks of therapy. The majority of those deaths were due to liver related causes.

Drug Interactions

BARACLUDE is primarily eliminated by the kidneys, therefore coadministration of BARACLUDE with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of either entecavir or the coadministered drug. Patients should be monitored closely when receiving BARACLUDE with other renally-eliminated drugs.

Pregnancy and Nursing Mothers

  • There are no adequate and well-controlled studies of BARACLUDE in pregnant women. BARACLUDE should be used during pregnancy only if clearly needed and after careful consideration of the risks and benefits.
  • There are no studies on the effect of BARACLUDE on transmission of HBV from mother to infant. Therefore, appropriate interventions should be used to prevent neonatal acquisition of HBV.
  • It is not known whether BARACLUDE is excreted into human milk; however, many drugs are excreted into breast milk. Due to the potential for serious adverse reactions in nursing infants from BARACLUDE, risks and benefits should be considered when deciding whether to discontinue breast-feeding or discontinue BARACLUDE in nursing women.

Pediatric Use

  • Safety and effectiveness of BARACLUDE in pediatric patients below the age of 16 years have not been established.

Renal Impairment

  • Dosage adjustment of BARACLUDE is recommended for patients with a creatinine clearance <50 mL/min, including those on hemodialysis or continuous ambulatory peritoneal dialysis.
  • The safety and efficacy of BARACLUDE in liver transplant recipients are unknown. Renal function must be carefully monitored both before and during treatment with BARACLUDE in a liver transplant recipient who has received or is receiving an immunosuppressant that may affect renal function, such as cyclosporine or tacrolimus.

Dosage and Administration

BARACLUDE should be administered on an empty stomach (at least 2 hours after a meal and at least 2 hours before the next meal).

The recommended dose of BARACLUDE:

  • in nucleoside-naïve adults and adolescents (16+ yrs) with compensated liver disease is 0.5 mg once daily
  • in adults and adolescents (16+ yrs) with compensated liver disease, and refractory to lamivudine or with known lamivudine or telbivudine resistance mutations (rtM204I/V with or without rtL180M, rtL80I/V, or rtV173L) is 1 mg once daily
  • in adults with decompensated liver disease is 1 mg once daily

The optimal duration of treatment with BARACLUDE for patients with chronic HBV infection and the relationship between treatment and long-term outcomes such as cirrhosis and hepatocellular carcinoma are unknown.

Additional Information

Patients should be advised that treatment with BARACLUDE has not been shown to reduce the risk of transmission of HBV to others through sexual contact or blood contamination.

Please see Full Prescribing Information, including boxed WARNINGS, available at www.BARACLUDE.com.

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information, please visit http://www.bms.com or follow us on Twitter at http://twitter.com/bmsnews.

Bristol-Myers Squibb CompanyMedia:Cristi Barnett, 609-252-6028cristi.barnett@bms.comorInvestors:John Elicker, 609-252-4611john.elicker@bms.com

Source: Bristol-Myers Squibb Company

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Friday, February 25, 2011

Hepatitis C News; Antiviral Therapy for HCV "Attitudes Regarding Future Use" Also "BMS-790052, BMS-650032"


Coverage From NATAP
Reported by Jules Levin
The 21st Conference of the Asian Pacific Association for the Study of the LiverAPASL
Feb 17-20, 2011
Bangkok, Thailand


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"In summary, the responses to this Internet-based survey of more than 1,000 current HCV treaters indicated that although the majority of respondents appear ready to utilize DAA agents in the future, referrals to "hepatitis C experts" will increase when these agents become available. In addition, future referrals to ID specialists appear to be limited. Finally, as more than half of respondents to the survey with "minimal knowledge" of DAA therapies also appear to be willing to utilize these compounds in the future, significant provider education will be required to minimize inappropriate use of these agents."


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Just In;

Scripps Pioneers Individualized Medicine by Offering Genetic Testing to Hepatitis C Patients
Individualized Therapies Now Available for Drug Treatment of Hepatitis C
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SAN DIEGO, Feb. 25, 2011 (GLOBE NEWSWIRE) -- Scripps Health is one of the first health systems in the United States to offer genetic testing as part of its care for hepatitis C patients planning to undergo drug treatment.
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The tests offer hope to the more than 4 million patients diagnosed annually in the U.S. with hepatitis C and could spare them from taking interferon, which is commonly prescribed. Interferon causes flu-like symptoms as a side effect and costs more than $50,000 annually. Instead, the genetic test determines whether patients have a common gene variant that predicts a favorable cure rate if they are treated with the drug combination therapy of pegylated interferon and ribavirin.
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A manuscript describing this approach to treatment, authored by Paul J. Pockros, MD, clinical director of research at the Scripps Translational Science Institute, head of the Division of Gastroenterology and Hepatology and director of the Liver Disease Center at Scripps Clinic, will be published in the journal Drugs in March.
"This is a huge step forward in the movement toward individualized medicine," said Dr. Pockros, "As a physician, knowing what drug therapies will have benefit and which ones won't based on a patient's IL28B genotype is significant because we are able to be more targeted in our approach to treatment."
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This is the first of numerous genetic tests that will accurately give doctors vastly improved data, leading to better prescription of drug treatments. Later this year, a second test will be available that will accurately predict anemia in hepatitis C patients taking the pegylated interferon and ribavirin drug combination. Anemia is one of the most common side effects of the regimen. This will allow doctors to modify the therapy before starting the regimen to prevent patients from developing this problematic side effect.
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Genetic testing for hepatitis C patients carries significant implications for patient care, as there are more than 4 million infected people in the United States, most of them undiagnosed and untreated.
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Scripps Clinic now routinely orders IL28B genotyping on all patients with Hepatitis C who are potential candidates for anti-viral therapy. If the patients have a favorable IL28B genotype and advanced fibrosis on liver biopsy, doctors can initiate therapy with the current standard of care. If patients have a less favorable genotype or they have mild fibrosis, doctors can recommend waiting for FDA approval of direct acting antiviral drugs to improve their chances of response.
Currently, LabCorps Diagnostics is performing the IL28B testing for Scripps patients, a procedure covered by most insurance plans. The results are transmitted to the treating physician in about one week and the treatment choice is tailored based on the patient's likelihood to have a favorable response.
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The hepatitis C genetic testing is the latest example of Scripps' leadership in individualized medicine. Scripps doctors were the first to use genetic testing for cardiovascular patients planning to undergo elective stent procedures to determine if they have one or more of the common gene variants linked to an inability to metabolize the anti-clotting drug Plavix (clopidrogel). Plavix is the second-most commonly prescribed drug in the United States and is given to most patients after they receive coronary stents.
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ABOUT SCRIPPS HEALTH
Founded in 1924 by philanthropist Ellen Browning Scripps, Scripps Health is a $2.3 billion nonprofit community health system based in San Diego, Calif. Scripps treats a half-million patients annually through the dedication of 2,500 affiliated physicians and 13,000 employees among its five acute-care hospital campuses, home health care services, and an ambulatory care network of physician offices and 22 outpatient centers and clinics. Scripps has been recognized by Thomson Reuters as one of the Top 10 health systems in the nation for quality care. Scripps is also at the forefront of clinical research, genomic medicine, wireless health and graduate medical education. With three highly respected graduate medical education programs, Scripps is a longstanding member of the Association of American Medical Colleges. More information can be found at www.scripps.org.
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This information was brought to you by Cision http://www.cisionwire.com
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Prediction of response to Hep C therapy using genetic polymorphisms
The decision model was generated by data mining analysis.
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The model predicted sustained virological response with 78% specificity Journal of Hepatology

March's issue of the Journal of Hepatology investigates the pre-treatment prediction of response to pegylated-interferon plus ribavirin for chronic hepatitis C using genetic polymorphism in IL28B and viral factors.

Pegylated interferon and ribavirin therapy for chronic hepatitis C virus genotype 1 infection is effective in 50% of patients.

Recent studies revealed an association between the IL28B genotype and treatment response.
Dr Masayuki Kurosaki and colleagues from Japan developed a model for the pre-treatment prediction of response using host and viral factors.

Data were collected from 496 patients with hepatitis C genotype 1 treated with Pegylated interferon/ribavirin at 5 hospitals and universities in Japan.

IL28B genotype and mutations in the core and intereron sensitivity determining region (ISDR) of hepatitis C were analyzed to predict response to therapy.

The IL28B polymorphism correlated with early virological response and predicted null virological response and sustained virological response independent of other covariates.
The research team found that mutations in the ISDR predicted relapse and sustained virological response independent of IL28B.

The decision model revealed that patients with the minor IL28B allele and low platelet counts had the highest null virological response and lowest sustained virological response.
The researchers found that those with the major IL28B allele and mutations in the ISDR or high platelet counts had the lowest null virological response and highest sustained virologicial response.

The team found that the model had high reproducibility and predicted sustained virological response with 78% specificity and 70% sensitivity.
Dr Kurosaki's team concludes, "The IL28B polymorphism and mutations in the ISDR of hepatitis C were significant pre-treatment predictors of response to pegylated-interferon/ribavirin."
"The decision model, including these host and viral factors may support selection of optimum treatment strategy for individual patients."

In The News

Twelve Pregnant Women Die In Indian Hospital, Contaminated IV Fluids Suspected
Updated: Friday, 25 Feb 2011, 8:29 AM EST Published :

By: AFP
Twelve pregnant women died in 10 days in an Indian government hospital, with contaminated fluids administered during childbirth suspected to be the cause, reports said Friday.
Another five women were in serious condition, according to doctors at Umaid Hospital in the city of Jodhpur, in a case that highlights the often-poor standards of care in state-run health facilities in India.

The first death occurred Feb. 13, and a meeting of leading doctors that was held three days later failed to identify the cause, The Indian Express newspaper reported, citing doctors and officials at the hospital.

"All the women died after severe hemorrhaging, and for now, we believe the cause might be an infection after they were administered tainted IV fluids," Umaid Hospital superintendent N.G. Chaggani told the newspaper.

Police lodged a case against the local company that supplied the fluids and the Indian manufacturer.

"We have begun our investigation and are checking the suspected stock," Jodhpur police commissioner Bhupendra Kumar Dak told the Times of India newspaper.
India has a two-speed medical system in which shabby and often insanitary state facilities coexist with state-of-the-art private hospitals that cater for wealthy overseas medical tourists who visit India for low-cost surgery.
In July, Indian news channel NDTV reported that at least eight children were infected with HIV by blood transfusions given at Umaid Hospital in the previous six months, while 43 contracted Hepatitis C.

In addition to poor standards of care, most Indians are required to pay for their health care out of their own pockets, with the state and insurance companies picking up just a fraction of overall spending.

A major study published in January in British medical journal The Lancet said payments by individuals accounted for 71.1 percent of spending on health, with 39 million Indians pushed back below the poverty line each year because of the cost of care.
Copyright 2011 AFP. All rights reserved.
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Cancer


Monitoring circulating tumor cells using gold nanoparticles
Once these tumor cells are tagged with the gold nanoparticles, laser illumination reveals which cells are tumors in the bloodstream. This technique was tested on 19 patients with head and neck cancer, and showed excellent correlation with previous techniques. If this method can be validated in larger studies, it shows promise as a faster, more economical method to detect circulating tumor cells.
“The key technological advance here is our finding that polymer-coated gold nanoparticles that are conjugated with low molecular weight peptides such as EGF are much less sticky than particles conjugated to whole antibodies,” says Shuming Nie, PhD, a professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. “This effect has led to a major improvement in discriminating tumor cells from non-tumor cells in the blood.”.. read more...

Hershey, PA Posted on February 24th, 2011

Nanotechnology may open a new door on the treatment of liver cancer, according to a team of Penn State College of Medicine researchers. ...

Researchers evaluated the use of molecular-sized bubbles filled with C6-ceramide, called cerasomes, as an anti-cancer agent. Ceramide is a lipid molecule naturally present in the cell's plasma membrane and controls cell functions, including cell aging, or senescence.Hepatocellular carcinoma is the fifth most common cancer in the world and is highly aggressive. The chance of surviving five years is less than five percent, and treatment is typically chemotherapy and surgical management including transplantation."The beauty of ceramide is that it is non-toxic to normal cells, putting them to sleep, while selectively killing cancer cells," said Mark Kester, Ph.D., G. Thomas Passananti Professor of Pharmacology.Cerasomes, developed at Penn State College of Medicine, can target cancer cells very specifically and accurately, rather than affecting a larger area that includes healthy cells. The problem with ceramide is that as a lipid, it cannot be delivered effectively as a drug. To solve this limitation, the researchers use nanotechnology, creating the tiny cerasome, to turn the insoluble lipid into a soluble treatment.
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Healthy You
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This year will see an unprecedented surge in the number of Americans becoming eligible for Medicare, as the leading edge of the Baby Boom generation begins to turn 65. This will spark a fundamental shift in the US...

High HDL Levels Tied to Longevity in Men
Friday, February 25, 2011 7:17 AM
Men who reach their 85th birthdays tended to have high levels of good cholesterol while in their 60s, a new study says.

Researchers found that men with the highest good (HDL) cholesterol were 28 percent less likely to die before they reached 85, compared to men in the lowest HDL group.
This paper, published in the American Journal of Cardiology, adds to the evidence that HDL is important for a long life, said Dr. Nir Barzilai, who heads the Institute for Aging Research at Albert Einstein College of Medicine in New York and was not part of the study.
However, "we always have to remember that it's an association," and it does not mean that having high HDL increases life span, he told Reuters Health.

About 12 million men suffered from heart disease and stroke in 2006, but high levels of HDL cholesterol may reduce the risks, according to the American Heart Association.
Low levels of HDL, less than 40 milligrams per deciliter (mg/dL) of blood for men, are known to increase the risk of heart disease, according to the heart association.

The researchers, from the Massachusetts Veterans Epidemiology and Research Information Center in Boston, looked at the medical records of about 650 veterans when they were around 65 years old, then grouped them based on HDL levels.

Starting with low levels of 40 mg/dL, they found that for each 10 mg/dL increase of HDL, the men were 14 percent less likely to have died by 85. Overall, 375 survived to that age.
Also, fewer of the men with higher HDL were overweight, and they tended not to have more than two drinks a day. And fewer of them had heart disease or smoked, compared to the lowest HDL group.

These other factors might have had an effect on survival, Barzilai said. However, the researchers did account for this, and still showed a link between reaching 85 and high HDL levels, he told Reuters Health.

"It's difficult to change HDL levels," Barzilai said. Exercise might raise it a few points, but it isn't a very efficient way to improve, he said. "We need to get a drug eventually."
Merck and Roche are both working on an HDL-raising drug, he told Reuters Health. Pfizer stopped its research into another such drug, torcetrapib, in 2006 because people taking it along with Lipitor in a study had a higher rate of death.

The B-vitamin niacin may raise HDL levels 15 to 35 percent. However, side effects can include liver damage and increased blood sugar, according to the Mayo Clinic.
A three-month supply costs about $9. Niacin is also found in dairy products, lean meats, nuts, eggs, and fish.
However, it's unclear how much raising HDL will prevent heart disease, Barzilai said, so whether drugs might improve people's health remains to be seen.
The study authors could not be reached by deadline.
© 2011 Reuters. All rights reserved. Republication or redistribution of Reuters content, including by caching, framing or similar means, is expressly prohibited without the prior written consent of Reuters.



A 48-year-old man was sentenced yesterday to six months' imprisonment suspended for two years and 200 hours of unpaid work for selling and supplying herbal medicines to the public without a marketing authorisation...

Dan Frosch(The New York Times, February 21, 2011)"
Just 15 states and the District of Columbia license naturopaths, according to the American Association of Naturopathic Physicians. That process requires completion of a four-year accredited, specialized school, passing an exam and a certain amount of clinical training. This year, at least 11 states are trying to pass licensing legislation…Naturopaths who favor licensing say they are not interested in becoming medical doctors...Moreover, they contend that it is dangerously easy to get a certificate that shows expertise in naturopathy and people need some way of discerning between a knowledgeable naturopath and a quack."
As thousands of breast cancer survivors battle persistent fatigue, a Michigan State University nursing researcher is studying whether acupressure - a technique where physical pressure is applied to acupuncture points by the...

Off The Cuff
Shan Juan and Cang Wei (China Daily, February 21, 2011)"

About 70 percent of Chinese families improperly use medicine, according to a survey conducted by China Nonprescription Medicines Association. The survey, which polled 10,000 people…concluded that a majority of the populace tends to go to drugstores to buy medications for minor sicknesses instead of seeing a doctor…The reasons for concern are particularly pressing on the mainland, where, because of loose supervision, the public can often buy prescription drugs at drugstores without doctors' prescriptions."

Bruce Japsen(Chicago Tribune, February 19, 2011)
Hospitals across the country are running out of key drugs used in surgeries and to treat some diseases…causing doctors to turn to older treatments...Part of the shortage is being caused by manufacturing issues and quality-control problems at a number of companies…Drugmakers say they are obliging tougher safety rules put in place by the U.S. Food and Drug Administration, which has intensified scrutiny to avoid allowing unsafe medicines on the market."

Scott Hiaasen and David Ovalle (The Miami Herald, February 23, 2011)
Narcotics agents across South Florida descended on more than a dozen pain clinics...in the most dramatic effort yet to curb the region’s booming business of illegal prescription narcotics…These clinics have exploded all over South Florida in recent years…making the region the prime supplier of illegal pills in the eastern United States. The clinics attract drug couriers posing as patients who travel from Kentucky, Ohio and West Virginia, where an oxycodone pill can sell for 10 times the price charged by a South Florida doctor.

An undiagnosed genetic disease appears to have been the critical factor in the 2009 death of a University of Chicago researcher from plague, investigators have concluded.
The 60-year-old man, Malcolm Casadaban, PhD, had been working with an attenuated strain of Yersinia pestis, the plague bacterium, as part of his research. The strain was subsequently cultured from his blood after death.

Although a forensic team from state and local health departments and the CDC were unable to determine how exactly Casadaban came into contact with the organism, autopsy results also indicated he had hereditary hemochromatosis, according to a report in the Feb. 25 issue of the CDC's Morbidity and Mortality Weekly Report.

Big Pharma

Drug R&D Costs Are Less Than Estimated -- So Why the High Prices?
André Picard(The Globe and Mail, Toronto, February 23, 2011)
"It costs, on average, $1.3-billion (U.S.) in research and development to bring a new drug to market. That level of investment in R&D by Big Pharma justifies the high cost of prescription drugs. Those statements are repeated so often that they have come to be accepted as fact. But are they fact or fiction? An article in the current edition of the journal BioSocieties...argues that the real cost of R&D is...a fraction of the commonly cited estimate…If R&D costs are only a fraction of what is asserted, then what is the justification for high prescription drug prices?"

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Monday, November 8, 2010

AASLD 2010 Summary Of Hepatitis C Oral Inhibitors

This entry of new investigational oral inhibitors is only a brief collection of data accumulated from following sites: HCV Advocate ,CCO, Medpage, AASLD, NATAP HIV and Hepatitis,Medscape, The Street.com. Biopharma report and TheMedGuru
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The links through out this summary provide the additional information needed to give a complete and accurate profile of these new agents.
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The AASLD has released "The Best of The Liver Meeting® State-of-the-Art-Lectures" . The presentation's are available in a multimedia format. As the remainder of these lectures are released they will be added to the blog.
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*A link to "The Best of the liver meeting" is on the sidebar
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This summary will be updated over the next few weeks with a link also on the sidebar with the current review date.
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*data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
Telaprevir
Telaprevir is an investigational oral protease inhibitor used in combination with pegylated interferon plus ribavirin and is being developed by Vertex in collaboration with Johnson & Johnson.
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The two trials named "ADVANCE and ILLUMINATE" were for patients with genotype 1 who have not previously treated.

Response-guided therapy (Response guided therapy is intended to enable the physician to determine the duration of combination therapy based on a patient's viral response during treatment) was used in ADVANCE, whereby patients whose virus was undetectable at weeks 4 and 12 of treatment with telaprevir-based therapy were eligible to reduce their treatment from 48 weeks to 24 weeks.

The Phase 3 ILLUMINATE trial was designed to confirm both the use of *response-guided therapy and to evaluate whether there was any benefit to extending total treatment duration from 24 to 48 weeks."

In ADVANCE and ILLUMINATE, 58% and 65% of people, respectively, met these criteria for 24-week total treatment. In ILLUMINATE there was no benefit in extending therapy to 48 weeks.

Phase 3 REALIZE
Trial REALIZE was the second pivotal Phase 3 trial and was designed to evaluate telaprevir-based regimens in people who had received pegylated-interferon-based therapy but did not achieve a cure. REALIZE is the only Phase 3 clinical trial to date of an investigational direct-acting antiviral to include all major subgroups of difficult-to-treat patients including null responders, who were defined as people who had a less than a 2 log10 reduction in viral load by week 12 of a prior course of therapy.

The Results
.ADVANCE
Overall in ADVANCE, 75% of people treated with a telaprevir-based combination regimen for 12 weeks, followed by an additional 12 or 36 weeks of pegylated-interferon and ribavirin alone, achieved SVR, compared to 44% of people treated with 48 weeks of pegylated-interferon and ribavirin alone.

ILLUMINATE
In ILLUMINATE, 72% of people overall achieved SVR with telaprevir-based therapy. New data from this study showed that 60% of African Americans/Blacks and 63% of people with advanced liver fibrosis or cirrhosis achieved SVR with telaprevir-based therapy in the overall study analysis. Of African Americans/Blacks whose virus was undetectable at weeks 4 and 12, 88% of people achieved SVR in both the 24-week and 48-week randomized treatment arms. There was no control arm of pegylated-interferon and ribavirin alone in ILLUMINATE.

REALIZE
Results of the REALIZE trial showed that 65 percent of patients treated with telaprevir plus the standard of care were cured, or sustained viral response compared to 17 percent of patients in the control group who were re-treated with just the standard of care.

SVR In The Three Different Groups Were As Follows:
86 percent of re-lapsers were cured after telaprevir treatment compared to 24 percent in the control arm.
Among the second group, the cure rate for the telaprevir-treated patients was 57 percent compared to 15 percent for the control arm.

Control Arm = *SOC pegylated interferon plus ribavirin

Finally, in the last group which consisted of the most difficult to treat patients, telaprevir achieved a 31 percent cure rate compared to 5 percent for the control arm. Results across all three patients types were statistically significant in favor of telaprevir over standard of care, officials report.

Complete Information

Side Effects :In ADVANCE, discontinuation of telaprevir or placebo only due to adverse events during the telaprevir treatment phase occurred in 11% of people in the 12-week telaprevir arm, 7% of people in the 8-week telaprevir arm and 1% of people in the control arm. In ILLUMINATE, 12% of people overall discontinued telaprevir only due to adverse events during the telaprevir treatment phase.

Discontinuation of all drugs due to either rash or anemia was low in both studies (1% to 3%). Rash was primarily characterized as eczema-like, manageable and resolved upon stopping telaprevir. Ninety-two percent and 95% of rash was mild to moderate in ADVANCE and ILLUMINATE, respectively. Rash was managed with the use of topical corticosteroids and antihistamines, and anemia was primarily managed by reducing the dose of ribavirin. The use of erythropoiesis-stimulating agents (ESAs) were not allowed in any of the Phase 3 clinical studies.

Discontinuation (%) of all drugs during the telaprevir treatment phase

ADVANCE

12-week telaprevir arm ..................................7%
8-week telaprevir arm......................................8%
Control Arm.................................... 4%

ILLUMINATE*
Total .................................................7%*

There was no control arm in ILLUMINATE

Telaprevir may have * fewer side effects (like anemia) than boceprevir.

Vertex announced a new trial which will be called the "OPTIMIZE" and is for genotype 1 patients who have not previously treated.

AASLD/2010 Telaprevir 3 Studies Showed Superior SVR (Viral Cure)Regardless of Race/Stage Of Liver Disease

AASLD:Telaprevir SVR/Decreased Adverse Events Presented Nov 2

Telaprevir will be filing their FDA Application in the next few weeks
Telaprevir® Vertex To File FDA Application “Within Weeks”
The Cost : Telaprevir


Boceprevir
Boceprevir is also an investigational oral HCV protease inhibitor used in combination with pegylated interferon plus ribavirin and is being developed by Merck.

*Excerpt:
The two trials were the SPRINT-2 trial which enrolled genotype 1 patients who have never treated previously. The RESPOND-2 trial enrolled genotype 1 patients who previously treated but did not respond to or relapsed after treatment.

Merck released final results from two phase-3 studies of boceprevir, saying it produced “significantly higher” results compared with patients in the control group.

In the "RESPOND 2" trial at 24 weeks after conclusion of treatment, the patients treating in the *control arm with "no telaprevir" or with only *SOC achieved a SVR of 21 percent.

Adding Boceprevir to the treatment increased SVR to 59 percent for the second arm *(Second arm received 4 weeks of lead-in therapy of peginterferon alpha 2b and ribavirin followed by response-guided therapy of peginterferon alpha 2b and ribavirin combined with 800 mg of Boceprevir three times a day) and 67 percent for the third arm *(Third arm received 4 weeks of lead-in therapy of peginterferon alpha 2b and ribavirin followed by 44 weeks of peginterferon alpha 2b and ribavirin combined with 800 mg of Boceprevir).

It was noted that previous relapsers fared better than nonresponders in all arms. The therapy was well-tolerated, and the most common reason for discontinuing treatment was for patients who still had detectable HCV-RNA at week 12.

From HCV Advocate

SPRINT-2
The SPRINT-2 study included 1,097 HCV genotype 1
treatment-naïve patients (never been treated). The treatment
protocol consisted of a 4 week lead-in phase of
PegIntron plus ribavirin (without boceprevir), followed
by the triple combination of boceprevir, PegIntron
and ribavirin. Duration and continuation of treatment
was guided by the type of on-treatment response to the
medications.*
.The SVR or sustained virological response rates (HCVRNA negative 24 weeks after the last dose of medicine is taken) by different treatment arms are listed below:
.a. If HCV RNA (viral load) negative at week 8 through week 24,
triple therapy was continued for a total treatment duration of 28 weeks;
sustained virological response (SVR) = 63%
a. If HCV RNA positive at week 8 but undetectable at week 24, boceprevir was stopped at week 28 and PegIntron/ribavirin combination therapy (without boceprevir) was continued for a total treatment duration of 48 weeks;SVR = 66%
a. The control arm was standard of care – PegIntron plus ribavirin—with a treatment duration of 48weeks;SVR = 38%
.African Americans/Blacks—Treatment Response
There were also 159 African American/Black patients in the study—
African Americans/Blacks comprised 15% of the patient population in this trial.
The SVR rates by different treatment arms are listed below:
.a. If HCV RNA negative at week 8 through week 24,triple therapy was continued for a total treatment duration of 28 weeks: SVR = 42%
a.If HCV RNA positive at week 8 but undetectable at week 24, boceprevir was stopped at week 28 andPegIntron/ribavirin combo therapy without boceprevir) was continued for a total treatment duration of 48weeks; SVR = 53%
a. The control arm was standard of care – PegIntron plus ribavirin—with a treatment duration of 48weeks; SVR = 23%
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*If any patients were HCV RNA positive at week 24 all treatment was stopped.


HCV RESPOND 2
The RESPOND 2 study included 403 HCV genotype 1
“treatment-failure” patients. The study included a 4
week lead-in phase of PegIntron plus ribavirin
(without boceprevir), followed by the triple combination
of boceprevir, PegIntron and ribavirin1 and treatment
duration was based on type of on-treatment response.
.The SVR rates and duration of treatment periods for all
patients are listed below.
a. If HCV RNA negative at week 8 and at week 12 the total
treatment duration was 36 weeks; SVR = 59%
a. IF HCV RNA positive at week 8, but undetectable at
week 12, boceprevir was stopped at week 36 and the
combination of PegIntron/ribavirin was continued for a
total treatment duration of 48 weeks; SVR = 66%
a. Control arm was standard of care – combination of
PegIntron plus ribavirin—for a total treatment duration
of 48 weeks; SVR = 21%
*If any patients were HCV RNA positive at week 12 all
treatment was stopped.
.It is important to know that the treatment duration in the
boceprevir containing arms were 28, 36 or 48 weeks
depending on the type of on-treatment response.

Side Effects: Treatment appeared to be associated with two side effects compared with placebo -- anemia and a distorted sense of taste, or disgeusia. Overall, patients on treatment had greater use of erythropoietin "Note (rescue drugs)" to treat anemia compared with controls (43% for short- and full-course, versus 24% of those on placebo). More boceprevir patients also had to reduce their treatment dose due to anemia (20% and 21% versus 13%). Other adverse events included nausea, headache, and fatigue, at similar rates across all three groups".

Merck began submission of a new drug application for boceprevir on a rolling basis and expects to complete that process by the end of the year.

AASLD Presented Nov 2/Final Results of Clinical Trial on Boceprevir
AASLD:Hepatitis C Drug Boceprevir Six Months of Novel Agent Works
Boceprevir Achieved Significantly Higher SVR Rates In Treatment-Failure And Treatment-Naïve Adult Patients With Chronic Hepatitis C Genotype 1 Compare

Telaprevir Over Boceprevir?
AASLD:Telaprevir/Boceprevir/Similar Cure Rates/Shorter Treatment Duration


TMC435
.TMC435 is a protease inhibitor used in combination with peg-interferon and ribavirin and is being developed by Medivir and Tibotec Pharmaceuticals .

Tibotec is a global pharmaceutical and research development company. The Company's main research and development facilities are in Beerse, Belgium with offices in Titusville, NJ and Cork, Ireland.
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*Excerpt :
In the PILLAR study genotype 1 treatment-naive patients were enrolled in a week-24 planned interim analysis of response-guided treatment.

The compound is given once a day -- an easier regimen than that of the two protease inhibitors closest to market, boceprevir and telaprevir, which are administered thrice daily.
As well, the new data reported for the Tibotec protease TMC435 shows potency with 95% achieving week 24 response rate.

The results showed that in the four TMC435 treatment groups between 79 and 86 percent of patients were able to stop all therapy at Week-24, according to the response criteria defined in the study protocol. There were no relevant differences for adverse events between TMC435 treatment groups and placebo

The PILLAR study [Protease Inhibitor TMC435 trial assessing the optimaL dose and duration as once daiLy Anti-viral Regimen] (TMC435-C205; NCT00882908) is an ongoing, five-arm, global phase 2b randomized, double-blind, placebo controlled study in 386 treatment-naive patients. TMC435 was administered in doses of 75mg or 150mg q.d. for either 12 weeks or 24 weeks in combination with 24 weeks of peg-interferon and ribavirin (PR).

Patients in the placebo arm receive 24 weeks of placebo plus peg-interferon and ribavirin followed by 24 additional weeks of peg-interferon and ribavirin treatment. The primary endpoint of the study is sustained virologic response at Week-72 (SVR24). The PILLAR study is being conducted in 13 countries in Europe, North America, and Australasia.

Patients receiving TMC435 were allowed to stop all treatment at week 24 when a) HCV RNA levels less then 25 IU/mL at week 4 and b) HCV RNA less then 25 IU/mL levels at weeks 12, 16 and 20. Patients who did not meet the above response-guided criteria continued with peg-interferon and ribavirin until Week-48.
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Majority Of Patients were undetectable at week 12
TMC435 demonstrated potent antiviral activity, at week 4 (rapid virologic response (RVR)) and at week 12 (complete early virologic response (cEVR)) HCV RNA was undetectable (less then 25IU/ml) for the majority of patients. The viral breakthrough rate was 4.9 percent in the TMC435 treatment groups.

(TMC435 is also being studied in HCV genotype-1 treatment-experienced patients who have failed treatment with peg-interferon and ribavirin. The ASPIRE study (Antiviral STAT-C Protease Inhibitor Regimen in Experienced patients; TMC435-C206; NCT00980330) is an ongoing global phase 2b randomized, double-blind, placebo controlled study in 463 patients)

Side Effects: The most common adverse events were headache and fatigue, 46 percent and 42 percent in the TMC435 groups and 51 percent and 47 percent in the placebo group respectively. There were no clinically significant differences in frequency of rash, anemia or gastrointestinal events between the TMC435 groups and placebo. Most AEs were mild to moderate in severity. AEs leading to treatment discontinuation were reported in 7.1 percent of patients in TMC435 arms and 7.8 percent in placebo arm. In laboratory parameters, significant decreases in transaminases (ALT and AST) were observed in all treatment groups. Small and transient bilirubin elevations (direct and indirect) were seen in the TMC435 150mg dose groups.

AASLD: TMC435 Rapid Response for Once-Daily Protease Inhibitor
AASLD:TMC435 PILLAR study in treatment-naive patients/ genotype 1


RG7128
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RG7128, being developed jointly by Roche and Pharmasset

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Background on non-nucleoside polymerase inhibitors "(non-nucs), and nucleoside polymerase inhibitors (nucs)".
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Excerpt
*From biopharma report:Both Vertex and Merck intend on launching new HCV treatments in 2011 based on a new class of compounds known as NS3 protease inhibitors (PI). These drugs herald a new breed of targeted medicines- sometimes called direct acting antivirals (DAA). The advantage is a significantly higher cure rate and shorter duration of treatment. However, these drugs are susceptible to viral resistance and require concurrent use with both interferon and ribavirin. A second type of compound focuses on inhibition of the NS5B polymerase. Of these there are two classes, non-nucleoside polymerase inhibitors (non-nucs), and nucleoside polymerase inhibitors (nucs). Both have been shown to be effective in combination with interferon + ribavirin, but non-nucs, like protease inhibitors, are also prone to mutation driven resistance.
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On the other hand, nucleoside polymerase inhibitors have a high barrier to resistance. In studies shown by Roche, no resistance was observed in cultures treated with R7128, its nucleoside polymerase inhibitor licensed from Pharmasset, for two weeks as monotherapy. Cultures treated with non-nucs or protease inhibitors all developed resistance. R7128 was also shown to reduce the formation of resistant colonies when added to either a non-nuc or PI. These studies show the flexibility of nucs in combination treatment.

...
Pharmasset’s lead compound is currently in multiple Phase II trials. Results from the 12 week R7128 treatment portion of a 48 week triple combo PROPEL trial with interferon + ribavirin trial have been released showing high rapid virologic responses and a low rate of adverse events. Full SVR data will be available in 2011. A longer trial involving 24 weeks of dosing called JUMP-C is now dosing. Phase III studies are expected to begin in 2011 as well, with an NDA filing anticipated in 2013.
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PROPEL trialRG7128 plus peginterferon (pegIFN) alfa-2a with ribavirin (RBV) demonstrated high rapid virologic response (RVR) and complete early virologic response (cEVR) rates in treatment-naive patients with genotype 1 or 4 HCV infection
.RG7128 had safety profile similar to standard of care
RG7128 not associated with treatment-emergent viral breakthrough or resistance
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INFORM-1 Trial
Roche is conducting a combination trial of R7128 with the protease inhibitor R7227=( also known as Danoprevir/ITMN-191) from Intermune. Results from a 14 day INFORM-1 trial showed the drugs were safe when administered together and resulted in a sustained viral load reduction. Continuing studies will add the drug Ritonavir to boost R7227 without increasing side effects
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From Doctors Guide: INFORM-1 trial was designed to assess the safety, tolerability, and antiviral activity of an oral combination treatment with 2 experimental drugs, RG7128 (a polymerase inhibitor that blocks elongation of the new HCV RNA chain) and danoprevir (also known as R-7227/ITMN-191) (a protease inhibitor that blocks an enzyme the virus needs to replicate itself) in patients with chronic HCV.A total of 88 patients with HCV genotype 1 were recruited into 1 of 7 treatment groups and randomised to receive various doses and schedules of the combined treatment (n = 74) or placebo (n = 14) for up to 13 days. Some patients had never been treated before, while others had failed interferon-based standard therapy.
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Change in HCV RNA concentration was measured at the start of the study and at regular intervals during treatment up to day 14.
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Patients who had never been treated before who received the highest doses of the 2 drugs (1000 mg RG7128 and 900 mg danoprevir BID) had a median HCV RNA reduction after 14 days of 5.1 log10 IU/ml, compared with a reduction of 4.9 log10 IU/ml in patients who had shown no response to previous standard treatment, and an increase of 0.079 log10 IU/ml in patients taking placebo.The combined treatment of RG7128 and danoprevir was generally well tolerated with no treatment-related severe side-effects, and no safety-related treatment discontinuations.In addition, there was no evidence of treatment resistance, unlike the rapid development of resistance shown by some classes of direct-acting antiviral drugs when given as monotherapy.
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The balance of Pharmasset’s HCV pipeline consists of PSI-7977, which is enrolling patients in Phase IIb and PSI-938, which has completed Phase 1b. The company is planning studies combining these two nucs; initial data should be available Q1 next year. Phase II combo studies are expected to begin around the second or third quarter of 2011
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Pharmassets candidates nearing preparation for clinical development:
RG7128, a pro-drug of PSI-6130 for the treatment of HCV, is entering a phase 2b clinical trial through a collaboration with Roche;
PSI-7977, an isomer of PSI-7851 is a nucleotide analog for the treatment of HCV, and is currently in a phase 2b trial;
PSI-352938 (PSI-938), a purine nucleotide analog for the treatment of HCV, recently completed a phase 1 trial.
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Slide Presentations:
JG. McHutchinson et al61st Annual Meeting of the American Association for the Study of Liver DiseasesBoston, MAOct 29-Nov 2, 2010
Clinical synergy of an anti-HCV nucleotide analog with SOC: Viral kinetics of PSI-7977 with SOCE. Lawitz et al61st Annual Meeting of the American Association for the Study of Liver DiseasesBoston, MAOct 29-Nov 2, 2010
High Rapid Virologic Response (RVR) with PSI-7977 daily dosing plus PEG-IFN/RBV in a 28-day Phase 2a trial
E. Lawitz et al61st Annual Meeting of the American Association for the Study of Liver DiseasesBoston, MAOct 29-Nov 2, 2010
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Danoprevir
Danoprevir= (RG7227 formerly R7227 also known as ITMN-191) is a investigational protease inhibitor, which targets the hepatitis C virus, used in combination with the standard of care for HCV infection; peg-interferon alpha-2a and ribavirin. It has demonstrated rapid and profound reductions in HCV RNA.

Roche Acquired the rights to InterMune HCV Protease Inhibitor Danoprevir
.*Excerpt:
From Medscape: The investigational protease inhibitor danoprevir, which targets the hepatitis C virus (HCV), combined with the standard of care for HCV infection — peg-interferon alpha-2a and ribavirin — produces rapid and profound reductions in HCV RNA.
.Entry criteria were noncirrhotic treatment-naïve adults (predominately genotype 1 virus) with serum HCV RNA levels of 50 000 IU/mL or more and without advanced fibrosis.
.All patients were administered a standard of care regimen of pegylated interferon alpha-2a plus weight-based ribavirin, and were randomized, for 12 weeks, to placebo or 1 of 3 danoprevir groups: 300 mg every 8 hours, 600 mg every 12 hours, or 900 mg every 12 hours. When danoprevir was stopped, all patients continued on standard therapy for an additional 24 or 48 weeks, depending on whether or not they achieved a rapid virologic response
.The second part of the study was a planned continuation of danoprevir to week 24, but that "never was undertaken" because of incidents of reversible grade 4 ALT elevations in 3 patients in the 900 mg group, the highest dose of the study, said Dr. Terrault. Patients already enrolled in the 900 mg group were rerandomized to 300 or 600 mg.
.The principle measure of efficacy was an undetectable HCV RNA level (less then 15 IU/mL); measurements were taken at baseline and at weeks 2, 4, and 12. Missing data points were considered to be nonresponders.
.Dr. Terrault reported that the interim analysis of those who completed 12 weeks of danoprevir therapy was based on 62 patients receiving 300 mg (93%), 61 receiving 600 mg (94%), and 8 receiving 900 mg (16%).
At week 2, levels of HCV RNA were undetectable in 52% of the 300 mg group, 57% of the 600 mg group, 62% of the 900 mg group, and 0% of the placebo group.
At week 4, that progressed to 73%, 86%, 86%, and 7%, respectively; and at week 12, to 88%, 89%, 92%, and 43%.
.Viral resistance to danoprevir emerged in the low-dose (300 mg) group in 2 patients at week 2 and in 5 patients at weeks 4 and 12. In the 600 mg group, patients fared better, with 3 developing treatment-emergent resistance by week 12. No patients developed resistance in the highest-dose (900 mg) group, but the cumulative exposure was significantly less because of the emerging toxicity and discontinuation of that dosing regimen. All of the resistance was seen in patients with HCV genotype 1a.
.Side Effects
Rates of most common adverse events in the danoprevir groups were at least twice as high as those seen with standard care alone. Often, there was little difference in the incidence of adverse effects with an increase in the dose of danoprevir.Although the serious adverse event of grade 4 ALT elevation was most likely to occur at the highest dose of the drug (3 incidents) and led to the discontinuation of that dosing, there also was 1 incident among the 60 patients in the 600 mg group. Dr. Terrault said that "modeling the available pharmacokinetics data showed a relationship between danoprevir exposure, specifically AUC and the likelihood of having ALT elevation."
.AASLD:HCV Protease Inhibitor Danoprevir is Positive

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BMS-790052 and BMS-650032
BARACLUDE, BMS-790052, and BMS-650032 were discovered by Bristol-Myers Squibb Research and Development. PEG-Interferon lambda was discovered by ZymoGenetics, Inc. Bristol-Myers Squibb and ZymoGenetics announced a global collaboration for PEG-Interferon lambda and its related development program in 2009. In September 2010, Bristol-Myers Squibb announced its intent to acquire ZymoGenetics.

*Excerpt: Combination therapy with BMS-790052 and BMS-650032 alone or with pegylated interferon and ribavirin (pegIFNα/RBV) results in undetectable HCV RNA through 12 weeks of therapy in HCV genotype 1 null responders.
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Study Objective:
To assess the safety and antiviral activity of BMS-790052 and BMS-650032 alone or combined with pegIFNα/RBV in patients with HCV genotype 1 who have not responded to prior standard of care treatment (null responders)
Materials and Methods
Patients in Group A were treated with BMS-790052 and BMS-650032. Patients in Group B were treated with BMS-790052, BMS-650032 and pegIFNα/RBV. The response rates for both treatment groups are as follows
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One patient in Group B did not meet cEVR; however, on retesting the patient’s viral load was undetectable.** Viral breakthrough was defined as a) any increase in HCV RNA more then 1 log10 from nadir, or b) any detectable HCV RNA more then 25 IU/mL on or after week 4, or c) any detectable HCV RNA less then 25 IU/mL on or after week 4 confirmed by retesting.
Study Conclusion:
Seven out of 11 patients receiving BMS-790052 and BMS-650032 without pegIFNα/RBV achieved rapid virologic response, defined as undetectable viral load by week 4. However, viral breakthrough occurred in six of the 11 patients in this treatment group. Nine out of 10 patients receiving the combination of BMS-790052, BMS-650032 and pegIFNα/RBV achieved complete early virologic response (cEVR), defined as undetectable viral load by week 12.
Side Effects:
Two patients experienced a severe (Grade 3 or 4) adverse event – one patient in Group A experienced fatigue and one patient in Group B experienced low white blood cell count (neutropenia). There was no discontinuation of BMS study drugs due to adverse events (AEs).
AEs were mainly mild to moderate in severity. The most common AEs (more than three occurrences) across both study groups were:

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Lambda Pegylated Interferon
PEG-IFN-lambda is one of several molecules Bristol-Myers Squibb is studying for the potential treatment of hepatitis C..
The EMERGE study is a two-part, randomized, controlled, multicenter phase II, phase II study of PEG-IFN lambda in treatment-naïve patients with chronic hepatitis C genotype 1, 2, 3 or 4. ...
To assess the safety and antiviral activity of four fixed doses of PEG-IFN-lambda in treatment-naïve patients with HCV genotypes 1, 2, 3, and 4
.These data are from the first part of the EMERGE study. In this ongoing, open-label Phase IIa study, 55 patients were randomized to receive PEG-IFN-lambda at one of four dose levels (80, 120, 180 or 240 mg) or PEG-IFN-alpha at 180 μg.
Patients received PEG-IFN lambda and PEG-IFN alpha administered subcutaneously on a weekly basis, as well as ribavirin on a daily basis, dosed according to HCV genotype and body weight. Patients with HCV genotype 2 or 3 were studied for up to 24 weeks; patients with genotype 1 or 4 were studied for up to 48 weeks.
.Study Conclusion:
At PEG-IFN-lambda’s three highest dosing levels (120 mcg, 180 mcg, 240 mcg), virologic response at 4 and 12 weeks was similar to or greater than that observed and reported with standard interferons (PEG-IFN-alpha).
Adverse events were mild to moderate in severity and led to few treatment discontinuations.
.
.Genotypes 1 or 4

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Genotypes 2 or 3




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Side Effects
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BI-201335/BI 207127
The Boehringer Ingelheim group who is developing BI-201335, BI 207127 is located in Ingelheim, Germany.
*They are now in Phase Ib deemed "SOUND-C1". Planning is currently underway to begin Phase II trials of BI 207127 with BI 201335 in interferon-sparing regimens both with and without ribavirin.
BI 201335 is an investigational oral HCV NS3/4A protease inhibitor, discovered from Boehringer Ingelheim’s own research and development, which has completed clinical trials through Phase IIb (SILEN-C studies). This Phase II program supports the investigation of BI 201335 in Phase III trials. BI 207127 is an NS5B RNA-dependent polymerase inhibitor that has completed Phase I clinical trials.
Boehringer Ingelheim Oral Hepatitis C Protease Inhibitor and Polymerase Inhibitor Combination Shows Rapid Viral Response without Use of Pegylated Interferon
*Excerpt:
The Phase Ib study, SOUND-C1, showed the combination of two oral hepatitis C virus (HCV) compounds, the protease inhibitor BI 201335 and the polymerase inhibitor BI 207127, with ribavirin reduced viral load to the lower limit of quantifiable levels in HCV treatment-naïve patients. The regimen did not include interferon through the first 28 days of treatment
New protease-polymerase inhibitor combination resulted in 73-100% rapid virological responses without pegylated interferon. In this randomised open-label trial, 32 treatment-naïve genotype-1 HCV patients received a combination of BI 207127 in either 400mg or 600mg doses three times a day (TID) with BI 201335 120mg once daily (QD) together with ribavirin (RBV) (1000/1200mg daily in two doses) for 28 days.
All patients had a rapid and sharp decline in HCV viral load during the first two days, followed by a slower second phase decline. In the lower and higher dose groups, 73 and 100% of patients achieved a rapid virological response (i.e. had a HCV RNA below thelower limit of quantification after 4 weeks of treatment).
One patient experienced a viral breakthrough (increase by more then 1 LOG10 from nadir during treatment) and one other experienced a 0.7 LOG10 increase in viral load. Both patients were in the lower dose group of BI 207127 and were patients with a high baseline viral load. On day 29, all patients were switched to treatment with BI 201335 and PegIFN/RBV for an additional 44 weeks per the defined study protocol, and will be followed to evaluate sustained virological response.
“These early data suggest that there is the potential for the combination of oral anti-HCV therapies to reduce the viral load in a more tolerable, interferon-sparing regimen.
Side Effects:The PegIFN sparing treatment was well tolerated. Investigators reported that the most common adverse events observed in the study were mild gastro-intestinal effects (diarrhea, nausea, vomiting), rash or photosensitivity. Laboratory parameters did not indicate any relevant changes from baseline, except for a continuous drop in amino alanine transferase (ALT) in all patients, a decrease of hemoglobin (median -1.7 and -2.6 g/dL) and an increase of unconjugated bilirubin (median +9.8 and +11.5 umol/L) similar to reported results from earlier BI 201335 trials. There were no serious or severe adverse events and no discontinuations due to adverse events reported in the study during treatment with BI 207127 and BI 201335. A phase IIb trial testing different dose regimens of this combination with longer durations is planned to evaluate sustained virological response rates
Strong antiviral activity and safety of IFN-sparing treatment with the protease inhibitor BI 201335, the HCV polymerase inhibitor BI 207127, and ribavirin, in patients with chronic hepatitis C:
The SOUND-C1 trial
The drugmaker Abbott and its investigational drug ABT-450 is used along with NORVIR® (ritonavir) for the treatment of HCV . "NORVIR is in a class of medicines called the HIV protease (PRO-tee-ase) inhibitors. NORVIR is used in combination with other anti-HIV medicines to treat people with human immunodeficiency virus (HIV) infection. NORVIR is for adults and for children age greater than 1 month and older."
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*Excerpt :
Abbott and Enanta Pharmaceuticals had positive results from a Phase 2 study of ABT-450/r, an investigational, oral protease inhibitor being developed for the treatment of hepatitis C (HCV) infection. Initial 3-day and 4-week results suggest that ABT-450/r (ABT-450 with 100mg of ritonavir to support once-daily dosing) demonstrates potent antiviral activity in genotype 1 treatment-naïve adults.
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Results show that more than 90 percent of patients (21 of 23) on study drug achieved HCV-RNA levels less then 25 IU/mL at four weeks. Results were presented at the AASLD.
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Key findings:-- After three days, treatment with ABT-450/r alone resulted in statistically significant, 4-log mean reductions of HCV RNA, across the three dose ranges of ABT-450 (50mg, 100mg, 200mg, once-daily dosing) compared to placebo--
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At week four, 91.3 percent (21 of 23) of patients receiving ABT-450/r in combination with standard of care (SOC) pegylated alpha interferon and ribavirin (pegIFN/RBV) achieved HCV-RNA less then 25 IU/ml--
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Safety appears consistent to that expected with SOC
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"ABT-450 was discovered as part of an alliance between Abbott and Enanta and is being developed with low-dose ritonavir, which enhances the pharmacokinetic properties of ABT-450, allowing for once-daily dosing. This Phase 2 study also evaluated ABT-333 and ABT-072, two of Abbott's internally discovered compounds that are part of the company's ongoing non-nucleoside polymerase inhibitor development program. The study findings for these two compounds have been submitted for presentation at a future scientific meeting."
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*See Slides @ NATAP Initial Antiviral Activity of the HCV NS3 Protease Inhibitor ABT-450 When Given with Low-dose Ritonavir as 3-Day Monotherapy: Preliminary Results of Study M11-602 in Genotype 1 (GT1) HCV-infected Treatment-naïve Subjects
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ANA598
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Anadys investigational polymerase inhibitor ANA598 was studied in treatment-naive patients with genotype-1, used in combination with standard HCV therapy.
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*Excerpt:
From Medpage: Adding the investigational polymerase inhibitor ANA598 to standard care speeded up the clearance of hepatitis C, compared with standard care alone, a researcher reported here.
.An ongoing double-blind, placebo-controlled phase II trial among more than 100 patients, found that after 12 weeks of therapy with one of two doses of ANA598, 73% and 75% of patients had undetectable levels of hep C virus, depending on dose, according to Eric Lawitz, MD, of Alamo Medical Research in San Antonio, Texas.
.In contrast, 63% of those getting only standard care with pegylated interferon alpha-2a and ribavirin had undetectable hep C levels, Lawitz said at the annual meeting of the American Association for the Study of Liver Diseases.
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To examine the efficacy and safety of the compound, he and colleagues enrolled 105 treatment-naive patients with genotype-1 virus and randomly assigned them to either 200 or 400 mg of ANA598 twice a day, or to placebo. Those getting active drug also had a loading dose of 800 mg on the first day of therapy.
.All of the trial patients also got standard treatment with pegylated interferon alpha-2a and ribavirin.
.Patients with undetectable hep C virus at weeks four and 12 weeks, Lawitz explained, were re-randomized to continue standard care for another 12 or 32 weeks.
.There was little difference between the two arms in terms of the speed at which the drug cleared the virus, Lawitz said, but viral clearance was always faster than the standard care alone.
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Side Effects :The main difference between the two arms was in the adverse events. In the high-dose group "400 mg" 62% of the patients reported rash, including 17 with grade 1, one with grade 2, and three patients with grade 3 rash.
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PPI-461
Presidio's drug PPI-461 is a NS5A inhibitor PPI-461 exhibits activity against 1-7 HCV genotypes in laboratory assays.
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*Excerpt:
The pharmacokinetic results indicated that all subjects rapidly achieved substantial blood levels of PPI-461, which far exceeded the concentrations of PPI-461 needed to inhibit HCV (genotypes 1-7) in the laboratory. For PPI-461 doses of 50 mg or more, all subjects achieved blood levels of PPI-461 that would be expected to inhibit HCV replication for 24 hours or longer. This profile suggests that PPI-461 may be effective when administered to hepatitis C patients at relatively low oral doses on a once-daily dosing schedule, which would facilitate its convenient use in future co-formulated combination therapies
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First Study of PPI-461 in Hepatitis C Patients UnderwayBased on the encouraging Phase 1a results, Presidio has initiated a Phase 1b proof-of-concept clinical trial of PPI-461 in hepatitis C patients. This dose-ranging trial will evaluate the safety, pharmacokinetics and antiviral efficacy of PPI-461 in previously-untreated patients with HCV genotype-1 infection.
From NATAP : The new Merck also once-daily HCV protease MK5172 also looks very good: "Safety and Antiviral Activity of MK-5172, a Novel HCV NS3/4a Protease Inhibitor with Potent Activity Against Known Resistance Mutants, in Genotype 1 and 3 HCV-Infected Patients".
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The protease has activity against genotype 1 and 3. Multiple oral doses of 400 mg MK-5172 qd for 7 days were generally well tolerated in HCV-infected patients. Mean maximum reductions from baseline of HCV viral RNA (Ses) were 5.4 (0.21) and 3.98 (0.22) log10 IU/mL for GT 1 and 3, respectively.

AASLD: Safety and Antiviral Activity of MK-5172, a Novel HCV NS3/4a Protease Inhibitor with Potent Activity Against Known Resistance Mutants, in Genotype 1 and 3 HCV-Infected Patients

M11-602From NATAP Preliminary Results of Study M11-602 in Genotype 1 (GT1) HCV-infected Treatment-naïve Subjects" Abbott also reported 4 weeks data in a poster here in combination with peg/rbv. Subjects were randomized to one of 3 doses of ABT-450/r (50/100 mg, 100/100 mg or 200/100 mg) or placebo once daily for 3 days, followed by ABT-450/r or placebo in combination with standard of care (SOC) consisting of pegylated interferon alfa-2a 180 µg/week + weight-based ribavirin 1000-1200 mg/day through week 1.
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.Merck Vaniprevir MK-7009 protease inhibitor
Idera Pharmaceuticals data on IMO-2125 phase 1 trial.
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IMO-2125 is currently in a Phase 1 clinical trial in null-responder patients, defined as those who did not achieve a 2 log10 reduction with prior standard of care treatment, as monotherapy for 4 weeks. IMO-2125 is also being evaluated in a Phase 1 clinical trial in treatment-naive patients in combination with ribavirin for 4 weeks.
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From The Street : This Phase 1 clinical trial evaluated 51 null-responder HCV patients; 41 patients received IMO-2125 monotherapy at five dose levels and 10 patients received placebo once per week for four weeks. Most of these patients were infected with HCV genotype 1 and had the CT or TT IL28B gene alleles.
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IMO-2125 was well tolerated at all dose levels. IMO-2125 induced a broad immune response with dose-dependent increases in serum concentrations of antiviral proteins and activation of cellular immune responses.
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Across the three highest dose levels, 75% of patients achieved a 1 log10 or greater decrease in viral load at least once during the treatment period. Consistent with the proposed mechanism of IMO-2125, induction of higher serum concentrations of interferon-alpha correlated with greater decreases in HCV viral load. Additional patients are being enrolled in this Phase 1 trial to evaluate twice-weekly dosing of IMO-2125.
Inhibitex has initiated a Phase 1b, multiple ascending dose (MAD) clinical trial of INX-189, its nucleotide polymerase inhibitor in development for the treatment of chronic infections caused by hepatitis C virus (HCV).
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*Excerpt:
The trial, which is being conducted under an IND in the United States, is a double-blind, placebo-controlled, dose escalation study designed to evaluate the safety, tolerability, pharmacokinetics and anti-viral activity of INX-189 administered orally once daily for seven days in treatment naïve patients with HCV genotype 1.
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Each treatment cohort will include 10 patients, eight of which will receive INX-189 and two of which will receive placebo. The first cohort in the Phase 1b study will receive 9 mg of INX-189 once daily. In addition to evaluating INX-189 as monotherapy, the Company plans to evaluate two dose levels of INX-189 administered once daily for seven days in combination with ribavirin, which is one of the drugs currently approved for the treatment of HCV. The dose levels of INX-189 to be evaluated in combination with ribavirin will be determined based upon the results of the monotherapy cohorts.
Gilead's Investigational Hepatitis C Compounds GS 9190 and GS 9256 in treatment Naïve, genotype 1 HCV Subjects. Used in Combination with Standard of Care Therapies Achieve Substantial Viral Suppression in Phase II Study **See Links For Complete Information
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Excerpt: Gilead's three-arm Phase IIa trial (Study 196-0112) evaluated the safety and efficacy of GS 9190, an oral polymerase inhibitor, in combination with GS 9256, an oral protease inhibitor, when used as:
1) a dual antiviral therapy alone
2) a three-drug regimen with RBV
3) a four-drug regimen with RBV and Peg-IFN.
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The study found that the all-oral regimen of GS 9190, GS 9256 and RBV produced substantial viral suppression, with a median maximal decline from baseline in HCV RNA of 5.1 log10 IU/mL during 28 days of treatment.
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Among patients given the four-drug regimen of GS 9190, GS 9256, RBV and Peg-IFN, 100 percent (14/14 patients) achieved Rapid Virologic Response (RVR) (HCV RNA less then 25 IU/mL) at day 28, with 93 percent (13/14 patients) achieving undetectable viral levels (HCV RNA less then 10 IU/mL). No virologic breakthroughs were observed in this arm
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Gilead HCV Pipeline Research In addition to Study 196-0112, data from seven additional studies will be presented at The Liver Meeting highlighting the clinical profile of the company's other HCV pipeline candidates, including another protease inhibitor, GS 9451, and a novel NS5A inhibitor, GS 5885. Gilead's HCV pipeline now includes seven unique molecules spanning six therapeutic classes with different mechanisms of action. Five of these compounds are currently in clinical trials, and two are slated to enter human clinical studies early next year.
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Side Effects: The majority of adverse events were Grade 1 or 2 in severity and resolved with continued treatment. The most common adverse events observed in each of the three arms were headache, diarrhea and nausea. Some patients taking the three-drug combination also experienced fatigue and insomnia, and some patients taking the four-drug combination experienced influenza-like illness, fatigue, myalgia and cough. There were two serious adverse events including one case of bursitis and a hospitalization for vasovagal collapse (fainting), which was attributed to gastroenteritis and occurred in a patient who continued therapy and achieved RVR. Elevations in bilirubin were observed across all three study arms, the majority of which were Grade 1 or 2 in severity and none of which resulted in study drug discontinuation.
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GI-5005
GlobeImmune Expands GI-5005-02 Phase 2b Trial to Include Additional Treatment Naive IL28B T/T Subjects With Chronic Genotype 1 HCV
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Phase 2b Study Demonstrates GlobeImmune's GI-5005 HCV Therapeutic Vaccine Increases Sustained Virologic Response by 12 Percent in Patients Who Previously Failed Therapy With Standard of Care
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Results in both subgroups were similar to the overall outcome but did not reach statistical significance compared with standard care, Pockros told a late-breaker session at the annual meeting of the American Association for the Study of Liver Diseases. But the findings, based on just 133 patients, are enough to justify continued development of the vaccine, Pockros said, including tests to see if it can be effective without the standard hepatitis C treatment regimen, which has difficult side effects.
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Excerpt:
On an intent-to-treat basis (subjects who received at least one dose of combination therapy), prior non-responders receiving GI-5005 plus SOC as a triple therapy had an SVR rate of 17%, compared to an SVR rate of only 5% in patients receiving SOC alone. Prior non-responders in this study were defined as patients who did not clear virus after a minimum of 12 weeks of SOC, including null responders, poor responders, and partial responders. Relapsers and on-treatment breakthroughs were not enrolled in the study. The most common adverse events associated with GI-5005 were injection site reactions that were generally mild and transient in nature. Discontinuation rates due to adverse events in the GI-5005 triple therapy arm were comparable to the discontinuation rates in the SOC alone arm.
."Only 4-7% of patients with genotype 1 HCV who were null, poor or partial responders to their first course of pegylated interferon-based therapy would be expected to achieve a sustained virologic response with a second course of treatment," said Dr. Pockros. "In this study, GI-5005 conferred a three-fold improvement in SVR, an important treatment effect in this challenging patient population."
.Additional immunology data from the study will be presented in a poster on Tuesday, November 2, 2010 by John M. Vierling, M.D., of Baylor College of Medicine. These data show that GI-5005 improved HCV-specific T cell responses 10-fold over SOC alone in patients with the IL28B T/T genotype (~20% of chronically infected patients), the subgroup most likely to fail treatment with SOC alone.
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Additional AASLD News
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