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Hepatitis C New Drugs Review
FDA approved Incivek(telaprevir, Vertex) on Monday 23 May by its PDUFA deadline.A paradigm shift in the treatment of Hepatitis C virus infection. http://knol.google.com/k/krishan-maggon/boceprevir-merck-telaprevir-vertex/3fy5eowy8suq3/151#
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Created public version #121 of the knol: "Boceprevir (Merck) & Telaprevir (Vertex) Hepatitis C : FDA Review & Approval"

Created public version #121 of the knol: "Boceprevir (Merck) & Telaprevir (Vertex) Hepatitis C : FDA Review & Approval" | Hepatitis C New Drugs Review | Scoop.it
Krishan Maggon published version 121 of a knol titled: "Boceprevir (Merck) & Telaprevir (Vertex) Hepatitis C : FDA Review & Approval"...
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Express Scripts Shuns Gilead in Hepatitis C Deal With AbbVie

Express Scripts Shuns Gilead in Hepatitis C Deal With AbbVie | Hepatitis C New Drugs Review | Scoop.it
AbbVie Inc. (ABBV) agreed to make its hepatitis C drug the exclusive treatment for most patients covered by Express Scripts Holding Co. (ESRX)’s main formulary, a blow against rival Gilead Sciences Inc. (GILD) and a move that will escalate the debate over drug prices and insurance benefits.
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Big pharmacy players are going to determine who leads the HCV market?

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Hep-C-Report-2014-Stepping-Stones.pdf

These successes emerged from many unsuccessful research attempts over the years. Between 1998 and 2014 alone there were 77 investigational medicines that failed in clinical
trials. Setbacks in biopharmaceutical research are inevitable but also necessary as stepping stones to help researchers understand effective pathways for targeting and treating disease. These so-called “failures” paved the way for the 12 new medicines approved by the U.S. Food and Drug Administration over the same period which have ushered in a new era
of treatment of hepatitis C.


Hepatitis C research successes have built over time. Following the identification of the virus in 1989, stepwise improvements in interferon-based therapy ensued over the next two decades. Simultaneously, researchers were applying lessons learned from successes in the treatment of HIV/AIDS and began exploring similar modes of action against the hepatitis C virus. After years of research and many setbacks, the first of these medicines—
called “direct-acting antivirals”—were approved in 2011. Since that time, many more of these medicines have been approved and researchers are finding even greater success in
employing a combination of antiviral therapies to more effectively combat the disease.


Today, there are 75 medicines to treat hepatitis C in development in the United States. These medicines promise to improve cure rates further, reduce side effects and duration of treatment, and expand treatment options. The future is truly hopeful for patients with
hepatitis C.

Krishan Maggon 's insight:

Tremendous research advances in recent years are transforming treatment of this debilitating disease. Today, more than 90% of patients with the most common form of the disease can expect to be cured in as little as 8 weeks with newly approved antiviral therapies. This stands in stark contrast to cure rates of 41% over 48 weeks with severe side effects for the same patients just over a decade ago.

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FDA approves Viekira Pak ((ombitasvir, paritaprevir, ritonavir, dasabuvir tablets, AbbVie) to treat hepatitis C

FDA approves Viekira Pak ((ombitasvir, paritaprevir, ritonavir, dasabuvir tablets, AbbVie)  to treat hepatitis C | Hepatitis C New Drugs Review | Scoop.it

The U.S. Food and Drug Administration today approved Viekira Pak (ombitasvir, paritaprevir and ritonavir tablets co-packaged with dasabuvir tablets) to treat patients with chronic hepatitis C virus (HCV) genotype 1 infection, including those with a type of advanced liver disease called cirrhosis.

 

Viekira Pak contains three new drugs—ombitasvir, paritaprevir and dasabuvir—that work together to inhibit the growth of HCV. It also contains ritonavir, a previously approved drug, which is used to increase blood levels of paritaprevir. Viekira Pak can be used with or without ribavirin, but it is not recommended for patients whose liver is unable to function properly (decompensated cirrhosis).

 

 

Viekira Pak’s efficacy was evaluated in six clinical trials enrolling 2,308 participants with chronic HCV infection with and without cirrhosis. In different trials, participants were randomly assigned to receive Viekira Pak or placebo (sugar pill); Viekira Pak with or without ribavirin; or Viekira Pak with ribavirin for 12 or 24 weeks.

The trials were designed to measure whether the hepatitis C virus was no longer detected in the blood at least 12 weeks after finishing treatment (sustained virologic response, or SVR), indicating that a participant’s HCV infection has been cured. Results from multiple populations, including those considered difficult to treat, showed 91 to 100 percent of participants who received Viekira Pak at the recommended dosing achieved SVR. The recommended dosing for Viekira Pak is two ombitasvir, paritaprevir, ritonavir 12.5 milligrams (mg)/75 mg/50 mg tablets once daily and one dasabuvir 250 mg tablet twice daily.

The most common side effects reported in clinical trial participants were feeling tired, itching, feeling weak or lack of energy, nausea and trouble sleeping.

 

 

Krishan Maggon 's insight:

AbbVie has priced the new 4 drug tablet regiment at 12% discount to Gilead Sovaldi, $83320 for 12 weeks therapy. The inconvience of patients taking so many pills a day vs only a single pill

 

 

 

Viekira Pak is the fourth drug product approved by the FDA in the past year to treat chronic HCV infection. The FDA approved Olysio (simeprevir) in November 2013, Sovaldi (sofosbuvir) in December 2013 and Harvoni (ledipasvir and sofosbuvir) in October 2014.

 

Viekira Pak is marketed by AbbVie Inc., based in North Chicago, Illinois. Olysio is marketed by Raritan, New Jersey-based Janssen Pharmaceuticals. Sovaldi and Harvoni are marketed by Gilead Sciences, based in Foster City, California.

 

Viekira Pak is the eleventh new drug product with breakthrough therapy designation to receive FDA approval. The FDA can designate a drug as a breakthrough therapy at the request of the sponsor if preliminary clinical evidence indicates the drug may demonstrate a substantial improvement over available therapies for patients with serious or life-threatening diseases. Viekira Pak was reviewed under the FDA’s priority review program, which provides for an expedited review of drugs that treat serious conditions and, if approved, would provide significant improvement in safety or effectiveness.

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Nonstructural Protein 5A (NS5A) and Human Replication Protein A Increase the ... - Journal of Virology

Using a rolling-circle RNA template, we have reconstituted an in vitro HCV replication system that allows us to interrogate the role of viral and host proteins in HCV replication and delineate the molecular interactions. We showed that HCV NS5A(S25-C447) and cellular replication protein A (RPA) functionally cooperate as a processivity factor to stimulate HCV replication by HCV NS5BΔ21 polymerase and NS3 helicase. This system paves the way to test other proteins and may be used as an assay for discovery of HCV inhibitors.

Krishan Maggon 's insight:
Accepted manuscript posted online 15 October 2014, doi:10.1128/JVI.01677-14                                                                J. Virol. January 2015 vol. 89no. 1 165-180Nonstructural Protein 5A (NS5A) and Human Replication Protein A Increase the Processivity of Hepatitis C Virus NS5B Polymerase Activity In VitroNagraj Mania, Alexander Yuzhakova, Olga Yuzhakova, Joyce T. Collb, Jim Blackb,Kumkum Saxenab, John R. Fulghumb, Judith A. Lippkeb, B. Govinda Raoc*,Rene Rijnbranda and Ann D. Kwonga*
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Hepatitis C Linked to Accelerated Immune Cell Differentiation

Hepatitis C Linked to Accelerated Immune Cell Differentiation | Hepatitis C New Drugs Review | Scoop.it
Hepatitis C is linked to accelerated differentiation of CD4 and CD8 cells—major building blocks of the immune system—into specific phenotypes.

 

 HCV-positive had 25 percent fewer naive CD4 cells, 33 percent more EM cells, and 37 percent fewer central memory CD8 cells when compared with those who did not have HCV. The coinfected group, however, only had one such association: a higher percentage of EM CD4 cells when compared with those monofinfected with HIV.  This particular link was restricted to individuals with fewer than 500 CD4 cells per microliter, which likely indicates a diminished immune system resulting from more advanced (and untreated) HIV disease. Additionally, among the coinfected set, the only link between hep C and higher percentages of activated CD4s and Tregs was among those with 500 or fewer CD4s.

Thus, while hep C was linked with accelerated immune cell differentiation, coinfection with HIV made the various related links less clear-cut.

Krishan Maggon 's insight:
Association of Chronic Hepatitis C Infection With T-Cell Phenotypes in HIV-Negative and HIV-Positive Women

Kuniholm, Mark H. PhD*; Xie, Xianhong PhD*; Anastos, Kathryn MD*,†; Kaplan, Robert C. PhD*; Xue, Xiaonan PhD*; Kovacs, Andrea MD‡; Peters, Marion G. MD§; Seaberg, Eric C. PhD‖; French, Audrey L. MD¶; Young, Mary A. MD#; Augenbraun, Michael MD**; Martinson, Jeffrey A. BA††; Bush, Kristin A. MS††; Landay, Alan L. PhD††,‡‡; Strickler, Howard D. MD, MPH*

 

JAIDS Journal of Acquired Immune Deficiency Syndromes:1 November 2014 - Volume 67 - Issue 3 - p 295–303doi: 10.1097/QAI.0000000000000310Clinical Science
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CA panel: Gilead's Harvoni cost-effective at $95K, but only affordable at half ... - FiercePharma

CA panel: Gilead's Harvoni cost-effective at $95K, but only affordable at half ... - FiercePharma | Hepatitis C New Drugs Review | Scoop.it
A California cost-effectiveness panel is prepared to say this about Gilead Sciences' brand-new combination treatment for hepatitis C: It's cost-effective, even at an eye-popping price. But--and this is a big but--the state can't afford to pay it.
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Gilead AbbVie Are Set To Split The $15 Billion Hepatitis C Market

Gilead  AbbVie Are Set To Split The $15 Billion Hepatitis C Market | Hepatitis C New Drugs Review | Scoop.it
A recent report by Morgan Stanley predicts a greater than 40 percent growth in the Hepatitis C (HCV) market in 2015. Projections indicate that the HCV market could be worth $15 billion in upcoming years, ...
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WIPO Seminar: For Access To Hepatitis C Treatments, Look At HIV Lessons - Intellectual Property Watch

WIPO Seminar: For Access To Hepatitis C Treatments, Look At HIV Lessons - Intellectual Property Watch | Hepatitis C New Drugs Review | Scoop.it
A seminar on innovation and access to medicine last week examined the issue of access to hepatitis C treatment, looking at the HIV/AIDS path. Voluntary licences, such as the one entered by Gilead f...
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European Medicines Agency - Find medicine - Harvoni

European Union agency responsible for the protection of public and animal health through the scientific evaluation and supervision of medicines.
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Harvone  EPAR, Product summary and Risk Management plan.

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Bristol-Myers Squibb Foundation awards nine grants to support care for high-risk patients with hepatitis B and C in China and India

Bristol-Myers Squibb Foundation awards nine grants to support care for high-risk patients with hepatitis B and C in China and India | Hepatitis C New Drugs Review | Scoop.it
World Pharma News - one of the world's leading web-based pharmaceutical news publications - is committed to providing and disseminating the most prominent pharmaceutical news and achievements.
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Mean annual cost of patients hospitalized for chronic hepatitis C in France: the HEPC-LONE study

Mean annual cost of patients hospitalized for chronic hepatitis C in France: the HEPC-LONE study | Hepatitis C New Drugs Review | Scoop.it
OBJECTIVE: To assess the mean annual cost of patients hospitalized for Chronic Hepatitis C, stratified by liver disease stage. METHOD: Hospital stays with ICD-10 code of chronic viral hepatitis C (B18.2) as principal, related or significantly
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The mean annual cost was 1100 Euro per patient in France. It was before the introduction of newer HCV antivirals combo therapies with 95-99% cure rates.

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Liver Cancer Sex differences: Luck of the chromosomes : Nature : Nature Publishing Group

Liver Cancer Sex differences: Luck of the chromosomes : Nature : Nature Publishing Group | Hepatitis C New Drugs Review | Scoop.it

A multitude of well-studied factors influence a person's susceptibility to cancer — genetic background, chemical exposure, diet and behaviour all contribute. But one factor that seems to play a major part in malignancy has received surprisingly short shrift from scientists: whether someone is male or female.

 

 

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Krishan Maggon 's curator insight, December 4, 4:06 AM

Liver cancer strikes many more men than women — finding out why could lead to new ways of preventing the disease.

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Achillion shares soar as potential treatment seen as 1 month hep C cure

Achillion shares soar as potential treatment seen as 1 month hep C cure | Hepatitis C New Drugs Review | Scoop.it
Dec 22 (Reuters) - Achillion Pharmaceuticals Inc said it would test a combination of two of its experimentalhepatitis C drugs after they showed promise against the virus inseparate studies.The biotechnology

 

The biotechnology company's shares shot up about 60 percent to $22.76 in premarket trading on Monday.

 

The first study, testing a combination of 50 mg of Achillion's ACH-3102 and 400 mg of Gilead Sciences Inc's Sovaldi, showed the regimen sustained a cure in patients for four weeks following therapy.

Krishan Maggon 's insight:

A 4 week cure  vs current 8-12 weeks is going to be a market winner.

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AbbVie Receives U.S. FDA Approval of VIEKIRA PAK™ (Ombitasvir/Paritaprevir/Ritonavir Tablets; Dasabuvir Tablets) for the Treatment of Chronic Genotype 1 Hepatitis C - Dec 19, 2014

AbbVie Receives U.S. FDA Approval of VIEKIRA PAK™ (Ombitasvir/Paritaprevir/Ritonavir Tablets; Dasabuvir Tablets) for the Treatment of Chronic Genotype 1 Hepatitis C - Dec 19, 2014 | Hepatitis C New Drugs Review | Scoop.it
For members of the media and job seekers, this page provides easy access to AbbVie media and press contacts via various channels.
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Harvoni (Gilead) costs $1125 per pill and is about to shatter sales records- Washington Post (blog)

Harvoni (Gilead) costs $1125 per pill and is about to shatter sales records- Washington Post (blog) | Hepatitis C New Drugs Review | Scoop.it
Amid concerns over drug prices, a pricey new hepatitis C treatment is taking off.
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Battle In Hepatitis C Market: Bristol-Myers Squibb Needs To Speed Up - Trefis

Battle In Hepatitis C Market: Bristol-Myers Squibb Needs To Speed Up - Trefis | Hepatitis C New Drugs Review | Scoop.it
The market for Hepatitis C drugs is hot, thanks to Gilead Sciences' breakthrough drug Sovaldi.
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Ombitasvir and Dasabuvir with Ribavirin for Hepatitis C with Cirrhosis

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Pharmacokinetics and Pharmacodynamics of Setrobuvir, an Orally Administered Hepatitis C Virus Non-Nucleoside Analogue Inhibitor - Clinical Therapeutics

Pharmacokinetics and Pharmacodynamics of Setrobuvir, an Orally Administered Hepatitis C Virus Non-Nucleoside Analogue Inhibitor - Clinical Therapeutics | Hepatitis C New Drugs Review | Scoop.it
What do we know about the #pharmacokinetics and #pharmacodynamics of #setrobuvir? http://t.co/ZJgw7NQ9J9 #medcomms #pubplan #HepatitisC

 

Findings

After single doses of setrobuvir (400–3000 mg) to volunteers in a fasted state, peak Cmax and AUC0–∞ increased in a less than dose-proportional manner. The mean apparent t½z ranged from 22.0 to 31.3 hours and was not dose related. Cmax and AUC increased significantly (4.3- and 6.3-fold, respectively) in volunteers who received 2000 mg with a high-fat meal versus fasting. After multiple oral doses, steady state was achieved after 7 days of dosing (400 or 800 mg QD and 600 mg BID) and accumulation was dose-independent. Mean day 14 plasma exposure increased in a less than dose-proportional manner in volunteers who received 400 and 800 mg QD, but it was more than dose-proportional in volunteers receiving 600 mg BID. Dose did not affect the mean t½z (range, 24.1–26.6 hours), apparent oral clearance (0.254–0.516 L/h), or apparent volume of distribution (9.60–18.1 L). In patients with CHC, dose-related reductions in HCV RNA concentration were apparent within 24 hours of the start of treatment. Reductions from baseline to the end of treatment (day 3) in patients treated with setrobuvir 200, 400, and 800 mg BID were –2.1, –2.2, and –2.9 log10 IU/mL, respectively (vs ≤0.1 log10 IU/mL with placebo). Reductions in HCV RNA were greater in patients with genotype 1b (range, –2.7 to –3.1 log10 IU/mL) than in patients with genotype 1a (range, –1.3 to –2.7 log10 IU/mL). Setrobuvir was well tolerated, with no serious adverse events.

Implications

The steady state pharmacokinetics of setrobuvir appear to be dose proportional, and setrobuvir produces a mean reduction of 2.9 log10 IU/mL in HCV RNA over 3 days in patients with genotype 1 (a and b) treated with 800 mg BID. ClinicalTrials.gov identifier: NCT00782353

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The drug is in Phase II trials.

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Treatment of hcv with ABT-450/r–ombitasvir and dasabuvir with ribavirin

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Will AbbVie Undercut Gilead on Hepatitis C? - Barron's (blog)

Will AbbVie Undercut Gilead on Hepatitis C? - Barron's (blog) | Hepatitis C New Drugs Review | Scoop.it
Morgan Stanley’s David Risinger and team downgraded AbbVie (ABBV) to Equal Weight from Overweight today, citing the fact that “risk-reward appears more balanced” now that Street gets the Hepatitis-C and Humira stories.
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A Comprehensive Comparison Of Gilead's Harvoni And AbbVie's Triple HCV ... - Seeking Alpha

A Comprehensive Comparison Of Gilead's Harvoni And AbbVie's Triple HCV ... - Seeking Alpha | Hepatitis C New Drugs Review | Scoop.it
I have been asked by multiple followers to write this piece contrasting Gilead's (NASDAQ:GILD) Harvoni and AbbVie's (NYSE:ABBV) triple regimen which will soon be approved with a PDUFA date of 12/22/2014

 

Gilead's Harvoni will dominate AbbVie's HCV regimen in the market place because in all instances, Harvoni is the safer and more effective drug.Physicians’ primary concern is the well-being of their patients. AbbVie’s regimen requires ritonavir and ribavirin (most cases) which greatly increases side effects and risks of anemia. Harvoni is the best choice.As pricing decreases and regimens improve, more patients will be treated, but the sheer numbers will allow massive profits for at least a decade or more.Gilead shares have dropped 15% over AbbVie's regimen approval and loss of market share due to pricing. The time to buy Gilead is now. Assume 30%-50% upside in 2015.

.

Krishan Maggon 's insight:

Harvoni seems to be safer and more effective than the cheaper AbbVie HCV therapy.

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HCV cirrhosis at the edge of decompensation: Will paritaprevir with ritonavir, ombitasvir, dasabuvir, and ribavirin solve the need for treatment? - Journal of Hepatology

HCV cirrhosis at the edge of decompensation: Will paritaprevir with ritonavir, ombitasvir, dasabuvir, and ribavirin solve the need for treatment? - Journal of Hepatology | Hepatitis C New Drugs Review | Scoop.it
HCV cirrhosis at the edge of decompensation: Will paritaprevir/r, ombitasvir, dasabuvir and R solve the need for tx http://t.co/dVfDKqs8Ji

 

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

METHODS: In this multicenter, randomized, double-blind, placebo-controlled trial, we assigned previously untreated patients with HCV genotype 1 infection, in a 3:1 ratio, to an active regimen consisting of a single-tablet coformulation of ABT-450/r-ombitasvir (at a once-daily dose of 150 mg of ABT-450, 100 mg of ritonavir, and 25 mg of ombitasvir), and dasabuvir (250 mg twice daily) with ribavirin (in doses determined according to body weight) (group A) or matching placebos (group B). The patients received the study treatment during a 12-week double-blind period. The primary end point was sustained virologic response at 12 weeks after the end of treatment. The primary analysis compared the response rate in group A with the response rate (78%) in a historical control group of previously untreated patients without cirrhosis who received telaprevir with peginterferon and ribavirin. Adverse events occurring during the double-blind period were compared between group A and group B.

RESULTS: A total of 631 patients received at least one dose of the study drugs. The rate of sustained virologic response in group A was 96.2% (95% confidence interval, 94.5 to 97.9), which was superior to the historical control rate. Virologic failure during treatment and relapse after treatment occurred in 0.2% and 1.5%, respectively, of the patients in group A. The response rates in group A were 95.3% among patients with HCV genotype 1a infection and 98.0% among those with HCV genotype 1b infection. The rate of discontinuation due to adverse events was 0.6% in each study group. Nausea, pruritus, insomnia, diarrhea, and asthenia occurred in significantly more patients in group A than in group B (P<0.05 for all comparisons). Reductions in the hemoglobin level were all of grade 1 or 2; reductions of grade 1 and 2 occurred in 47.5% and 5.8%, respectively, of the patients in group A, whereas grade 1 reductions occurred in 2.5% of the patients in group B.

CONCLUSIONS: In previously untreated patients with HCV genotype 1 infection and no cirrhosis, a 12-week multitargeted regimen of ABT-450/r-ombitasvir and dasabuvir with ribavirin was highly effective and was associated with a low rate of treatment discontinuation. (Funded by AbbVie; SAPPHIRE-I ClinicalTrials.gov number, NCT01716585.).

Krishan Maggon 's insight:

OA

 

Journal of Hepatology

 

HCV cirrhosis at the edge of decompensation: Will paritaprevir with ritonavir, ombitasvir, dasabuvir, and ribavirin solve the need for treatment?Tarik Asselah, Savino Bruno, Antonio CraxiReceived: June 13, 2014; Received in revised form: August 6, 2014; Accepted: August 9, 2014; Published Online: August 19, 2014 DOI: http://dx.doi.org/10.1016/j.jhep.2014.08.018
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Mayo Clinic on Twitter

Mayo Clinic on Twitter | Hepatitis C New Drugs Review | Scoop.it
Viral liver disease, or Hepatitis C, is the most common reason for liver transplant. #MayoClinicRadio pic.twitter.com/vSVG6f8CNG
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Microbiome: The bacterial tightrope from liver disease to cancer : Nature : Nature Publishing Group

Microbiome: The bacterial tightrope from liver disease to cancer : Nature : Nature Publishing Group | Hepatitis C New Drugs Review | Scoop.it
Imbalances in gut bacteria have been implicated in the progression from liver disease to cancer. This insight opens the way to preventive treatments.
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Krishan Maggon 's curator insight, December 4, 3:59 AM

Liver cancer almost always develops in the wake of preceding problems, such as fatty liver disease (see page S8) or viral hepatitis (see page S12). But it is not clear why some people with such problems go on to develop cancer, whereas others do not — only about 3% of cases become malignant each year. Still, “liver cancer without liver disease is very rare”, says Robert Schwabe, a gastroenterologist and liver researcher at Columbia University in New York. Schwabe, Hara and others think that certain elements in the microbiome might tip the scales towards cancer. If they are right, it could be possible to stop liver disease from turning malignant by targeting microbes in the gut.

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Multivalent N-Acetylgalactosamine-Conjugated siRNA Localizes in Hepatocytes and Elicits Robust RNAi-Mediated Gene Silencing - Journal of the American Chemical Society (ACS Publications)

Multivalent N-Acetylgalactosamine-Conjugated siRNA Localizes in Hepatocytes and Elicits Robust RNAi-Mediated Gene Silencing - Journal of the American Chemical Society (ACS Publications) | Hepatitis C New Drugs Review | Scoop.it

Conjugation of small interfering RNA (siRNA) to an asialoglycoprotein receptor ligand derived from N-acetylgalactosamine (GalNAc) facilitates targeted delivery of the siRNA to hepatocytesin vitro and in vivo. The ligands derived from GalNAc are compatible with solid-phase oligonucleotide synthesis and deprotection conditions, with synthesis yields comparable to those of standard oligonucleotides. Subcutaneous (SC) administration of siRNA–GalNAc conjugates resulted in robust RNAi-mediated gene silencing in liver. Refinement of the siRNA chemistry achieved a 5-fold improvement in efficacy over the parent design in vivo with a median effective dose (ED50) of 1 mg/kg following a single dose. This enabled the SC administration of siRNA–GalNAc conjugates at therapeutically relevant doses and, importantly, at dose volumes of ≤1 mL. Chronic weekly dosing resulted in sustained dose-dependent gene silencing for over 9 months with no adverse effects in rodents. The optimally chemically modified siRNA–GalNAc conjugates are hepatotropic and long-acting and have the potential to treat a wide range of diseases involving liver-expressed genes.

Krishan Maggon 's insight:

J. Am. Chem. Soc., Article ASAPDOI: 10.1021/ja505986aPublication Date (Web): December 1, 2014Copyright © 2014 American Chemical Societyrajeevk@alnylam.com, mmanoharan@alnylam.com

 

GalNAc-siRNA conjugates are a clinically validated, proprietary Alnylam delivery platform and are designed to achieve targeted delivery of RNA therapeutics to hepatocytes through uptake by the asialoglycoprotein receptor (ASGPR). This targeted delivery platform enables specific, potent and durable knockdown of hepatocyte-expressed disease genes with subcutaneous dosing and a wide therapeutic index. GalNAc-conjugates have emerged as a promising strategy for the delivery of RNA therapeutics in advanced pre-clinical and initial clinical studies.

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