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Alan Franciscus

Editor-in-Chief

HCV Advocate



Thursday, September 10, 2015

Modeling the helicase to understand hepatitis C

NS3 behaves like a 'caterpillar' and helps the virus to replicate

NS3 is an enzyme specific to the hepatitis C virus. If developed, a drug capable of recognizing and selectively attacking it could fight the disease without side effects for the body. However, to be able to develop one we need to know more about the behavior of this important protein in the virus replication process. Some SISSA scientists have provided a detailed and comprehensive view of the behavior of NS3. The study has been published in the journal Nucleic Acids Research.

According to the WHO, a good 140 million people are affected by hepatitis C (3/4 million new cases per year). This is still a subtle disease which, in the event of chronic infection, heavily affects the patients' quality of life and whose complications can lead to death. One of the molecules involved in the reproduction mechanism of the virus in the body is a helicase, NS3, an enzyme that interacts with the RNA (the viral genome, which is not like our DNA) by climbing onto it and helping the pathogen's replication process.

"By knowing in detail how this helicase works, in the future we could try to block the viral replication, and thus stop the disease from proliferating in the body" explains Giovanni Bussi, SISSA professor and among the study authors. NS3 facilitates the work of the polymerases, the molecules that build a replica of the RNA strand, by "opening" and preparing the RNA to the action of the second enzyme. "NS3 crawls along the RNA strand contracting and extending like a caterpillar and, as it does so, it releases the part of the virus to which the polymerase then attaches" explains Andrea PĂ©rez-Villa, SISSA student and first author of the paper. "We decided to analyze this protein because, unlike others, it is only present in the hepatitis C virus. This way, any drug capable of targeting its interaction with the RNA would not damage other proteins, for example, those belonging to the body being attacked by the virus. This means that, theoretically, the drug would have no side effects".


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FDA Issues Pediatric Warning for Copegus


Copegus (ribavirin) tablets

Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)

August 2015

WARNINGS AND PRECAUTIONS

Impact on Growth in Pediatric Patients
  • During combination therapy for up to 48 weeks with PEGASYS plus ribavirin, growth inhibition was observed in pediatric subjects 5 to 17 years of age. Decreases in weight for age z-score and height for age z-score up to 48 weeks of therapy compared with baseline were observed. At 2 years post-treatment, 16% of pediatric subjects were more than 15 percentiles below their baseline weight curve and 11% were more than 15 percentiles below their baseline height curve. The available longer term data on subjects who were followed up to 6 years post-treatment are too limited to determine the risk of reduced adult height in some patients


ADVERSE REACTIONS

Growth Inhibition in Pediatric Subjects
  • Pediatric subjects treated with PEGASYS plus ribavirin combination therapy showed a delay in weight and height increases with up to 48 weeks of therapy compared with baseline. Both weight for age and height for age z-scores as well as the percentiles of the normative population for subject weight and height decreased during treatment. At the end of 2 years follow-up after treatment, most subjects had returned to baseline normative curve percentiles for weight (64th mean percentile at baseline, 60th mean percentile at 2 years post-treatment) and height (54th mean percentile at baseline, 56th mean percentile at 2 years post-treatment). At the end of treatment, 43% (23 of 53) of subjects experienced a weight percentile decrease of more than 15 percentiles, and 25% (13 of 53) experienced a height percentile decrease of more than 15 percentiles on the normative growth curves. At 2 years post-treatment, 16% (6 of 38) of subjects were more than 15 percentiles below their baseline weight curve and 11% (4 of 38) were more than 15 percentiles below their baseline height curve. Thirty-eight of the 114 subjects enrolled in the long-term follow-up study, extending up to 6 years posttreatment. For most subjects, post-treatment recovery in growth at 2 years post-treatment was maintained to 6 years post-treatment.
Source:  http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm218877.htm

Wednesday, September 9, 2015

Sovaldi-Based Hep C Regimens Less Successful in Real World

The real-world cure rates offered by Sovaldi (sofosbuvir)–based hepatitis C virus (HCV) regimens have not been as good as those seen in clinical trials, at least among a group of veterans with genotypes 1 or 2, Healio reports. Publishing their findings in Alimentary Pharmacology & Therapeutics, researchers analyzed data from the Veterans Affairs Clinical Case Registry for HCV on 4,026 vets treated for hep C with 12-week Sovaldi–based regimens.

A total of 3,203 of the vets had genotype 1 and 823 had genotype 2.

Gilead Sciences’ Harvoni (ledipasvir/sofosbuvir) has superseded Sovaldi–based regimens (Sovaldi is also a Gilead drug) as the treatment of choice for those with genotype 1. So this study’s findings may not be applicable to the current realities of hep C treatment among that group, especially since this study looked in part at the results of regimens including interferon, which causes flu-like side effects. Interferon has largely been edged out of the hep C arsenal.

However, 12 weeks of Sovaldi plus ribavirin is still the top-recommended regimen for treatment-naive people with genotype 2, which makes  this study more relevant to that population’s current concerns.

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Tuesday, September 8, 2015

Iran: Hepatitis C drug to be released

TEHRAN, Sep. 08 (MNA) – Deputy health minister has reported on the entry of home-made Hepatitis C drug to the country’s pharmaceutical market next week noting that it has been produced by Iranian knowledge-based companies.

“The Sofosbuvir drug is used to treat hepatitis C cases; previously it was imported from other countries and priced at $100 per tablet but the indigenous version will be available at the price of 10 dollars per tablet,” said Reza Malekzadeh at a press conference on knowledge-based companies reminding that, “in terms of quality, this drug fully complies with foreign ones and there is no difference in terms of efficiency or treatment of the disease.”

He also reported the production of two other combination drugs to treat hepatitis C in the country adding that they are currently at laboratory stage and will soon be released. “There are now drugs that can treat hepatitis C and there exists the possibility of eradication of the hepatitis C virus in the country in near future; hepatitis C has a three-month course of treatment and patients should take one tablet per day for full treatment,” added Malekzadeh.

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Medicines Patent Pool looks at hepatitis C

Greg Perry, Executive Director of the Medicines Patent Pool, told delegates at the World Hepatitis Summit in Glasgow this week that the organisation was considering how it could act to speed up and expand access to direct-acting antivirals for lower- and middle-income countries, where around 85% of people with hepatitis C are estimated to live.

The Medicines Patent Pool was established with the support of UNITAID, the international drug and diagnostics purchase fund for HIV, tuberculosis and malaria, to negotiate voluntary licensing agreements with pharmaceutical companies that would allow widespread access to low-cost antiretroviral drugs for HIV treatment. The Medicines Patent Pool was also designed as a mechanism to overcome barriers to the development of fixed-dose drug combinations of products from more than one manufacturer, for efficient delivery of treatment in lower- and middle-income countries.

Since its launch in 2010 the Medicines Patent Pool has negotiated voluntary licensing agreements with all the major pharmaceutical companies that allow some or all of their antiretroviral products to be copied by generic manufacturers for sale at greatly reduced prices in lower- and middle-income countries.

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Study’s Findings Could Help Expand the Donor Pool for Liver Transplantation

Organ donation after circulatory death (DCD), in which transplant organs are taken from donors after ay period of no blood circulation or oxygenation, is often considered inferior to donation after brain death, in which circulation and oxygenation are maintained until organs are removed for transplantation. Currently, the use of livers from DCD donors remains controversial, particularly with donors with advanced age.

A new study of DCD liver transplantations conducted at the Cleveland Clinic from 2005 to 2014 found no significant correlation between donor age and organ survival, however. The results suggest that stringent donor and recipient selection may ameliorate the negative impact of donor age in DCD liver transplantation.

“Aged DCD organs are generally underutilized by many transplant surgeons because of the higher risk of transplant organ failure; however, by eliminating other risk factors, aged DCD organs can greatly help expand the donor pool for life-saving liver transplantation,” said Dr. Koji Hashimoto, co-author of the Liver Transplantation study.

Source:  http://ca.wiley.com/WileyCDA/PressRelease/pressReleaseId-120486.html

Monday, September 7, 2015

What’s behind Hepatitis C increase in Franklin County?

GREENFIELD — As Hepatitis C rates have risen sharply in Franklin County, neighboring Hampshire County has seen a slower trend and a lower rate, tempered perhaps by prevention efforts.

Franklin County’s rate of 131 newly discovered Hepatitis C cases per 100,000 residents in 2014 was just under the statewide rate of 134, while Hampshire County trailed with a rate of 73. This is a population-adjusted measure, using numbers collected by the Mass. Department of Public Health. In simple numbers, Franklin County had 94 new cases in 2014 and Hampshire County 116.

Greenfield saw 40 newly discovered cases of the blood-borne liver disease in 2014, while its larger sister to the south saw 29. Northampton’s population of 28,549 at the last census outnumbered Greenfield 3 to 2.

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