Can Indian generic makers find gold with a blockbuster Hepatitis C drug?

For patients with Hepatitis C, Dr Parveen Malhotra prescribes a tablet that doctors say is revolutionising the treatment paradigm for the dreaded liver ailment. The hepatologist from Haryana's Rohtak town too has reported a higher cure rate since switching to the orally administered sofosbuvir from the injectable interferon five months ago.

According to World Health Organization data, hepatitis C kills half a million people a year and infects 150 million globally. Screening often includes costly multiple tests without which the ailment often goes undetected. In this backdrop, say doctors, sofosbuvir, is proving to be a magic bullet, unlike some of the alternatives that came with a host of side effects.

"This molecule (sofosbuvir) is revolutionary. Earlier we used to treat with interferon therapy, but here you have for the first time a therapy in oral form. With this molecule the ease of treatment has improved," said Dr Mandar Kubal, director of Mumbai based Infectious Diseases & Pulmonary Care.

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Canada: Psychosis, Hepatitis C linked to high death rate in Downtown Eastside: UBC

The mortality rate in the Downtown Eastside is eight times the national average, according to a new UBC study that followed 371 people for about four years. 

 

The death rate in the Downtown Eastside is eight times higher than the Canadian average, and treatable problems are linked to mortality, according to research from the University of British Columbia published last month.

Psychosis and liver problems related to hepatitis C were the highest risk factors for mortality, according to the study of 371 people over about four years.

Researchers recruited the participants from single-room occupancy hotels and the Downtown Community Court. Thirty-one of them died.

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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 Pérez-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

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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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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