HCV New Drugs: Hang On-Hepatitis C News: Boceprevir,Telaprevir, and ACH-1625

HCV Protease Inhibitor Boceprevir Improves Response for Treatment-Naive and Non-responders
SUMMARY: Merck's investigational hepatitis C virus (HCV) protease inhibitor boceprevir improved sustained response rates when combined with pegylated interferon plus ribavirin in both previously untreated patients and those who were non-responders or relapsers after prior therapy, according to 2 Phase 3 studies presented at the 18th Conference on Retroviruses and Opportunistic Infections (CROI 2011) this month in Boston...Continue reading...

CROI:
The Effect of Low-dose Ritonavir on the Pharmacokinetics of the Investigational HCV Protease Inhibitor Telaprevir in Healthy Volunteers -

Little Overlap of Sexually Transmitted HCV between U.S. and Europe
SUMMARY: A phylogenetic analysis of more 200 hepatitis C virus (HCV) strains from HIV positive gay and bisexual men revealed extensive clustering of related viruses within U.S. cities, but little overlap between the East and West coasts, or between the U.S. and Europe or Australia, according to findings presented at the at the 18th Conference on Retroviruses and Opportunistic Infection (CROI 2011) this month in Boston...Continue reading..

Information;FDA Advisory Committee Meeting On Boceprevir and Telaprevir
The Food and Drug Administration will convene its Antiviral Drugs Advisory Committee on April 27 and 28, 2011 to provide advice and recommendations to the Agency on two drugs intended to treat hepatitis C.On April 27, 2011, from 8 a.m. to 5 p.m., the Committee will discuss a new drug application (NDA) 202–258, boceprevir (a hepatitis C virus protease inhibitor), manufactured by Merck & Co., Inc., with a proposed indication for the treatment of chronic hepatitis C genotype 1 infection, in combination with peginterferon alfa and ribavirin (two medicines approved to treat chronic hepatitis C infection) in adult patients with compensated liver disease who are previously untreated or who have failed previous therapy.

n April 28, 2011, the committee will discuss a new drug application (NDA) 201–917, telaprevir (a hepatitis C virus protease inhibitor), manufactured by Vertex Pharmaceuticals, Inc., with a proposed indication for the treatment of chronic hepatitis C genotype 1 infection, in combination with peginterferon alfa and ribavirin (two medicines approved to treat chronic hepatitis C infection) in adult patients with compensated liver disease who are previously untreated or who have failed previous therapy.Compensated liver disease is a stage in which the liver is damaged but maintains ability to function..........continue reading..

March 16, 2011

Telaprevir, Boceprevir for Hep C Approaching FDA Finish Line

Two experimental hepatitis C virus protease inhibitors are scheduled to undergo approval review by the U.S. Food and Drug Administration’s Antiviral Drugs Advisory Committee at the end of April, according to a report from Dow Jones Newswires.

Approval applications for Merck’s boceprevir will be reviewed by the committee April 27, whereas documentation supporting Vertex’s telaprevir will be reviewed April 28. Upon completing its review of each new drug application (NDA) and hearing from researchers, hepatitis C community advocates and the drugs’ sponsors, the committee will recommend to the FDA whether or not to approve the drugs.

Both drugs are expected to come to the market at similar times and to be widely used, according to the Dow Jones report. The report adds that Merck was granted an expedited six-month review by the FDA in 2011; Vertex is expecting an approval decision by May 23.

According to clinical trial data reported by researchers thus far, both drugs substantially increase the likelihood of sustained virologic responses (SVRs)—defined as HCV viral loads that remain undetectable after treatment is discontinued—in both patients starting hepatitis treatment for the first time and those who did not respond favorably to treatment in the past.

Both telaprevir and boceprevir must be combined with pegylated interferon and ribavirin for the first three months of treatment.
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Nonsurgical Hepatic Decompression In Budd-Chiari
16 March 2011Budd-Chiari syndrome (BCS) results from hepatic venous outflow obstruction at any level from hepatic venules to the right atrium. Few patients respond to medical treatment (anticoagulation with or without thrombolytic therapy, diuretics)...Continue reading

HBV
Hepatitis B Vaccination Dramatically Lowers Prevalence among U.S. Children
SUMMARY: Children and adolescents in the U.S. today have a very low likelihood of hepatitis B virus (HBV) infection thanks to widespread vaccination, according to an epidemiological study described in the March 1, 2011, Annals of Internal Medicine. Many adults remain vulnerable, however, underlining the importance of vaccination for at-risk groups.

HIV
18th Conference on Retroviruses and OpportunisticInfections (CROI 2011)
February 27 - March 2, 2011, Boston, MA

Healthy You
Cirrhosis:Importance Of Monitoring Vitamin D
The Importance Of Monitoring Vitamin D Levels In All Patients With Cirrhosis
Vitamin D deficiency is a well reported complication in chronic cholestatic liver disease such as primary biliary cirrhosis. While the prevalence and treatment of this deficiency has been addressed in many articles over the last decades, little is known of the vitamin D status in alcoholic liver cirrhosis.......Continue reading..

Perilous Infection Control Practices with Needles, Syringes, and Vials Suggest Stepped-up Monitoring is Needed
Posted: 03/14/2011; ISMP Medication Safety Alert © 3011
Institute for Safe Medication Practices

Posted: 03/14/2011; ISMP Medication Safety Alert © 3011 Institute for Safe Medication PracticesA recent online survey of 5,446 healthcare practitioners reveals an alarming lapse in basic infection control practices associated with the use of syringes, needles, multiple-dose vials, single-use vials, and flush solutions.[1] Survey respondents primarily included registered nurses (89.5%) who worked in hospitals. While the majority of nurses and other healthcare practitioners appear to follow infection control practices consistent with current recommendations,[2] some survey respondents clearly place patients at risk for transmission of blood-borne diseases, according to information we received from the survey sponsor, Premier Healthcare Alliance, while highlighting publication of the survey by Pugliese et al. in the American Journal of Infection Control (www.premierinc.com/injectionpractices).[1]

Pharmaceuticals
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Achillion Pharmaceuticals receives key US patent for Hep C drug

10:07 am

by Deborah Sterescu

Drug developer Achillion Pharmaceuticals (NASDAQ:ACHN) said Wednesday that it has received a US patent for ACH-1625, an investigational drug designed to treat the hepatitis C virus. The new patent, which covers composition of matter and method of use, has a term until 2029, the company said. "This key patent grant provides a cornerstone for Achillion's intellectual property portfolio for ACH-1625 and a number of structurally related compounds," said president and CEO Michael D. Kishbauch. The company is expecting phase 2 clinical trial results for ACH-1625 in the next months, and is also planning to move two other compounds into phase 1 trials during the first half of the year.

A wild ride in Hepatitis C treatment
A wild ride in Hepatitis C treatment: Vertex stock gives investors whiplash

March 14th, 2011 5:56 pm ET

Elisabeth Morris Boston Health News Examiner

Has anyone noticed that Vertex Pharmaceuticals, Cambridge MA (VRTX, Nasdaq) stock has been bouncing around like a ping pong ball during the last months? Traders have been consistently excited about the positive news from Vertex’s Hepatitis C virus (HCV) treatment telaprevir. And some news about a treatment for cystic fibrosis pushed the stock to it’s 52 week high on March 4. But investors reacted (or should we say over-reacted) quite strikingly to some extremely early, positive (but as yet unpublished) results from a very short and small study testing efficacy of Pharmaset’s Hepatitis C treatment, and Vertex’s stock lost 12% of it’s value abruptly last week. Now Vertex stock is undergoing a small uptick based on positive results from it’s anti-inflammatory to treat epilepsy. What a roller coaster ride! It is really very unlikely that any of these results justify such large changes in the value of the company’s stock.

Let’s go back to telaprevir, the treatment for Hepatitis C that is the foundation of Vertex’s value at this point. Hepatitis C virus is a leading cause of chronic liver disease in the United States, and it is estimated that 170 million people worldwide have clinical signs from Hepatitis C virus infection. HCV can cause acute liver disease with severe symptoms, but about 75% of patients develop chronic HCV which can vary from asymptomatic to chronic liver failure and cirrhosis over a course of 10-20 years. HCV is a enveloped, single stranded RNA virus which infects liver cells, proliferates in the cell and then goes on to infect many more cells with each replication process. The end result is destruction of the liver. The viral replication process requires the virus to make an enzyme called NS3/4A. When telaprevir is in the circulation, it binds to the NS3/4A enzyme and prevents the virus from proliferating in the liver cell. ...Continue reading..

Mar 15, 2011 07:42AM
FDA: Overseas manufacturing puts U.S. at risk
So many of the drugs approved in the U.S. are manufactured overseas that the FDA is having a hard time keeping up with inspections in the supply chain. The result could be another tainted-drug disaster just waiting to happen. This is not an FDA watchdog with an agenda sounding the alarm; the agency itself came out with the dire warning.

"The safety of America's food and medical products is under serious challenge," warned senior FDA official John Taylor, who was speaking at a Pew Health Group meeting. He raised the specter of "another public health crisis like Heparin." In 2008, contaminants in the blood thinner Heparin produced in China led to more than 100 deaths in the U.S.

Pharmalot's Ed Silverman puts the problem in perspective. The number of foreign manufacturing plants grew to more than 3,500 in 2008--up from roughly 1,200 in 2001, he writes. That's a 185 percent increase. Yet the number of FDA inspections rose 23 percent, leading to a 57 percent drop in the inspection rate.
Some of the solutions the FDA has mentioned include more partnering with foreign counterparts and hiring of private inspectors.
- read Silverman's report on Pharmalot- and another report on CNNMoney
Related Articles:FDA to contract out more foreign inspections FDA needs to refocus plant inspections, GAO says Dems float bill to boost FDA's foreign powers

Mar 15, 2011 08:02AM
Portrait of an Indian Pharma acquisition 'failure'
The Wall Street Journal features a little case study in what can go wrong three years after an acquisition that was once billed as a match made in pharmaceutical heaven.
Back in June 2008, Tokyo-based Daiichi Sankyo acquired India's Ranbaxy, a drugmaker specializing in generics, for $4.6 billion. At the time, Daiichi said the acquisition would help it access the American and Indian markets.
Ranbaxy CEO Malvinder Singh had vowed that the company "was in his genes" and would not jump ship. Fast-forward about a year, and Singh parachuted out, clutching a 4.5 billion rupee severance package, according to the WSJ.
What went wrong? Timing. Three weeks later, the FDA banned imports of 30 of Ranbaxy's generic drugs. What went right? After some initial stumbles, Daiichi has indeed gained some synergies with Ranbaxy's R&D. But the overall verdict from the WSJ is "fail."
"This is a classic example of an acquirer paying top price without looking too closely at the quality of the goods," the analysis concludes.
- read the whole thing in WSJ's Deals India

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Of Interest

Concerns Grow Over Medical Tourism in Asia

One of the fastest growing businesses around the world, particularly in Asia, is medical Tourism.

How fast is medical tourism growing? Dr David Vequist, who heads the Center for Medical Tourism Research in San Antonio, Texas says one medical research organization predicts explosive growth.

“According to Fox and Sullivan, by 2012, it’s expected to be worldwide about a $100-billion business, and it’s growing worldwide from 20 to 30 percent. There was a recent estimate that in Asia alone, it was growing as much as 17 percent," he said.

And Vequist says many of the medical facilities around the world are giving the best medical facilities in the United States a run for their money.

“The Johns Hopkins, the Mayo Clinic, the Texas Medical Center, MD Anderson, Cedar Sinai, these really great facilities in the United States that arguably are among the best in the world are receiving more and more competition from best in class facilities in places like Turkey at Parkway Hospital or Bumrungrad in Thailand or Severance in Korea. These locations around the world are getting very good," he said.

But then there is the down side. Glen Cohen, Co-Director of the Petrie-Flom Center for Health Law Policy, Biotechnology and Bioethics at the Harvard Law School says there is evidence that profitable medical tourism is taking away medical services from the poor in some host countries

“In India, for example, there have been a number of anecdotal claims that the existence of the medical tourism industry has siphoned doctors away from treating poor Indian patients and has basically resulted in a net loss for India’s poor. There are others who say no, it’s quite the opposite, that there is an infusion of technology, there is trickledown economics. Again, it’s a contested empirical claim. But beyond that, there is an ethical claim about whether you’ve done something wrong," he said.

Much of China’s medical tourism industry has focused on organ transplants, reportedly about 10,000 of them a year, mostly kidney and organ transplants. The Chinese government has admitted that some of the organs for transplantation have come from executed prisoners.

Nancy Scheper-Hughes, a professor of medical anthropology at the University of California at Berkley and a co-founder and director of the medical rights organization Organs Watch says many of those have lead to very bad results.

“I am in touch [with] a number of families who have had disastrous transplants in China because it was so unregulated. A family named the McGalkers, in Israel, they were of Indian background, went to China in 2009. It was just a horror show. The father had a botched transplant with a 15 year old village girl. Mr. McGalker died and as a result had to be air shipped out, the young donor died. This is serious business. Not just using executed prisoners but setting up living liver transplants and no regulation," she said.

That has recently changed as China has enacted new regulations surrounding transplants. One proposed law would give the death penalty to anyone found guilty of illegal organ trafficking. However Scheper-Hughes says the entire process brings up troubling consequences.

“It does turn doctors and ministries of health into brokers because you still have to find people and it’s not going to be your children or my children. It’s going to be ethnic minorities, the poor, the desperate, the imprisoned people, the people who are looking for visas, the displaced populations of the world, the refugees," she said.

China is also moving forward on plans to set up and market treatment using stem cell therapy that, for the most part, is unavailable in the United States.

Professor Glenn Cohen of the Harvard law school said, “Many scientists think in the next 50 years or so, many of the breakthroughs in medicine may be related to stem cell therapies. So obviously this is promising and obviously with terminally ill patients who have exhausted all approved therapies or clinical therapies in the U.S., the calculus is quite different in terms of the safety and efficacy. But there are significant risks when you engage in any experimental therapy and stem cells are no different. And I’m not really aware of too many success stories in this regard.”

If you are considering availing yourself of the ever growing medical tourism offerings, Cohen said in addition to ethical concerns, there are at least three concerns that must be addressed.

“One is the quality of service that’s being provided to you abroad. The second concern is that if something does go wrong, what is your ability to recover a medical malpractice by suing the doctors abroad, and the third maybe is the willingness to get a doctor in your home country to engage in follow up care, the availability of health records and what the quality of care will be back home," he said.

Even with all of these concerns, medical tourism continues to expand. Reasons why and some services that are likely to become available, are the subject of the next report.
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Related On The Blog;
'60 percent of liver transplants done in China not successful’
Organ Harvesting In China
Reality Check: The Outsourcing Of Clinical Trials/Drugs
Hepatitis C News; Organs For Sale
Six Kosovar doctors face charges of illegal organ trafficking.

Journal Citations

Hepatitis C virus infection during pregnancy and the newborn period - are thereopportunities for treatment?

Arshad M, El-Kamary SS, Jhaveri R.J Viral Hepat. 2011 Apr;18(4):229-36.

Quartuccio L, Maset M, Di Loreto C, De Vita S.Clin Exp Rheumatol. 2011 Feb 2. .

Survival rates of early-stage HCV-related liver cirrhosis patients without hepatocellular carcinoma are decreased by alcohol.

Yamada M, Shiroeda H, Hayashi R, et alJ Clin Biochem Nutr. 2011 Mar;48(2):167-9.

Hepatic steatosis and insulin resistance are associated with severe fibrosis in patients with chronic hepatitis caused by HBV or HCV infection.

Petta S, Cammà C, Marco VD, et alLiver Int. 2011 Apr;31(4):507-15

Risk of kidney cancer and chronic kidney disease in relation to hepatitis C virus infection: a nationwide register-based cohort study in Sweden.

Hofmann JN, Törner A, Chow WH, et alEur J Cancer Prev. 2011 Mar 6.

Outcomes for adult living donor liver transplantation: Comparison of A2ALL and national experience.

Olthoff KM, Abecassis MM, Emond JC, et alLiver Transpl. 2011 Feb 25.

Adherence to treatment and quality of life during hepatitis C therapy: a prospective, real-life, observational study.