Monday, May 16, 2011

Lots Of Monday News:Blockbuster Hepatitis C Cocktails

Hepatitis C drug joins the cocktail party, after a decade of stagnancy
A new hepatitis C drug has come onto the scene — Merck’s boceprevir — after a 10-year lull in HCV therapies entering the market. The FDA’s approval of boceprevir, which will be marketed under the name Victrelis, is a victory for both Merck and HCV patients, as well as for supporters of “cocktail” drug therapies.
What is a therapeutic cocktail, you might ask? There is a growing belief in the medical community that patients with certain viral infections (as well as cancers and other diseases) respond better to a combination of drugs, as opposed to just one drug. Supporting this methodology is a rising trend in drug development in which research trials are increasingly focused on combination treatment regimens, where newer drugs are paired with established therapies.

 Boceprevir approval sets stage for blockbuster hep C cocktails
To almost no one's surprise the FDA announced on Friday that it had stamped Merck's boceprevir--to be sold as Victrelis--with an approval, setting the stage for a more-than-likely approval of telaprevir by the FDA's May 23rd PDUFA date. And the pair of treatments is expected to help usher in a new generation of cocktail therapies for millions of patients threatened by hepatitis C.
The approval for boceprevir came without any of the regulatory strings that some analysts had fretted over. There was no requirement on REMS and no temporary delays as some analysts had predicted. And that open path will encourage other developers advancing their own programs. More hepatitis C drugs are in the pipelines of Roche, Pharmasset and Bristol-Myers Squibb to further advance the standard of care, promising to wipe out the virus earlier with fewer side effects.

Better cure rates
The cure rate of present hepatitis C treatment is around fifty percent. Both boceprevir and telaprevir when combined to the current standard treatment, offer positive results.
Phase 3 clinical trials indicate that boceprevir increased cure rates in both treatment-naïve and treatment-experienced HCV patients to about 66 percent. Cure rates for telaprevir were about 70 to 80 percent for treatment-naïve participants and 65 percent for treatment-experienced patients.
Although the rates for telaprevir seem greater than those for boceprevir, it is not evident whether telaprevir is actually more effective.
The Merck Hepatitis C Med: What The Wags Say
Over at pharmalot columnist Ed Silverman pointed out boceprevirs labeling turned out to be not as restrictive as some forecasted. At the advisory meeting on boceprevir back in April analyst Geoffrey Porges had this to say;
Now that Boceprevir is FDA approved, it seems that a big sigh of relief has been let out by both patients and physicians. Despite this great news and FDA success, the work now starts, evaluating and screening the thousands of patients that have been waiting for this day.
Here is my advice to all concerned patients:
  • I cannot stress the need to get your old records related to past HCV therapies. This will help assist us in how to best manage you on the three-drug combination.
  • Get the report from your most recent liver biopsy. The degree of damage, or lack of it, will be of great value when we discuss how to best treat you.
  • Have an up to date list of all your other medical condition, if this applies to you. Other conditions such as diabetes, heart disease, kidney disease, depression, or cancer will allow us to modify treatment as needed-taylored specifically to you.
  • Have the names and phone numbers of all your treating physicians and health care providers. Communication with them is vital.
This is an exciting time for all of us. Call us if you have questions and concerns. We will be updating the blog and website daily. Stay tuned to these new development.

Telaprevir Improved Outcomes for Hep C Patients Who Failed Prior Therapy
According to final results from the phase III REALIZE trial. Approximately 60% of genotype 1 hepatitis C patients treated with standard therapy do not respond, said Dr. Zobair M. Younossi of Inova Fairfax Hospital in Falls Church, VA. "Re-treating these patients will be very difficult if you want to treat them with the currently available double-combination therapy," said Dr. Younossi, who presented the study findings in a press conference at the annual Digestive Disease Week. The researchers, led by Dr. Paul Pockros of the Scripps Translational Science Institute in La Jolla, Calif., conducted an international, multicenter, double-blind, randomized placebo-controlled trial – the REALIZE trial – to assess the safety and tolerability of adding 750 mg of telaprevir every 8 hours to the standard therapy of 180 mcg/week of pegylated interferon alfa-2a and 1000-1200 mg/day of ribavirin. The control group received the standard therapy plus a placebo.

Scientists have identified two proteins found on the surface of liver cells that help the hepatitis C virus (HCV) enter the cells, the first step in a viral infection that causes liver disease and increases the risk of liver cancer. Both proteins are a type of molecule called receptor tyrosine kinases. Anticancer drugs called tyrosine kinase inhibitors (TKIs) blocked the action of the identified proteins and reduced HCV infection in laboratory models of the disease, reported researchers led by Drs. Joachim Lupberger and Mirjam B. Zeisel from the University of Strasbourg in France. The results were published online April 24 in Nature Medicine.
To identify liver cell proteins that the virus exploits to gain entry, the researchers first used small inhibitory RNAs to block several kinase proteins one by one. They found that silencing the expression of two such proteins—epidermal growth factor receptor (EGFR) and ephrin receptor A2 (EphA2)—stopped HCV particles from entering the cells.

Two approved TKIs, erlotinib and dasatinib, inhibit EGFR and EphA2, respectively. When the researchers treated liver cells with the drugs, HCV entry was impaired. Two other TKIs that inhibit EGFR, gefitinib and lapatinib, had similar effects. In experiments testing cell-to-cell transmission of HCV, erlotinib and dasatinib stopped the virus from spreading from infected cells for up to 2 weeks (the length of the experiment).
Further studies of the cell-signaling networks controlled by EGFR and EphA2 indicated that these proteins do not appear to be necessary for HCV to bind to cells. Instead, they seem to be involved in the virus’ ability to enter the cell. When tested in a mouse model of HCV infection, erlotinib substantially reduced the level of viral infection and was well tolerated.

Chronic hepatitis infection is one of the most common causes of liver cancer, and current treatments are inadequate. Although these findings are preliminary, the authors suggest that targeting receptor tyrosine kinases may provide a new way to prevent HCV infection after exposure and to treat existing HCV infections.
The Victoria Health Department has unveiled that Hepatitis C virus can be transmitted through sexual contacts. The department has diagnosed over the past years 19 out of 37 cases of hepatitis C which are suspected of being sexually transmitted.

It is believed that 37 HIV-positive gay men were infected with hepatitis C and are suspected of transmitting disease to others. It has been told by the Victoria Chief Executive, Helen McNeill that HIV patients suffering from hepatitis C are at higher risk of developing liver disease.

Hepatitis C is a blood-borne virus and can be spread by using infected drug-injections or by blood transfusion. Victoria President, Paul Kidd said that bunch of cases of apparently sexually transmitted hepatitis C between HIV-positive men had been reported overseas including in Britain, France and the Netherlands.
The Health Department is now investigating the cause of the increased number of hepatitis C cases. Prevention is definitely the need of the hour. But the cause of wide spread of hepatitis C is also necessary.
Those who are already affected by the virus are being treated and those in close contact with hepatitis C and are HIV- positive are urged to seek proper medical treatment.
Anemia is associated with virological response in treated HCV/HIV coinfected persons 5/16/2011 News
The latest issue of the Alimentary Pharmacology Therapeutics investigates the incidence, predictors and management of anaemia and its association with virological response in HCV/HIV coinfected persons treated with long-term pegylated interferon alfa 2a and ribavirin.

BioInvent International AB (STO:BINV) and co-development partner ThromboGenics NV (Euronext Brussels: THR) announce today that their partner Roche (SIX: RO, ROG; OTCQX: RHHBY) has dosed the first patient in a phase Ib/II study with the novel antibody anti-cancer agent TB-403 (RG7334). The trial is in patients with glioblastoma multiforme, the most common and aggressive type of primary brain tumour in humans.

The multi-center, phase Ib/II trial will examine the safety and clinical effect of TB-403 in combination with Avastin® (bevacizumab) in patients with recurrent glioblastoma. Secondary objectives include safety, tolerability and pharmacokinetics of the combination. The trial will also include an evaluation of candidate biomarkers. The study will recruit approximately 100 patients.

The start of the phase Ib/II glioblastoma study has triggered a €4 million milestone payment to ThromboGenics and BioInvent. This is the second clinical milestone that they have received from Roche. The first milestone of €10 million was paid last year when Roche initiated an imaging study in patients with colorectal and ovarian cancer.

In March 2011, Roche initiated a phase Ib study of TB-403 in patients with primary liver cancer (hepatocellular carcinoma). This study will determine the safety, tolerability and dosage of TB-403 in combination with Nexavar® (sorafenib), as well as pharmacokinetics and pharmacodynamics. The study will recruit 60-70 patients.

Svein Mathisen, CEO of BioInvent commented, "We are very pleased that Roche has decided to take TB-403 to the next stage of its development. We believe that TB-403 could make a major contribution to the armamentarium used to treat cancer. In glioblastoma, the medical need is significant and it is our hope that this unique product candidate could improve the prospects for this patient group whose current treatment options are very limited."

Dr Patrik De Haes, CEO of ThromboGenics, added, "The start of these trials reflects a great interest in evaluating TB-403, in combination with more established oncology drugs, in a range of cancer indications. The glioblastoma study, using TB-403 together with Avastin, is designed to find better treatment options for patients with this very aggressive form of brain cancer. I believe that these studies will confirm that the further development of this novel selective anti-angiogenic antibody is warranted."


About TB-403

The novel mechanism of action of TB-403 represents a potentially promising cancer therapy. It is a humanized monoclonal antibody directed towards placental growth factor (PIGF), expected to act by blocking the formation of the new blood vessels that are required for tumour growth. Preclinical exploration of PIGF biology suggests a role in tumour angiogenesis and metastasis and a limited role in the maintenance of normal vasculature. This mode of action could result in therapeutic benefit with an acceptable side effect profile.

Two phase I clinical trials have found that TB-403 was well tolerated with no reported dose limiting toxicity.

BioInvent International AB
Ligand Pharmaceuticals Inc. said Thursday it licensed two liver disease drugs to drugmaker Chiva Pharmaceuticals Inc. as part of a deal that could be worth more than $100 million.

The deal gives Chiva the rights to develop and market the drugs in China. The partnership includes Pradefovir, a potential treatment for hepatitis B, and MB01733, which is being tested as a treatment for hepatocellular carcinoma, the most common type of liver cancer. Ligand said Chiva is also getting a non-exclusive license for newer drugs that could be used to treat hepatitis B and C and hepatocellular carcinoma.
Chiva is headquartered in Los Altos Hills, Calif., but Ligand said it is an affiliate of Hainan Kaihua Pharmaceutical Co., a drugmaker that focuses on the Chinese market.

The San Diego drugmaker said it could get more than $100 million in milestone payments and royalties on sales if the products are approved. It could receive up to $1 million in license payments in 2011. Ligand said it could also get a 10 percent equity stake in Chiva. If Chiva licenses the drugs to another company, Ligand will get a portion of that revenue.
Ligand acquired the drugs in January 2010 when it bought Metabasis Therapeutics Inc.

After testing 4312 of James Latham Peters' patients between 2006 and 2009, 49 women who had procedures at the Croydon Day Surgery have been confirmed as having the same strain of the disease as the anaesthetist.

All of the patients had procedures at the clinic from January 2008 to December 2009.
None of Dr Peters' patients at the Fertility Control Clinic in East Melbourne, St Albans Endoscopy Centre or the Western Day Surgery tested positive to hepatitis C that could be linked to him.
Dr Peters is currently under police investigation and had his registration suspended by the Medical Practitioners Board of Victoria in February 2010.
Victoria's Chief Health Officer John Carnie the 49 patients were definitely linked to Dr Peters.
'This is an extremely traumatic and distressing episode for these patients,' he told reporters in Melbourne on Monday.

'Many of them will be extremely angry that they have been put at risk.
'I would find it very difficult to determine some accidental means (of transmission) that would involve this number of patients at just the one clinic.'

by Kate Bruce-Rosser
THE Health Department has wound up its investigation into a cluster of hepatitis C cases linked to a Croydon abortion clinic.

Victoria’s Chief Health Officer, Dr John Carnie, this afternoon confirmed that 49 women had the same strain of the virus as the clinic’s former anaesthetist, Dr James Latham Peters.
“All of these women had procedures at the Croydon clinic between January 2008 and December 2009,’’ Dr Carnie said.
“In a further 19 cases, initial testing indicated past infection with hepatitis C but the patients had either cleared the virus from their blood or there was insufficient virus present to make a definitive ruling.’‘
‘In addition there were 241 patients we have been unable to contact, despite repeated calls and registered letters.

“And there were another 247 cases where results have not been provided to the department.’‘
More than 4000 patients - including 3000 from the Croydon clinic - were contacted and tested during the department’s investigation.

Dr Carnie said, as an added precaution, the investigation was extended to more than 1000 patients who underwent procedures involving the anaesthetist at three other facilities between 2008 and 2009: the Fertility Control Clinic, St Albans Endoscopy Centre and the Western Day Surgery.
“There were no cases of hepatitis C which could be linked to the anaesthetist at any of these facilities,’’ he said.

“It is important to stress there has not been any hepatitis C risk to anyone undergoing surgery at any of these facilities.’‘

“All patients had access to free testing and counselling. All women found to be positive were referred promptly for expert assessment and treatment.”

Dr Carnie said any concerned patient could contact the Communicable Disease Prevention and Control Unit on 1300 651 160.
General information about hepatitis C is available on the Better Health Channel at

Complementary Medicine / Alternative Medicine
The Science Unit's Joel Werner takes a look at how complementary medicines are regulated

A bioethics expert from the University of Abertay Dundee has denounced the public funding of homeopathy at a time where Scotland's health budget is under unprecedented pressure. Speaking in the esteemed journal 'Bioethics', Dr Kevin Smith says that Homeopathy is 'ethically unacceptable' and should be 'actively rejected' by healthcare and education providers.
Colloidal Silver -FDA Issues A Warning Letter
Colloidal silver is peddled as a treatment for hepatitis C, if not a cure, according to the recent April 11th FDA warning letter  sent to International Institute of Holistic Healing, Inc., Colloidal silver is recommended and sold online for treating AIDS, Cold Sores, Liver Disease, Genital Herpes, Genital Warts, and HIV.

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1 comment:

  1. Re: Hepatitis C: A Sexually Transmitted Disease

    The state of Victoria in SE Australia does not have a chief executive or a president and neither does Australia. Helen McNeill is Chief Executive of Hepatitis C Victoria who represent and advocate for people with Hep C. Paul Kidd is president of the board of People Living with HIV/AIDS Victoria who represent and advocate for people living with HIV. These are crucial factors basic to journalism but completely warped here.

    Further, the infections were diagnosed this year, not "over the past years" - which have been previously document in other research that included Sydney (not in Victoria), ie Victoria has not just "unveiled that Hepatitis C virus can be transmitted through sexual contacts". We have been talking about it for at least 5 years - eg, see GV Matthews et al 2007 AIDS 21:2112.

    Also I do not believe the Health Department has said that the 19 or the 37 "are suspected of transmitting disease to others" But that the 19 share the same strain forming a genotype cluster suggesting they may have infected each other - which is a very different thing.

    This is the worst piece of journalism I have seen for a long time and just when people need to be informed properly.
    Eric Glare, speaker and advocate, Positive Speakers Bureau, People Living with HIV/AIDS Victoria.