CDC makes recommendation for HCV testing...

Posted 8/16/2012 on the CDC website. This new CDC recommendation that all of those born between 1945 and 1965 get tested for Hepatitis C is critical for HCV drug developers in that it will drive patients for the 2nd and 3rd wave of therapies currently in development. The recommendation is as important as the recommendation for colon cancer screening and, with proper mainstream media leverage, has the potential to drive patients into physician offices in similar volume. The upside is a potential second surge with current therapy and certainly immense anticipation for the simpler, more tolerable pan-genotypic 2nd and 3rd waves of HCV therapy currently in development. The potential downside is that the sheer number of patients may be the tipping point for an already overloaded and politically charged health care system short on resources.

CDC Now Recommends All Baby Boomers Receive One-Time Hepatitis C Test

New approach will help avert major increases in liver disease and deaths in the U.S.

All U.S. baby boomers should get a one-time test for the hepatitis C virus, according to final recommendations published today by the Centers for Disease Control and Prevention. One in 30 baby boomers – the generation born from 1945 through 1965 – has been infected with hepatitis C, and most don’t know it. Hepatitis C causes serious liver diseases, including liver cancer (the fastest-rising cause of cancer-related deaths) and is the leading cause of liver transplants in the United States.

The final recommendations are published in today’s issue of CDC’s Morbidity and Mortality Weekly Report. Draft recommendations were issued in May, followed by a public comment period.

“A one-time blood test for hepatitis C should be on every baby boomer’s medical checklist,” said CDC Director Thomas R. Frieden, M.D., M.P.H. “The new recommendations can protect the health of an entire generation of Americans and save thousands of lives.”

CDC’s previous recommendations called for testing only individuals with certain known risk factors for hepatitis C infection. Risk-based screening will continue to be important, but is not sufficient alone. More than 2 million U.S. baby boomers are infected with hepatitis C – accounting for more than 75 percent of all American adults living with the virus. Studies show that many baby boomers were infected with the virus decades ago, do not perceive themselves to be at risk, and have never been screened.

More than 15,000 Americans, most of them baby boomers, die each year from hepatitis C-related illness, such as cirrhosis and liver cancer, and deaths have been increasing steadily for over a decade and are projected to grow significantly in coming years.

CDC estimates one-time hepatitis C testing of baby boomers could identify more than 800,000 additional people with hepatitis C. And with newly available therapies that can cure up to 75 percent of infections, expanded testing – along with linkage to appropriate care and treatment – would prevent the costly consequences of liver cancer and other chronic liver diseases and save more than 120,000 lives.

Comments received from individuals and organizations during the public comment period (May 22-June 8, 2012) overwhelmingly supported CDC’s original proposal. As a result, the agency did not make substantive changes to the draft recommendations.

For additional information about hepatitis, visit www.cdc.gov/hepatitis.

Seeking Alpha: Is The Hep C Drug Pipeline Beginning To Crack?

Posted on 8/19/12 on Seeking Alpha.com. Commentary by Tiran Rothman from Bioassociate Consulting on the current state of affairs in HCV drug development. His feeling is that the troubles with the NS5A inhibitors may give formerly dark horse companies developing drugs with differing approaches to tackle the virus (mentioned are BioLineRx with it's BL-8020 entry inhibitor and Transgene's TG4040 therapeutic vaccine) a chance to shine. 

Is The Hep C Drug Pipeline Beginning To Crack?

By Tiran Rothman

Another crack appeared today in the ultra-hype of next generation Hep C drugs. Idenix Pharmaceuticals (IDIX) released news that its Phase IIb trial with IDX184 was put on partial clinical hold by the FDA due to the recent cardiovascular toxicity experienced by a patient treated with a similar treatment developed by Bristol-Myers Squibb (BMY). Idenix's investors were quick to pull the trigger, sending the stock for a 40% nosedive.

Both Idenix's IDX184 and BMS's 094 are NS5 family inhibitors, which are the front line of Hep C drug candidates, destined to be part of an oral therapy regimen that will make the current use of interferon injections redundant. Even though there has been no evidence of cardiotoxicity in patients treated with IDX184, the FDA has expressed a concern regarding potential safety problems of the drug.

Gilead (GILD), the current leader in the next-gen Hep C drugs, is planning a Phase III study with a combination therapy of its NS5A and NS5B inhibitors. The FDA's recent caution regarding NS5 inhibitors might also affect Gilead's sprint toward the finish line. Novartis (NVS), which has recently joined the Hep C crowded waters with the $440m Enanta Pharmaceuticals deal, might also suffer from this new NS5-related safety issues.

About 180 million people worldwide are chronically infected with HCV. The global Hepatitis market was estimated at $6 billion in 2011 and is forecasted to grow to $20 billion until the end of the decade. The combination of this huge and growing market and insufficient efficacy of the current treatments has generated an immense interest among drug developers and quite a few deals.

The recent holdups in the NS5-related treatments suggest that the Hep C pipeline might need some variations. Several companies are developing alternative, non-NS5 inhibitor-related, Hep C treatments. Examples for such technologies are Transgene's (TRGNF.PK) TG4040 - a therapeutic Hep C vaccine based on a virus carrying and expressing three of the major Hepatitis C virus's non-structural proteins (NS3, NS4 and NS5B). TG4040 is currently in a phase II trial.

A different approach is taken by BioLineRx (BLRX) that develops BL-8020, an orally available treatment with a unique mechanism of action - inhibition of Hepatitis C virus-induced autophagy. In other words, BL-8020 acts on the host cell rather than the virus itself, thus greatly differentiating it from current and pipeline Hep C drugs. Preclinical studies have shown a synergistic effect of BL-8020, when combined with other anti-Hep C agents, which is likely to increase these agents' potency and reduce any adverse effects by enabling utilization of lower dosages.

With the current setbacks seen among Hep C pipeline frontrunners, additional rounds of licensing and acquisition deals in this area are expected, and companies that develop new and different approaches for Hep C treatment may greatly benefit from others' failures and should be closely watched by investors that follow this therapeutic field.

Disclosure: I have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.

IDX184 suffers setback in clinical trial....

Posted 8/16/12 on MarketWatch.com. Ouch. This makes Novartis look almost prescient in it's restructuring of it's relationship to Idenix. BMS-094, PSI-938 and IDX184 all share the same chemical structure - even if the cardiac event is unrelated to BMS-094 (hard to tell) I think the market will be wary regarding nucs sharing this structure.  

Idenix plunges 30% on HCV drug setback       08/16 10:43 AM

 BOSTON (MarketWatch) -- Shares of Idenix Pharmaceuticals (IDIX:$5.93,00$-2.38,00-28.64%) plunged 30% to $5.96 Thursday on news that the U.S. Food and Drug Administration has partially halted a Phase II clinical trial for its drug IDX184 over safety concerns. Idenix has been testing the product for the treatment of the hepatitis C virus, or HCV. The FDA placed a 'partial hold' on the trial pending the evaluation of reports that one of the patients taking the treatment had suffered a severe cardiac event. The FDA has also requested that Idenix provide additional patient data to help the agency with its evaluation. IDX184 belongs to a newer class of HCV drugs known as nucleotides. Earlier this month, shares of rival Bristol-Myers Squibb (BMY:$31.95,00$0.07,000.22%) slid almost 10% after the company announced it had suspended a Phase II study of its HCV nucleotide agent due to concerns that a patient had developed heart failure.

ImVacS 2012: Hepatitis C vaccine show promise

Press release posted 8/15/12 on Science Alert.com.au. Data presented on 8/13 at the Immunotherapies and Vaccine Summit (ImVacS) in Cambridge suggests a breakthrough in Hepatitis C vaccine research. Researchers took into account the highly error prone replication of HCV when creating this vaccine. By developing a vaccine that has only the most essential and highly conserved parts of the major viral surface protein, the body elicits antibodies that prevent both closely and distantly-related hepatitis C viruses from entering the cell and causing infection. Great promise involves great data however, of which we wait. 

Hep C vaccine breakthrough
 
WEDNESDAY, 15 AUGUST 2012

Hepatitis C affects around 200 million people around the world, and has a great ability to change its structure and evade the immune response, making it hard to vaccinate against. But the new vaccine candidate only contains the most essential, conserved parts of the viral surface protein, so it works on a variety of strains.

Currently undergoing formal preclinical studies, the vaccine is the result of breakthrough work done by Associate Professor Heidi Drummer with her team from the Institute’s Centre for Virology.

Hepatitis C affects around 200 million people around the world – a preventative vaccine has the potential to have a significant global health impact.

Associate Professor Drummer and her team have overcome a major hurdle in HCV vaccine research, developing a vaccine candidate that protects against a number of different HCV strains.

“Hepatitis C has a great ability to change its structure and evade the immune response. This makes vaccine development challenging,” Associate Professor Drummer said.

“Our vaccine is unique as it contains only the most essential, conserved parts of the major viral surface protein, eliciting antibodies that prevent both closely and distantly related hepatitis C viruses from entering cells, thereby preventing infection.”

Associate Professor Drummer unveiled the details about her HCV vaccine project at the prestigious Immunotherapeutics and Vaccine Summit (ImVacS) in Cambridge, Massachussets on August 13

Journal of Hepatology: "Myocardial injury in patients with chronic hepatitis C infection"

Abstract entitled "Myocardial injury in patients with chronic hepatitis C infection" posted online 8/13/12 in Journal of Hepatology.eu. A compelling study from Japan that definitely warrants further research into this phenomena and may add to the long list of extra-hepatic manifestations of having active, replicating Hepatitis C virus in the human body. This particular study found a link between myocardial perfusion and HCV.  Patients who achieved an SVR garnered better severity scores (SS) than prior to therapy. Relapsers saw improved SS scores while on therapy, but the scores worsened with the reappearance of virus.  If these results are confirmed, it adds to a growing base of evidence that dictates treating earlier instead of later. 

Article in Press

Myocardial injury in patients with chronic hepatitis C infection

Shigeo Maruyama, Masahiko Koda, Nobuyuki Oyake, Hidetoshi Sato, Yasuyoshi Fujii, Yutaka Horie, Yoshikazu Murawaki

Received 4 April 2012; received in revised form 13 July 2012; accepted 31 July 2012. published online 13 August 2012.

Accepted Manuscript

Abstract

Background & aims
The existence of a direct pathogenic link between hepatitis C virus (HCV) infection and myocardial injury has not been confirmed. We investigated the association between myocardial conditions and HCV in patients with HCV-related chronic hepatitis using thallium-201 myocardial scintigraphy.

Methods
In 217 consecutive cases of chronic HCV infection without overt heart disease, we performed electrocardiography (ECG), echocardiography, serum tests on myocardial injury and thallium-201 myocardial scintigraphy. Myocardial injury was confirmed by severity score (SS), which was calculated as the sum of thallium-201 perfusion defect scores. SS was followed prior to and after interferon (IFN) therapy in 200 patients with chronic hepatitis C.

Results
An abnormal ECG was found in 9% of the patients with chronic hepatitis C. Abnormal SS was found in 87% of chronic hepatitis C patients. Independent factors related to higher pretreatment SS were histology activity index score, serum HCV RNA titer and indocyanine green disappearance rate. After IFN therapy, SS was improved in patients with sustained virologic response. Among relapsers, the SS improved at the initial disappearance of HCV RNA, but SS worsened with reappearance of HCV RNA. The SS in non-viral responders did not change with IFN therapy.

Conclusions
Myocardial perfusion defects were found in 87% of the patients with chronic hepatitis C and improved with viral eradication from IFN therapy.

Medical Device industry makes a run at Pharma in the HCV space...

Posted 8/9/12 on The OTC Investor.com. Aethlon Medical is serious about it's Hemopurifier, a blood filtration device being looked at for several indications. If it is indeed capable of lowering HCV viral load to a point where pegylated interferon and ribavirin could be more effective and bump up response rates over 50% with less toxicity... and can do so at a cost lower than that of Direct Acting Antiviral combination therapy... Aethlon may be on to something. Yet another reason not to dismiss interferon just yet. 

Bristol’s Halted Hepatitis C Trial Reinforces Aethlon Medical’s Non-Toxic Therapy
By Paul Archie · Thursday, August 9th, 2012

In the biotechnology world, the sun rises and set around the two key words “safety” and “efficacy.”  A serious safety concern last week resulted in Bristol-Myers Squibb (NYSE: BMY) voluntarily halting its ongoing Phase 2 study of BMS-986094, a drug in development as a new indication for hepatitis C as part of the drug maker’s quest for an all-oral regimen for hep C.  A patient who had received a 200 milligram dose of the nucleotide polymerase inhibitor, or “nuke,” suffered heart failure; causing Bristol to stop the trial and begin evaluating participants to determine any correlation between the new drug and the heart damage.

In February, Bristol paid $2.5 billion to acquire Inhibitex, a 163-percent premium to the valuation of Inhibitex at that time, primarily to snag its hepatitis C drug candidate (then called INX-189).  The halted trial could seriously hamper Bristol in its race with Gilead (NASDAQ: GILD) and Abbott Labs (NYSE: ABT) to bring a new hepatitis C drug to market.  It is widely expected that an all-oral drug therapy for the liver disease that affects about 170 million people across the world will generate billions annually in sales.  It is the reason that Bristol paid the premium for Inhibitex and Gilead dished-out $11.1 billion last November to acquire Pharmassets and its hep C drug in development.

Investors that recognize the upside potential of new therapies for hepatitis C should be taking a close look at Aethlon Medical (OTCBB: AEMD), the maker of a first-in-class blood filtration device called the Hemopurifier®.  Recently released clinical research by Aethlon showed that the two most recent hepatitis C-infected patients to receive its Hemopurifier® therapy in combination with the standard of care peginterferon+ribavirin (PR) drug therapy achieved undetectable viral load at day-7.  In lay terms, that means that none of the hepatitis C virus was found in the patients’ bloodstream after seven days of treatment.

As an adjunct, the Aethlon Hemopurifier® selectively targets the rapid clearance of the hepatitis C virus from the entire circulatory system to improve benefit, dose, duration and tolerability of drug therapies.  Drugs, like that of Bristol, Gilead or Abbott, carry substantial safety risks because they are “additive” in nature, meaning that they are putting a foreign substance into the body.  Aethlon’s Hemopurifier® is “subtractive.”  It removes the virus through a proprietary filtering process, which does not carry the same, potentially deadly toxicity risks that can cost major pharma billions to finally realize.

The OTC Investor (http://s.tt/1kpgX)

'Viral Matters' HCV Drug Development discussion group on LinkedIn...

"Viral Matters" also has a home on LinkedIn as well, in the form of an HCV Drug Development discussion group. If you're a LinkedIn member, you can join the discussion here.