Peregrine Completes Patient Enrollment in Phase Ib HCV/HIV Coinfection Trial

TUSTIN, CA -- (MARKET WIRE) -- 01/31/11 -- Peregrine Pharmaceuticals, Inc. (NASDAQ: PPHM), a clinical-stage biopharmaceutical company developing first-in-class monoclonal antibodies for the treatment of cancer and viral infections, today announced the completion of enrollment in the company's Phase Ib dose escalation safety study of bavituximab in patients coinfected with chronic hepatitis C virus (HCV) and HIV. Previously this month, Peregrine initiated a randomized Phase II HCV trial to evaluate 12 weeks of therapy with bavituximab, a phosphatidylserine (PS)-targeting monoclonal antibody with immune-modulating potential, in combination with the antiviral drug ribavirin versus standard of care, pegylated interferon alpha 2a and ribavirin.

"Completion of enrollment in our third Phase I HCV trial is an important milestone for our bavituximab antiviral program, and sets the stage for reporting clinical data at a medical conference in the second quarter of this year while we begin to evaluate combination treatment with the antiviral agent ribavirin in a recently initiated study," said Steven W. King, president and chief executive officer of Peregrine. "Though standard treatment for chronic HCV may soon evolve with the introduction of new targeted antiviral drug candidates, immune stimulation with interferon remains a critical component of therapy. Preclinical data support the potential combination of bavituximab and ribavirin and we look forward to seeing how this combination initially compares to standard interferon and ribavirin treatment for 12 weeks in our Phase II study for patients infected with HCV."

In prior HCV clinical trials, bavituximab administered as monotherapy in single and multiple doses demonstrated a positive safety profile with no dose-limiting toxicities or serious adverse events. Bavituximab as a monotherapy also showed promising on therapy antiviral activity of up to 1.5 log viral load reduction.

Bavituximab may address a fundamental "immune evasion" mechanism exploited by many infectious pathogens. A growing body of published data from researchers worldwide shows that bavituximab's PS target, exposed on the surface of cells infected by viruses and protozoan parasites, suppresses the immune system's ability to fight disease. PS-targeting antibodies such as bavituximab bind to PS and block the immunosuppressive signals created by the target, thereby allowing the immune system to mount a robust immune response against the pathogen.

About the Phase Ib HCV Trial Peregrine's open-label, dose escalation safety study is designed to assess the safety and of bavituximab in up to 24 patients chronically infected with HCV and HIV. Patient cohorts received ascending dose levels of bavituximab weekly for up to 8 weeks. Primary endpoints include safety and pharmacokinetics, and secondary endpoints will measure HCV and HIV RNA by PCR. For further information about Peregrine's HCV trials, please visit www.peregrinetrials.com or http://www.clinicaltrials.gov/ct2/results?term=bavituximab.

About HCV According to the U.S. Centers for Disease Control and Prevention, an estimated 3.2 million individuals in the United States have chronic hepatitis C virus (HCV) infection. Chronic HCV infection is a serious disease that can result in long-term health problems, including liver damage, liver failure, liver cancer, or death. It is the leading cause of cirrhosis and liver cancer and the most common reason for liver transplant in the United States. Approximately 8,000 to 10,000 people die every year from HCV-related liver disease.

About Bavituximab's Antiviral Approach Bavituximab is the first in a new class of patented antibody therapeutics that target and bind to phosphatidylserine (PS), a specific phospholipid component of cell membranes. Bavituximab helps reactivate and direct the body's immune system to destroy infected cells and virus particles that exhibit this specific phospholipid on their surface. Since their target is host-derived rather than pathogen-derived, PS-targeting antibodies have the potential for broad-spectrum antiviral activity and are also expected to be much less susceptible to the viral mutations that often lead to drug resistance.

Researchers have found that PS is exposed on the outer membrane of cells infected with HCV, HIV, influenza, herpes viruses, hemorrhagic fever viruses, respiratory syncytial virus, measles as well as other viruses. A growing body of scientific publications, including Nature Medicine and The Journal of Experimental Medicine, has highlighted data on the role of PS and Peregrine's PS-targeting therapies in infectious diseases.

About Peregrine Pharmaceuticals Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company with a portfolio of innovative monoclonal antibodies in clinical trials for the treatment of cancer and serious viral infections. The company is pursuing multiple clinical programs in cancer and hepatitis C virus infection with its lead product candidate bavituximab and novel brain cancer agent Cotara®. Peregrine also has in-house cGMP manufacturing capabilities through its wholly-owned subsidiary Avid Bioservices, Inc. (www.avidbio.com), which provides development and biomanufacturing services for both Peregrine and outside customers. Additional information about Peregrine can be found at www.peregrineinc.com.

Safe Harbor Statement: Statements in this press release which are not purely historical, including statements regarding Peregrine Pharmaceuticals' intentions, hopes, beliefs, expectations, representations, projections, plans or predictions of the future are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. The forward-looking statements involve risks and uncertainties including, but not limited to, the risk that results from the Phase Ib or Phase II HCV trials will not be consistent with results experienced in earlier HCV clinical trials and preclinical studies, the risk that investigators may experience delays in patient enrollment, risk that results may not support registration filings with the U.S. Food and Drug Administration, and the risk that Peregrine may not have or raise adequate financial resources to complete the planned clinical programs. Factors that could cause actual results to differ materially or otherwise adversely impact the company's ability to obtain regulatory approval for its product candidates include, but are not limited to, uncertainties associated with completing preclinical and clinical trials for our technologies; the early stage of product development; the significant costs to develop our products as all of our products are currently in development, preclinical studies or clinical trials; obtaining additional financing to support our operations and the development of our products; obtaining regulatory approval for our technologies; anticipated timing of regulatory filings and the potential success in gaining regulatory approval and complying with governmental regulations applicable to our business. Our business could be affected by a number of other factors, including the risk factors listed from time to time in the company's SEC reports including, but not limited to, the annual report on Form 10-K for the year ended April 30, 2010 and the quarterly report on Form 10-Q for the quarter ended October 31, 2010. The company cautions investors not to place undue reliance on the forward-looking statements contained in this press release. Peregrine Pharmaceuticals, Inc. disclaims any obligation, and does not undertake to update or revise any forward-looking statements in this press release.

Anadys Initiates Dosing in Phase IIb Study of ANA598

The race for next gen DAA compounds continues. Given the AE's, dosing difficulty and the sequential therapy void associated with the upcoming Telaprevir and Boceprevir compounds, the market looks lucrative.

SAN DIEGO, Jan. 26, 2011 /PRNewswire/ -- Anadys Pharmaceuticals, Inc. (Nasdaq: ANDS) announced today that dosing has begun in the Phase IIb study of ANA598 in combination with pegylated interferon and ribavirin in hepatitis C patients. ANA598, the Company's direct-acting antiviral, is being tested in both treatment-naive patients and patients who failed a prior course of HCV therapy with interferon and ribavirin. Approximately 275 patients are expected to be enrolled in the study. The primary endpoint of the study is Sustained Virological Response 24 weeks after patients complete treatment, known as SVR24.

The Company expects to receive Week 8 antiviral response data for treatment-naive patients by the end of the second quarter of 2011, Week 12 antiviral response data for treatment-experienced patients in the third quarter of 2011 and Week 24 antiviral response data for both groups in the fourth quarter of 2011.

About Anadys

Anadys Pharmaceuticals, Inc. is a biopharmaceutical company dedicated to improving patient care by developing novel medicines for the treatment of hepatitis C. The Company believes hepatitis C represents a large unmet medical need in which meaningful improvements in treatment outcomes may be attainable with the introduction of new medicines. Anadys is conducting a Phase IIb study of ANA598, the Company's DAA, added to current standard of care for the treatment of hepatitis C. The Company is also preparing to resume clinical development of ANA773, the Company's oral, small-molecule inducer of endogenous interferons that acts via the Toll like receptor 7, or TLR7, pathway in hepatitis C.

Safe Harbor Statement

Statements in this press release that are not strictly historical in nature constitute "forward-looking statements." Such statements include, but are not limited to, references to Anadys' expectations regarding the timing of receipt of data from the study and the ability to achieve the primary endpoint of the study. Such forward-looking statements involve known and unknown risks, uncertainties and other factors, which may cause Anadys' actual results to be materially different from historical results or from any results expressed or implied by such forward-looking statements. For example, the results of preclinical and early clinical studies may not be predictive of future results, and Anadys cannot provide any assurances that ANA598 will not have unforeseen safety issues, will have favorable results in ongoing or future clinical trials or will receive regulatory approval. In addition, Anadys' results may be affected by competition from other biotechnology and pharmaceutical companies, its effectiveness at managing its financial resources, its ability to enter into transactions around its product candidates, its ability to successfully develop and market products, difficulties or delays in its non-clinical studies or clinical trials, difficulties or delays in manufacturing its clinical trials materials, the scope and validity of patent protection for its products, regulatory developments and its ability to obtain additional funding to support its operations. Risk factors that may cause actual results to differ are more fully discussed in Anadys' SEC filings, including Anadys' Form 10-Q for the quarter ended September 30, 2010. All forward-looking statements are qualified in their entirety by this cautionary statement. Anadys is providing this information as of this date and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.


SOURCE Anadys Pharmaceuticals, Inc.

Scientists find connection between anemia and ITPA variants.

Scientists have discovered two functional variants in the inosine triphosphatase (ITPA) gene that protect patients with hepatitis C virus (HCV) against anemia brought on by antiviral treatment.

The ability to identify those patients protected against treatment-induced anemia will ensure completion of antiviral therapy and successful elimination of the virus.

Alessandra Mangia, from Casa Sollievo della Sofferenza Hospital in Italy, and colleagues evaluated the association between ITPA variants and anemia in a cohort of 238 Caucasian patients treated with variable pegIFN and weight-based doses of RBV. The research team found that the ITPA variants were strongly and independently associated with protection from anemia, but did not provide an increase in sustained virological response.

"When anemia develops only four weeks after the start of treatment, physicians are required to immediately reduce ribavirin dosages. This early reduction will affect the overall duration of treatment which, with the combination of pegIFN and RBV, lasts 24 weeks for patients infected with HCV genotypes two and 3 (G2/3) and 48 weeks for patients with HCV genotype one (G1) infection. Currently, only the use of the drug erythropoietin (EPO)-an expensive drug that due to its high cost cannot be reimbursed in several countries-might prevent unsuccessful antiviral treatment in these cases," explained Mangia.

"Our findings demonstrated that ITPA variants are strongly associated with protection from week four anemia and help us in selecting in advance who will need early ribavirin dose reduction and possibly supportive EPO treatment. This may lead to a more rational use of economical resources and to an individualized use of supportive EPO treatment," concluded Mangia.

"Patients with a genetic profile that included the two ITPA variants may be safely administered higher doses of RBV, increasing the likelihood of HCV elimination after treatment-an important finding given that to achieve viral clearance high dosages of RBV need to be used in the early phases of treatment."

A related study led by Fumitaka Suzuki, from Toranomon Hospital in Japan found similar results in its cohort of 61 Japanese patients with HCV.

Patients in this study received a triple therapy of pegINF, RBV and the protease inhibitor, telaprevir. Suzuki and colleagues found that ITPA variants impacted blood levels; however a sustained virological response could be achieved with careful monitoring of anemia and prompt adjustment of RBV dose. The authors suggest that future investigation of the influence of ITPA gene variants on RBV-induced anemia are needed on larger scales and on patients of various ethnicities.
The findings will be published in Hepatology.

Vertex's Senior Vice President of Sales is no more...

The word on the street is that Joe Cozzolino the Senior VP of Sales for Vertex is no longer with the company as of today, 1/26/10 for reasons yet unknown. What does it mean for a company fully ensconced in the transition from a R&D company to a full-fledged commercial entity when one of the key strategists leaves the fold? The timing isn't terrific - Vertex is counting on a decision on the approval of it's HCV protease inhibitor Telaprevir on May 23rd with a June launch date. That's four months to scramble to fill a large leadership gap. If Vertex displays the agility it had in it's younger days, it can be done. If the organization succumbs to the corporate cultural flux and the internal inertia it's displayed in it's post Josh Boger-era, it would leave quite a bit of Vertex exposed to Merck's commercial prowess. Either way, this will certainly become a graduate school case study somewhere.

Xconomy weighs in on ZymoGenetics and what could have been....

How ZymoGenetics Coulda Been a Contender: The Big Break That Came Too Late

Luke Timmerman 1/25/11

ZymoGenetics, if it had stayed an independent company in Seattle, would be worth tens of millions of dollars more today than what it was in September when it agreed to be acquired by Bristol-Myers Squibb (NYSE: BMY).

Bristol clearly scored a big break with its new ZymoGenetics assets on December 21, about two months after it closed the books on its $885 million acquisition of the venerable Seattle biotech.

If it had still been an independent biotech, the value of ZymoGenetics would have soared that day when Cambridge, MA-based Vertex Pharmaceuticals announced that, essentially, it had failed to make ZymoGenetics’ lead drug candidate obsolete. On that day, Vertex (NASDAQ: VRTX) said it was unable to eradicate one of backbone components of hepatitis C therapy in a high profile clinical trial.

Vertex is blazing a new trail in the field with a potent new oral pill that generates unprecedented cure rates when given in combination with two standard treatments—pegylated interferon alpha and ribavirin. Vertex was hoping to raise the bar even higher, to find out if its lead molecule, telaprevir, could be combined into a new cocktail regimen that Vertex hoped would kick old-school interferon into the dustbin of history. Doctors and patients have been yearning for a way to get rid of interferon, which causes nasty flu-like symptoms that make patients feel awful for months, which discourages most patients from seeking treatment.

ZymoGenetics, knowing this well, had developed a genetically modified version of interferon, which it called pegylated interferon lambda. This new form of interferon was designed to kill the hepatitis C virus just like the older version of interferon, but without the flu-like side effects. Results from early clinical trials were so promising that ZymoGenetics was able to entice Bristol to sign a $1.1 billion partnership to co-develop the drug in January 2009.

But many on Wall Street weren’t impressed. They had fallen head over heels for Vertex’s new molecule, insisting that ZymoGenetics and Bristol were wasting their time with a new type of interferon. Vertex, they said, was coming along with a cocktail approach of new oral pills that would get rid of interferon, meaning any improvement on old-school interferon would soon be irrelevant. While many doctors, and companies like Vertex still hope it will be possible to do this, the latest clinical trial failure makes it clear that interferon will be part of the standard treatment regimen for years. That means the drug Bristol acquired from ZymoGenetics has a chance to integrate itself into a new standard of care, at a moment when awareness has never been higher among an estimated 6 million U.S. and European patients with this liver-damaging condition.

Former ZymoGenetics CEO Doug Williams, who recently took a new job as head of R&D at Weston, MA-based Biogen Idec, acknowledged in a recent interview that the failure of Vertex’s combination trial would have been a positive event for ZymoGenetics and its pegylated interferon lambda program. He stopped short of saying that Wall Street would have perceived the development in a way that would have boosted ZymoGenetics’ stock price.

“Certainly some people would have come off the fence and perhaps started to believe that interferons will be really hard to get rid of,” Williams says. “I’m certainly of the mind that it will be extremely difficult to get rid of interferon, and achieve [cure rates] currently seen.”

He added: “I gotta believe it would have been viewed as a net positive, but the degree to which it would have been reflected in the stock price, I don’t think anybody can say that.”

David Miller, the president of Biotech Stock Research in Seattle, who criticized ZymoGenetics for selling the company at a bargain price, said he believes investors would have given the company credit. An estimated 6 million patients in the U.S. and Europe have hepatitis C, and many of them are expected to start seeking treatment in 2011, now that a new wave of protease inhibitors like Vertex’s telaprevir and Merck’s boceprevir are being primed to hit the market later this year. The existing interferons from Roche and Merck made up a combined market worth more than $2 billion in 2009, even before the more-effective protease inhibitors came along to spur more interest in hepatitis C therapy.

ZymoGenetics could have seen its stock climb another $2 to $3 a share if it had still been an independent company when the Vertex news hit the wire on December 21, Miller says.

“Smart money was moving toward ZymoGenetics,” Miller says. The latest clinical trial failure of the no-interferon regimen, Miller says, “would have been huge for ZymoGenetics. People were starting to understand that interferons aren’t going anyway anytime soon. This press release (from Vertex) would have cemented that.”

Now that doctors are getting accustomed to seeing hepatitis C cure rates in the neighborhood of 70 to 75 percent of patients who take the combo regimen of the Vertex drug, plus interferon and ribavirin, it’s unlikely they will ever sacrifice even a few percentage points of effectiveness just to get rid of interferon’s side effects, Williams says. That means the bar is high for any oral pill cocktail regimen that aspires to get rid of interferon. It’s certainly possible that the combination of doses, and schedules, could coalesce to make that happen, but it will take years to figure out in clinical trials, Williams says.

Given that was what ZymoGenetics management was betting on with their new interferon, and that its thesis was essentially validated on December 21st, I had to ask Williams if he regrets selling the company for less than a billion dollars. He said no.

“I don’t look back on these sorts of decisions,” Williams says. “You make the decision you have to make at the time with the information you have available to you at the time. I feel we made the right decision at the right time.”

Luke Timmerman is the National Biotech Editor of Xconomy, and the Editor of Xconomy Seattle. You can e-mail him at ltimmerman@xconomy.com, or follow him at twitter.com/ldtimmerman.

Telaprevir FDA review date set for May 23, 2011.

The FDA review date for Telaprevir has been set for May 23rd of this year. Merck still hasn't stated (as of 1/20/11) exactly when their review is taking place, but there is no shortage of interest in the investment community on who gets to market first. Given the advancing pipelines of the competition who will strive to offer increasingly tolerable drugs with less dosing frequency and perhaps better efficacy, I give both Merck and Vertex a year to a year and one half before HCV treaters start another period of 'watch and wait' - essentially holding patients from treatment who are at low risk for progression of disease - for these new compounds to make it to market.

Thursday January 20, 2011 - 07:30 AM EST
Business Wire News Releases
Released By Vertex Pharmaceuticals Incorporated

Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) announced today that the U.S. Food and Drug Administration (FDA) has accepted the New Drug Application (NDA) for telaprevir and granted the company’s request for six-month Priority Review. Telaprevir is Vertex’s lead medicine in development for people with genotype 1 chronic hepatitis C. The FDA grants Priority Review to medicines that offer major advances in treatment or provide a treatment where no adequate therapy exists. A target review date of May 23, 2011 is set under the Prescription Drug User Fee Act (PDUFA) for the FDA’s approval decision, which is four months earlier than the standard review time of 10 months.

Additionally, Vertex today announced the completion of a New Drug Submission (NDS) to the Therapeutic Product Directorate (TPD) of Health Canada seeking approval for telaprevir in Canada. Telaprevir was also granted Priority Review in Canada, which allows for faster review for promising medicines that address life-threatening or severely debilitating conditions and for which there are few effective therapies already available. Standard review in Canada takes 18 months or more and Priority Review typically shortens the review time to approximately six to nine months.

In December 2010, Janssen-Cilag International NV announced that the European Medicines Agency (EMA) accepted telaprevir for accelerated assessment in Europe, which is granted to new medicines of major public health interest.

“Data from Phase 3 studies showed that when compared to currently available medicines, telaprevir-based combination therapy nearly doubled viral cure rates and cut treatment time in half for the majority of patients new to treatment,” said Peter Mueller, Ph.D., Chief Scientific Officer and Executive Vice President of Global Research and Development at Vertex. “We look forward to working with the FDA and Health Canada to make telaprevir available as quickly as possible for people with hepatitis C.”

Data to Support the Telaprevir Submissions

The regulatory submissions in the United States, Canada and Europe are supported by data from three Phase 3 studies, known as ADVANCE, ILLUMINATE and REALIZE, which evaluated up to 12 weeks of telaprevir in combination with Pegasys® (pegylated-interferon alfa-2a) and Copegus® (ribavirin) in people chronically infected with genotype 1 hepatitis C virus (HCV) who were new to treatment as well as those who were treated before with currently available medicines but did not achieve a sustained viral response (SVR, or viral cure). In these studies, treatment with telaprevir-based combination therapy resulted in significantly higher viral cure rates compared to approved medicines, regardless of prior treatment experience, race or stage of liver disease. Up to 75 percent of people new to treatment achieved a viral cure with telaprevir-based therapy. The majority of these people were able to complete their course of treatment at six months – half the time needed with currently available medicines. Among those who did not achieve a viral cure with a prior treatment course of currently available medicines, Phase 3 data showed that telaprevir-based combination therapy resulted in viral cure rates three to five times higher compared to re-treatment with currently available medicines. The safety and tolerability results of telaprevir-based combination therapy were consistent across the Phase 3 studies. The most common adverse events regardless of treatment regimen were rash, fatigue, pruritis, headache, nausea, anemia, insomnia, diarrhea, flu-like symptoms and pyrexia, with the majority being mild or moderate in severity.

Vertex provided a summary of Phase 3 results, including SVR and safety data for telaprevir, in its November 23, 2010 press release announcing the NDA submission.

About Telaprevir

Telaprevir is an investigational, oral inhibitor that acts directly on the HCV protease, an enzyme essential for viral replication. To date, more than 2,500 people with genotype 1 hepatitis C have received telaprevir in Phase 2 and Phase 3 studies.
Vertex is developing telaprevir in collaboration with Tibotec BVBA and Mitsubishi Tanabe Pharma. Vertex has rights to commercialize telaprevir in North America. Through its affiliate, Janssen, Tibotec has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries.

About Hepatitis C

Hepatitis C is a serious liver disease caused by the hepatitis C virus, which is spread through direct contact with the blood of infected people and ultimately affects the liver.1 Chronic hepatitis C can lead to serious and life-threatening liver problems, including liver damage, cirrhosis, liver failure or liver cancer.1 Though many people with hepatitis C may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain.1 Approximately 60 percent of genotype 1 patients who undergo an initial 48-week regimen with pegylated-interferon and ribavirin, the currently approved medicines, do not achieve SVR,2,3,4 or viral cure.5 If treatment is not successful and a person does not achieve a viral cure, they remain at an increased risk for progressive liver disease.6,7,8.9,10
Hepatitis C in the United States

Up to 3.9 million people in the United States have chronic hepatitis C and 75 percent of them are unaware of their infection.11 The majority of people with hepatitis C in the U.S. were born between 1946 and 1964, accounting for two of every three people with chronic hepatitis C.10 Hepatitis C is the leading cause of liver transplantations in the U.S. and is reported to contribute to 4,600 to 12,000 deaths annually.7 By 2029, total annual medical costs in the U.S. for people with hepatitis C are expected to more than double, from $30 billion in 2009 to approximately $85 billion.10

Hepatitis C in Canada

Approximately 250,000 people in Canada have chronic hepatitis C and more than a third of them do not know they are infected.12 Three provinces account for 80 percent of hepatitis C infections in Canada: Ontario (42 percent), British Columbia (22 percent) and Quebec (16 percent).13 Each year up to 5,000 people are newly infected with hepatitis C and in 2007 alone, nearly 8,000 people were infected.12, 13 In 2010, the annual cost of hepatitis C due to medical treatment and lost productivity in Canada was estimated to reach $1 billion.14 By 2022, the number of hepatitis C-related deaths is expected to increase by one-third.15

Additional resources for media are available at: http://investors.vrtx.com/press.cfm.
PEGASYS® and COPEGUS® are registered trademarks of Hoffman-LA Roche.


About Vertex

Vertex creates new possibilities in medicine. Our team aims to discover, develop and commercialize innovative therapies so people with serious diseases can lead better lives.
Vertex scientists and our collaborators are working on new medicines to cure or significantly advance the treatment of hepatitis C, cystic fibrosis, epilepsy and other life-threatening diseases.

Founded more than 20 years ago in Cambridge, MA, we now have ongoing worldwide research programs and sites in the U.S., U.K. and Canada.
About Vertex in Canada

In 2009, Vertex established a research and development site in Laval, Quebec through the acquisition of Virochem Pharma, Inc. Vertex is expanding its existing research and development infrastructure with the addition of commercial and medical teams to support the potential launch of telaprevir in Canada.
For more information and to view Vertex's press releases, please visit www.vrtx.com.

(VRTX - GEN)
References:
1 Centers for Disease Control and Prevention. Hepatitis C Fact Sheet: CDC Viral Hepatitis. Available at: http://www.cdc.gov/hepatitis/HCV/PDFs/HepCGeneralFactSheet.pdf. Accessed May 25, 2010.
2 Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358:958-965.
3 Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975-982.
4 McHutchison JG, Lawitz EJ, Shiffman ML, et al; IDEAL Study Team. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med. 2009;361:580-593.
5 Ghany MG, Strader DB, Thomas DL, Seeff, LB. Diagnosis, management and treatment of hepatitis C; An update. Hepatology. 2009;49 (4):1-40.
6 Morgan TR, Ghany MG, Kim HY, Snow KK, Lindsay K, Lok AS. Outcome of sustained virological responders and non-responders in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial. Hepatology. 2008;50(Suppl 4):357A (Abstract 115).
7 Davis GL, Alter MJ, El-Serag H, Poynard T, Jennings LW. Aging of hepatitis C virus (HCV)-infected persons in the United States: A multiple cohort model of HCV prevalence and disease progression. Gastroenterology. 2010;138:513-521.
8 Volk MI, Tocco R, Saini S, Lok, ASF. Public health impact of antiviral therapy for hepatitis C in the United States. Hepatology. 2009;50(6):1750-1755.
9 Veldt BJ, Heathcote J, Wedmeyer H. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Annals of Internal Medicine. 2007; 147: 677-684.
10 Pyenson B, Fitch K, Iwasaki K. Consequences of hepatitis C virus (HCV): Costs of a baby boomer epidemic of liver disease. http://www.natap.org/2009/HCV/051809_01.htm. Updated May 2009. This report was commissioned by Vertex Pharmaceuticals, Inc.
11 Institute of Medicine of the National Academies. Hepatitis and liver cancer: a national strategy for prevention and control of hepatitis B and C. Colvin HM and Mitchell AE, ed. http://www.iom.edu/Reports/2010/Hepatitis-and-Liver-Cancer-A-National-Strategy-for-Prevention-and-Control-of-Hepatitis-B-and-C.aspx. Updated January 11, 2010. Accessed May 25, 2010.
12 Public Health Agency of Canada. Hepatitis C: Get the facts. You could have it and not know it. http://www.phac-aspc.gc.ca/hepc/pubs/getfacts-informezvous/index-eng.php. Updated September 21, 2010. Accessed January 18, 2011.
13 Public Health Agency of Canada. Modeling the incidence of prevalence of hepatitis C infection and its sequelae in Canada, 2007. http://www.phac-aspc.gc.ca/sti-its-surv-epi/model/results-eng.php. Updated October 20, 2010. Accessed January 18, 2011.
14 Public Health Agency of Canada. A renewed public health response to address hepatitis C: A summary report of the priority-setting process and strategic framework to action. http://www.phac-aspc.gc.ca/hepc/sr-rs/pdf/srhepc-eng.pdf. Updated June 2009. Accessed January 2011.
15 Sherman M, Sharfran S, Burak K, et al. Management of chronic hepatitis C consensus guidelines. Can J Gastroenterol. 2007;21 (Suppl C):25C-34C.

The Death of American Journalism - Follow The Money....

I'm old enough to remember when newspapers still had money and paid journalists to report the news. Better were the investigative journalists that really dug in and gave you the story behind the story. Those are hard to come by these days. Some of that still remains, but there is a great deal of 'content' both on and offline that's just cut n' pasted from AP who cut n' pasted from a PR firm. I've seen the below several times over the past two days, this happens to be from the Los Angeles Times. Now I don't blame them, it's cheaper than paying a journalist and when you're looking at the bottom line, hard journalism goes out the window. Back in my day, a journalist would do due diligence. A journalist would research and call on the carpet items of news that did not jive. I'm Joe Public and I'm reading that the CDC is beginning a study to see what comes of testing for HCV amongst Baby Boomers. I think, "Wow, the CDC is really looking out for the public interest!". What the article doesn't tell you is that the study is being funded by the Viral Hepatitis Action Coalition, part of the "CDC Foundation" which is a convenient nonprofit partner of the CDC. "The CDC Foundation helps CDC do more, faster by forging effective partnerships between CDC and individuals, corporations and foundations to fight threats to health and safety." according to their press release on 1/12 of this year. The corporations behind the Viral Hepatitis Action Coalition? Vertex Pharmaceuticals, Merck, Gilead Sciences and OraSure Technologies, Inc. Would any of these companies benefit financially from such a study? Definitely. So that may or may not make a difference to you, but wouldn't you like to know? Or that perhaps the Viral Hepatitis Action Coalition and one or more of the corporations that help fund it share the same PR firm? This is where public health and corporate profits coalesce. Why just the effort to test Baby Boomers and not a mass effort to test other populations that have equally as high or higher risk of being infected? The indigent, the incarcerated, those known to use needle-injected drugs for example? Is it because they have less resources to pay for expensive drugs? Less risk factors for progression of disease? Would cost the government coffers far too much to even think about? I don't know, but these questions are certainly worth asking. But you won't find the tough questions being asked in the LA Times or any number of reputable news outlets.

Where are Woodward and Bernstein when you need them?? Check your sources!

latimes.com
HEALTHBEAT: New drugs take aim at hepatitis C, spur debate on whether to test baby boomers

LAURAN NEERGAARD

AP Medical Writer

12:04 AM PST, January 18, 2011



WASHINGTON (AP) — There's new hope for an overlooked epidemic: Two powerful drugs are nearing the market that promise to help cure many more people of liver-attacking hepatitis C — even though most who have the simmering infection don't know it yet.

Surprisingly, two-thirds of hepatitis C sufferers are thought to be baby boomers who've harbored since their younger, perhaps wilder, years avirus that can take two or three decades to do its damage.

What could be a treatment revolution is spurring the government to consider if it's time to start screening aging baby boomers for hepatitis C, just like they get variouscancer checks.

"We're entering a whole new era of therapy," says Dr.John Ward, hepatitis chief at the Centers for Disease Control and Prevention. "We really want to begin that clarion call for action for this population who's at risk."

Today's two-drug treatment for hepatitis C cures only about 40 percent of people with the most common variety of the virus, and causes some grueling side effects. Now major studies show that adding a new drug —eitherVertex Pharmaceuticals' telaprevir or Merck & Co.'s boceprevir — can boost those cure rates as high as 75 percent. And they allow some people to cut treatment time in half, to six months, thus lessening how long they must deal with those side effects.

If the Food and Drug Administration approves the drugs — a decision widely expected this summer — they would be the first that work by directly targeting the hepatitis C virus. Specialists draw comparisons to the early 1990s when potent combination therapies emerged to treat AIDS. Many recently diagnosed patients are postponing therapy to await these new drug cocktails in hopes of a better chance at a faster cure, says Dr. Paul Pockros, hepatology chief at the Scripps Clinic in La Jolla, Calif., who helped test telaprevir.

However, the bigger impact could come if more people get tested for hepatitis C, ablood-borne virus. It's often stigmatized as a risk only to people who inject illegal drugs. But the virus could have begun festering from a blood transfusion before 1992, when testing of the blood supply began.

Lapses in infection control in health facilities still occasionally expose people today. So could even a one-time experiment with drugs way back in college, something doctors are reluctant to ask a now middle-aged, button-downed patient to reveal, says Ward.

"It cuts across every segment of society," adds Dr. Arun Sanyal ofVirginia Commonwealth University, past president of the American Association for the Study of Liver Diseases. "I can tell you our hepatitis C treatment clinic is a great social equalizer."

About 3.2 million Americans, and 170 million people worldwide, have chronic hepatitis C. In the U.S., new infections have dropped dramatically — although the disease's toll is rising as people infected decades earlier reach ages where their livers start showing damage. Hepatitis C already is a leading cause ofliver transplants, and it kills about 12,000 U.S. patients a year, a number expected to triple within 20 years.

Most people find out they're infected like Brian Graham of Briarcliff Manor, N.Y., during a routine check-up that spotted elevated liver enzymes. He'd never heard of hepatitis C and had no obvious risk factors. But tests showed the virus had begun to scar his liver. So over the last decade he tried three rounds of traditional treatments, with increasingly tough side effects, to no avail.

"I didn't want to die of liver disease or cancer or suffer the prospect of having to tee up for a liver transplant. Scary stuff," says Graham, now 56.

Enter the new drugs. They work by blocking an enzyme named protease that's key for the virus to reproduce. But they must be taken together with standard medications — ribavirin pills plus injections of interferon-alpha — that are thought to boost theimmune system.

According to studies presented at a recent medical meeting, 67 percent to 75 percent of patients given treatment including either boceprevir or telaprevir, respectively, had what doctors call a cure. That's defined as no sign of the hepatitis C virus six months after their last dose. Importantly, only about a quarter of black patients are helped by standard therapy but adding one of the new drugs more than doubled their cure rates.

People getting their first-ever treatment did best, but the studies also found improvements in hard-to-treat patients like Graham.

"The fourth time did the trick," says Graham, who volunteered for an early telaprevir study and says he's been hepatitis-free for three years.

The new drugs do add side effects to the flulike symptoms and other complaints of existing treatment. Telaprevir's main risk is a rash that is sometimes severe, and boceprevir's is anemia.

"The future looks very bright beyond telaprevir and boceprevir," notes Dr. Fred Poordad of Cedars-Sinai Medical Center inLos Angeles, who has studied both drugs and consults for several companies. He points to additional drugs in earlier-stage testing that promise to target more types of hepatitis C and perhaps eventually allow for pill-only, interferon-free treatment.

Manufacturers haven't said how much the new drugs will add to the price of treatment that already can cost $30,000, albeit far cheaper than a liver transplant.

A stickier issue: Not everyone suffers serious liver damage and it's hard to predict who will, raising questions about exactly who needs treatment even as drug companies help push for more screening."

That's a concern, acknowledges Jeff Levi of the nonprofit Trust for America's Health, also a screening proponent. But when to treat is a doctor-patient decision, and "anyone with chronic infection you do want to be monitoring so you can intervene at the right moment," he adds.

Plus, people with hepatitis C should avoid alcohol and consider other liver-protection steps — and know how to avoid infecting others, he stresses.

Stay tuned: The CDC has begun a study at four hospitals — inNew York, Detroit, Houston and Birmingham, Ala. — to see if a one-time hepatitis C test for baby boomers makes sense. Among the boomers, black men in their 50s are at particular risk. CDC plans new guidelines next year.

Meanwhile, "start that conversation" at a routine doctor's visit by asking about hepatitis C risks and testing, Ward advises boomers.

To test or not to test? HCV testing of baby boomer population begins the great debate.

Articles like this give me mixed feelings with their exuberance - Telaprevir and Boceprevir are definitely ground-breaking drugs, but aren't the answer for a lot of folks. Both drugs have major side effects, dosing frequency issues, pill burden and a great propensity for untrained or negligent treaters to screw-up. I do like the CDC's initiative to test for HCV in the Baby Boomer population... but that opens up a whole new debate... whose going to pay for all the tests and, ultimately, treatment?

WASHINGTON — There's new hope for an overlooked epidemic: Two powerful drugs are nearing the market that promise to help cure many more people of liver-attacking hepatitis C — even though most who have the simmering infection don't know it yet.

Surprisingly, two-thirds of hepatitis C sufferers are thought to be baby boomers who've harboured since their younger, perhaps wilder, years a virus that can take two or three decades to do its damage.

What could be a treatment revolution is spurring the government to consider if it's time to start screening aging baby boomers for hepatitis C, just like they get various cancer checks.
"We're entering a whole new era of therapy," says Dr. John Ward, hepatitis chief at the Centers for Disease Control and Prevention. "We really want to begin that clarion call for action for this population who's at risk."

Today's two-drug treatment for hepatitis C cures only about 40 per cent of people with the most common variety of the virus, and causes some gruelling side effects. Now major studies show that adding a new drug —either Vertex Pharmaceuticals' telaprevir or Merck & Co.'s boceprevir — can boost those cure rates as high as 75 per cent. And they allow some people to cut treatment time in half, to six months, thus lessening how long they must deal with those side effects.

If the Food and Drug Administration approves the drugs — a decision widely expected this summer — they would be the first that work by directly targeting the hepatitis C virus. Specialists draw comparisons to the early 1990s when potent combination therapies emerged to treat AIDS. Many recently diagnosed patients are postponing therapy to await these new drug cocktails in hopes of a better chance at a faster cure, says Dr. Paul Pockros, hepatology chief at the Scripps Clinic in La Jolla, Calif., who helped test telaprevir.

However, the bigger impact could come if more people get tested for hepatitis C, a blood-borne virus. It's often stigmatized as a risk only to people who inject illegal drugs. But the virus could have begun festering from a blood transfusion before 1992, when testing of the blood supply began.

Lapses in infection control in health facilities still occasionally expose people today. So could even a one-time experiment with drugs way back in college, something doctors are reluctant to ask a now middle-aged, button-downed patient to reveal, says Ward.

"It cuts across every segment of society," adds Dr. Arun Sanyal of Virginia Commonwealth University, past president of the American Association for the Study of Liver Diseases. "I can tell you our hepatitis C treatment clinic is a great social equalizer."

About 3.2 million Americans, and 170 million people worldwide, have chronic hepatitis C. In the U.S., new infections have dropped dramatically — although the disease's toll is rising as people infected decades earlier reach ages where their livers start showing damage. Hepatitis C already is a leading cause of liver transplants, and it kills about 12,000 U.S. patients a year, a number expected to triple within 20 years.

Most people find out they're infected like Brian Graham of Briarcliff Manor, N.Y., during a routine check-up that spotted elevated liver enzymes. He'd never heard of hepatitis C and had no obvious risk factors. But tests showed the virus had begun to scar his liver. So over the last decade he tried three rounds of traditional treatments, with increasingly tough side effects, to no avail.

"I didn't want to die of liver disease or cancer or suffer the prospect of having to tee up for a liver transplant. Scary stuff," says Graham, now 56.

Enter the new drugs. They work by blocking an enzyme named protease that's key for the virus to reproduce. But they must be taken together with standard medications — ribavirin pills plus injections of interferon-alpha — that are thought to boost the immune system.

According to studies presented at a recent medical meeting, 67 per cent to 75 per cent of patients given treatment including either boceprevir or telaprevir, respectively, had what doctors call a cure. That's defined as no sign of the hepatitis C virus six months after their last dose. Importantly, only about a quarter of black patients are helped by standard therapy but adding one of the new drugs more than doubled their cure rates.

People getting their first-ever treatment did best, but the studies also found improvements in hard-to-treat patients like Graham.

"The fourth time did the trick," says Graham, who volunteered for an early telaprevir study and says he's been hepatitis-free for three years.

The new drugs do add side effects to the flulike symptoms and other complaints of existing treatment. Telaprevir's main risk is a rash that is sometimes severe, and boceprevir's is anemia.

"The future looks very bright beyond telaprevir and boceprevir," notes Dr. Fred Poordad of Cedars-Sinai Medical Center in Los Angeles, who has studied both drugs and consults for several companies. He points to additional drugs in earlier-stage testing that promise to target more types of hepatitis C and perhaps eventually allow for pill-only, interferon-free treatment.

Manufacturers haven't said how much the new drugs will add to the price of treatment that already can cost US$30,000, albeit far cheaper than a liver transplant.

A stickier issue: Not everyone suffers serious liver damage and it's hard to predict who will, raising questions about exactly who needs treatment even as drug companies help push for more screening."

That's a concern, acknowledges Jeff Levi of the non-profit Trust for America's Health, also a screening proponent. But when to treat is a doctor-patient decision, and "anyone with chronic infection you do want to be monitoring so you can intervene at the right moment," he adds.
Plus, people with hepatitis C should avoid alcohol and consider other liver-protection steps — and know how to avoid infecting others, he stresses.

Stay tuned: The CDC has begun a study at four hospitals — in New York, Detroit, Houston and Birmingham, Ala. — to see if a one-time hepatitis C test for baby boomers makes sense. Among the boomers, black men in their 50s are at particular risk. CDC plans new guidelines next year.
Meanwhile, "start that conversation" at a routine doctor's visit by asking about hepatitis C risks and testing, Ward advises boomers.

Peregrine Initiates Randomized Phase II Trial of Bavituximab in Chronic Hepatitis C Open-Label Trial Evaluating 12 Weeks of Therapy With Novel Targeted Antibody Bavituximab in Combination With Ribavirin Versus Standard of Care

TUSTIN, CA -- (MARKET WIRE) -- 01/10/11 -- Peregrine Pharmaceuticals, Inc. (NASDAQ: PPHM), a clinical-stage biopharmaceutical company developing first-in-class monoclonal antibodies for the treatment of cancer and viral infections, today announced that it has initiated a randomized Phase II clinical trial in patients with previously untreated genotype-1 hepatitis C virus (HCV) infection. This open-label trial will determine the early virologic response (EVR) rate of patients after 12 weeks of therapy with Peregrine's bavituximab, a phosphatidylserine (PS)-targeting monoclonal antibody with immune-modulating potential, in combination with the antiviral drug ribavirin versus standard of care, pegylated interferon alpha 2a and ribavirin. Peregrine expects to complete enrollment shortly in an ongoing Phase Ib HCV trial and report data by mid-year.

"Our fourth randomized Phase II trial evaluating bavituximab for oncology and viral infections is designed to build on our three prior Phase I HCV trials, which have demonstrated our antibody's acceptable safety and promising signs of antiviral activity," said Steven W. King, president and chief executive officer of Peregrine. "Although there are several targeted antiviral drug candidates in development against HCV, immune stimulation with interferon remains a cornerstone of the standard HCV regimen, but unfortunately causes serious side effects and unacceptable toxicity for many patients. With bavituximab's immune reactivation mechanisms and safety profile to date, we are eager to assess this new combination as a potential alternative to interferon-based regimens for patients infected with HCV."

Bavituximab may address a fundamental "immune evasion" mechanism exploited by many infectious pathogens. A growing body of published data from researchers worldwide shows that bavituximab's PS target, exposed on the surface of cells infected by viruses and protozoan parasites, suppresses the immune system's ability to fight disease. PS-targeting antibodies such as bavituximab bind to PS and block the immunosuppressive signals created by the target, thereby allowing the immune system to mount a robust immune response against the pathogen. In prior HCV clinical trials, bavituximab administered as monotherapy in single and multiple doses demonstrated a positive safety profile with no dose-limiting toxicities or serious adverse events. Bavituximab as a monotherapy also showed promising on therapy antiviral activity of up to 1.5 log viral load reduction.

About the Phase II HCV Trial
In this multicenter Phase II randomized, open-label trial, up to 66 patients with previously untreated genotype-1 chronic HCV infection will be randomly assigned to one of three treatment arms. Patients will receive daily oral ribavirin (1000 mg) with either weekly bavituximab (0.3 mg/kg or 3 mg/kg) or PEG-IFN alpha-2a (180 µg) for up to 12 weeks and will be tested for safety parameters and antiviral activity.

The primary endpoint of the study is the proportion of patients achieving early virologic response (EVR), an early predictor of which patients are likely to clear virus with continued treatment. EVR is defined as a greater than or equal to 2 log reduction in HCV RNA after 12 weeks of treatment. Secondary endpoints include safety, tolerability and HCV viral kinetics. For further information about this trial, please visit www.peregrinetrials.com or http://www.clinicaltrials.gov/ct2/results?term=bavituximab.

About HCV
According to the U.S. Centers for Disease Control and Prevention, an estimated 3.2 million individuals in the United States have chronic hepatitis C virus (HCV) infection. Chronic HCV infection is a serious disease that can result in long-term health problems, including liver damage, liver failure, liver cancer, or death. It is the leading cause of cirrhosis and liver cancer and the most common reason for liver transplant in the United States. Approximately 8,000 to 10,000 people die every year from HCV-related liver disease.

About Bavituximab's Antiviral Approach
Bavituximab is the first in a new class of patented antibody therapeutics that target and bind to phosphatidylserine (PS), a specific phospholipid component of cell membranes. Bavituximab helps reactivate and direct the body's immune system to destroy infected cells and virus particles that exhibit this specific phospholipid on their surface. Since their target is host-derived rather than pathogen-derived, PS-targeting antibodies have the potential for broad-spectrum antiviral activity and are also expected to be much less susceptible to the viral mutations that often lead to drug resistance.

Researchers have found that PS is exposed on the outer membrane of cells infected with HCV, HIV, influenza, herpes viruses, hemorrhagic fever viruses, respiratory syncytial virus, measles as well as other viruses. A growing body of scientific publications, including Nature Medicine and The Journal of Experimental Medicine, has highlighted data on the role of PS and Peregrine's PS-targeting therapies in infectious diseases.

About Peregrine Pharmaceuticals
Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company with a portfolio of innovative monoclonal antibodies in clinical trials for the treatment of cancer and serious viral infections. The company is pursuing multiple clinical programs in cancer and hepatitis C virus infection with its lead product candidate bavituximab and novel brain cancer agent Cotara®. Peregrine also has in-house cGMP manufacturing capabilities through its wholly-owned subsidiary Avid Bioservices, Inc. (www.avidbio.com), which provides development and biomanufacturing services for both Peregrine and outside customers. Additional information about Peregrine can be found at www.peregrineinc.com.

Safe Harbor Statement: Statements in this press release which are not purely historical, including statements regarding Peregrine Pharmaceuticals' intentions, hopes, beliefs, expectations, representations, projections, plans or predictions of the future are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. The forward-looking statements involve risks and uncertainties including, but not limited to, the risk that results from the Phase II HCV trial will not be consistent with results experienced in earlier HCV clinical trials and preclinical studies, the risk that investigators may experience delays in patient enrollment, risk that results may not support registration filings with the U.S. Food and Drug Administration, and the risk that Peregrine may not have or raise adequate financial resources to complete the planned clinical programs. Factors that could cause actual results to differ materially or otherwise adversely impact the company's ability to obtain regulatory approval for its product candidates include, but are not limited to, uncertainties associated with completing preclinical and clinical trials for our technologies; the early stage of product development; the significant costs to develop our products as all of our products are currently in development, preclinical studies or clinical trials; obtaining additional financing to support our operations and the development of our products; obtaining regulatory approval for our technologies; anticipated timing of regulatory filings and the potential success in gaining regulatory approval and complying with governmental regulations applicable to our business. Our business could be affected by a number of other factors, including the risk factors listed from time to time in the company's SEC reports including, but not limited to, the annual report on Form 10-K for the year ended April 30, 2010 and the quarterly report on Form 10-Q for the quarter ended October 31, 2010. The company cautions investors not to place undue reliance on the forward-looking statements contained in this press release. Peregrine Pharmaceuticals, Inc. disclaims any obligation, and does not undertake to update or revise any forward-looking statements in this press release.

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Contact:

Amy Figueroa

Peregrine Pharmaceuticals

(800) 987-8256

info@peregrineinc.com



Source: Peregrine Pharmaceuticals

BMS and Pharmasset to combine BMS-790052 and PSI-7997 HCV DAA candidates for proof-of-concept study...

Pharmasset and BMS initiate first cross-company study combining two QD oral, direct-acting antivirals together both with and without ribavirin.


Bristol-Myers Squibb and Pharmasset are to carry out a proof-of-concept study evaluating their respective investigational drug candidates BMS-790052 and PSI-7977 as oral combination therapy for chronic hepatitis C (HCV). BMS-790052 is BMS’ NS5A replication complex inhibitor. Pharmasset’s PSI-7977 is a nucleotide polymerase inhibitor.

The proof-of-concept study will evaluate whether the once-daily oral therapy with the drug duo, either with or without concomitant ribavirin therapy, can lead to a sustained viral response 24 weeks post-treatment in patients chronically infected with HCV genotypes 1, 2, and 3. The trial is expected to start during the first half of 2011. The partners claim it will be the first cross-company study combining two oral, direct-acting antivirals.

At the start of November BMS reported positive data from an open-label Phase IIa trial evaluating a combination of BMS-790052 with its own NS3 protease inhibitor BMS-650032 in HCV genotype 1 patients who had previously not responded to standard HCV therapy with interferon and ribavirin (pegIFNα/RBV). The study showed that when given alongside pegIFNα/RBV treatment, a combination of BMS-790052/BMS-650032 led to 9/10 patients achieving complete early virologic response (cEVR, defined as undetectable viral load) by week 12.

Pharmasset’s PSI-7977, meanwhile, is a uracil nucleotide analog inhibitor of the NS5B polymerase. The drug is currently undergoing Phase IIb evaluation. In December 2010 Pharmasset announced the start of a Phase IIb interferon-sparing trial evaluating PSI-7977 in combination with ribavirin (RBV), and with either 0, 4, 8, or 12 weeks of pegIFNα, as therapy in treatment-naïve patients infected with HCV genotype 2 or 3.

Just last week the firm separately reported positive data from another Phase IIb study, which showed that combining PSI-7977 with pegIFNα/RBV therapy resulted in potent viral suppression in patients with HCV genotype 2 or 3, over 12 weeks. Pharmasset says it plans to initiate a separate Phase IIb combination study during 2011, to evaluate PSI-7977 in combination with pegIFNα/RBV over 24 weeks. PSI-7977 is separately being evaluated in a 14-day Phase I trial as combination therapy with the firm’s guanine nucleotide analog, PSI-938.

Drug Rash with Eosinophilia and Systemic Symptoms due to Telaprevir.

Interesting case study on Telaprevir rash on BioPortfolio.com, originally published in the journal 'Dermatology' last year.


Summary

We report a case of drug rash with eosinophilia and systemic symptoms (DRESS) due to telaprevir (VX-950), a specific inhibitor of the hepatitis C virus (HCV) serine protease. A 57-year-old woman with chronic hepatitis C was included in a phase 2 rollover study of VX-950. She received VX-950 in combination with pegylated interferon alfa-2a and ribavirin. Six weeks later, she developed a generalized pruritic maculopapular exanthema with malaise, fever, dyspnoea and lymph node swelling. She had an eosinophilia (up to 2.7 x 109 cells/l), large activated lymphocytes and increased concentrations of aminotransferases. Histological examination of a cutaneous biopsy was consistent with a drug rash reaction. The HCV treatment was stopped, and she was treated with topical and oral steroids. Cutaneous and systemic symptoms disappeared within 1 month. Telaprevir was considered the culprit drug. We report to our knowledge the first case of DRESS syndrome due to telaprevir. The safety data of telaprevir is derived mainly from the PROVE1, PROVE2 and PROVE3 studies. They showed a high frequency of cutaneous side effects reported under the imprecise terms of pruritus and rash, leading to an increased rate of treatment discontinuation. Telaprevir, due to its efficacy, is probably on the way to obtaining regulatory approval in the near future. It is therefore important to be aware of the high incidence of cutaneous side effects and better describe them. Our observation suggests that potentially severe hypersensitivity reactions may belong to the spectrum of rashes induced by this drug.
Affiliation

Department of Dermatology, University Hospital of Nice, Nice, France.
Journal Details

Name: Dermatology (Basel, Switzerland)
ISSN: 1421-9832
Pages:
Original article here: http://www.bioportfolio.com/resources/pmarticle/63601/Drug-Rash-With-Eosinophilia-And-Systemic-Symptoms-Due-To-Telaprevir.html

Inhibitex bullish on it's Phase 1b safety and antiviral data for INX-189....

Phase 1b data for nuc INX-189. Monotherapy doses with 25 mg are good for a log drop in VL after 7 days, minimal adverse events and QD dosing. Inhibitex is gearing up for more early phase monotherapy trials, as well as trials with ribavirin. Nothing mentioned about peg-interferon... interesting.


Released: 01/09/11 06:00 PM EST

Inhibitex, Inc. (Nasdaq: INHX) today reported positive preliminary interim safety and antiviral data from the first two monotherapy cohorts of its ongoing Phase 1b clinical trial of INX-189, an oral NS5b nucleotide inhibitor being developed to treat chronic infections caused by hepatitis C virus (HCV).

The trial, which is being conducted under an IND in the United States, is a double-blind, placebo-controlled, dose escalation study designed to evaluate the safety, tolerability, pharmacokinetics and antiviral activity of INX-189, administered orally once-daily for seven days, for the treatment of HCV genotype 1 treatment naïve patients. Each treatment cohort in the study is comprised of 10 patients, eight that receive INX-189 and two that receive placebo. In addition to the 9 mg and 25 mg dose cohorts, the Company plans to enroll up to three more INX-189 monotherapy cohorts in the study, as well as two cohorts that will receive different doses of INX-189 once daily for seven days in combination with ribavirin.

INX-189, dosed once-daily at 9mg and 25mg for seven days, demonstrated potent antiviral activity with a mean HCV RNA reduction from baseline levels of -0.71 and -1.03 log10 IU/mL, respectively. The mean HCV RNA decline from baseline levels observed in patients that received placebo was -0.06 log10 IU/mL. The HCV RNA declines from baseline were statistically significant from placebo, with p-values of 0.0156 and 0.0006 in the 9 mg and 25 mg cohorts, respectively. In addition to the mean reductions in viral load, clinically meaningful decreases in alanine transaminase (ALT) levels were observed for patients receiving INX-189 at both dose levels and no patients experienced viral breakthrough.


Preliminary assessments of the data available from the first two cohorts in the Phase 1b study indicate that INX-189 was well tolerated. There were no serious adverse events reported, no discontinuations due to an adverse event, and no adverse events related to changes in clinical laboratory evaluations. All reported adverse events were mild or moderate and were not dose dependent. In addition, the pharmacokinetics of the 9mg and 25mg doses in HCV-infected patients were comparable to those observed in healthy volunteers, and continue to support the evaluation of INX-189 as a once-daily therapy.

“We are pleased with the interim results of the trial to-date and the rapid and potent antiviral activity demonstrated at these low doses of INX-189,” commented Joseph M. Patti, Ph.D., Inhibitex’s CSO and Senior Vice-President of Research. “We look forward to completing the remaining monotherapy cohorts and evaluating the potential antiviral synergies of INX-189 in combination with ribavirin in this ongoing study, and anticipate reporting additional safety, antiviral and pharmacokinetic data from the study upon its completion later this quarter.”

About HCV and INX-189

Hepatitis C is a disease of the liver caused by HCV. It is estimated that over 4 million Americans and 170 million individuals worldwide are infected with HCV, the majority of which represent chronic infections that can cause liver disease, cirrhosis and cancer, and is the leading cause of liver transplants in the United States.

Inhibitex is developing a series of proprietary nucleotide inhibitors that target the RNA-dependent RNA polymerase (NS5b) of HCV. INX-189 is a protide of a 2’-C-methylguanosine analogue. The Company believes that preclinical and clinical studies of INX-189 completed to-date support its potential as a potent, once-daily oral therapy amenable to combination with other antivirals for the treatment of patients with all known genotypes of HCV.

In a Phase 1a study, 42 healthy volunteers received either a single oral dose of INX-189, ranging from 3 mg to 100 mg, or placebo. The Company plans to present detailed results from this trial during a future scientific meeting. Preliminary data from the trial demonstrated the following:

* INX-189 was well tolerated at all dose levels;
* No drug-related serious adverse events;
* No dose-related trends in frequency or type of adverse events; adverse events occurring in more than one subject were headache, nasal congestion, ecchymosis, and presyncope;
* No grade II or higher laboratory abnormality adverse events; and
* Pharmacokinetic data supported INX-189’s potential for once-daily dosing.

Update on Pharmasset's PSI-7977 and PSI-938....

UPDATE 1-Pharmasset says HCV drugs show promise
7:48am EST

* PSI-7977 shows rapid viral suppression

* PSI-938 found to be well tolerated

Jan 6 (Reuters) - Pharmasset Inc (VRUS.O: Quote, Profile, Research, Stock Buzz) said interim analyses of clinical studies of its two drugs for chronic hepatitis C showed promise.

A mid-stage study of the drug, codenamed PSI-7977, showed rapid viral suppression with all patients remaining below limit of detection at the end of treatment. No serious adverse events were reported.

The drug was granted "fast track" designation in August. Fast-track status is designed to expedite the review of drugs to treat serious diseases and fill unmet medical needs. [id:nSGE67B0JZ]

The company said it expects to start a 24-week mid-stage study of the drug in the second quarter of 2011.

An early-stage study of the drug, codenamed PSI-938, as a monotherapy was found to be safe and well-tolerated, Pharmasset said.

The Princeton, New Jersey-based company's shares, which have risen 50 percent in the last three months, closed at $46.59 on Wednesday on Nasdaq. (Reporting by Shravya Jain in Bangalore; Editing by Sriraj Kalluvila)

Merck gets FDA and EMEA expedited reviews for Boceprevir....

Merck works it's magic once again, potentially securing first mover advantage for Boceprevir. Probably not what Vertex wanted to hear this morning. - Chris


January 06, 2011 08:00 AM Eastern Time
Boceprevir, Merck’s Investigational Oral Hepatitis C Protease Inhibitor, Receives FDA Priority Review and EMA Accelerated Assessment

WHITEHOUSE STATION, N.J.--(BUSINESS WIRE)--Merck, known as MSD outside the United States and Canada, announced today that regulatory applications for boceprevir, Merck's investigational oral hepatitis C virus (HCV) protease inhibitor, were submitted in 2010 and have been accepted for expedited review in both the U.S. and the European Union.

“We are pleased that the FDA and EMA have accepted boceprevir for expedited review. Our goal is to be able to bring forward a new treatment option for patients living with chronic hepatitis C, and we are now closer to that goal”

The U.S. Food and Drug Administration (FDA) granted the New Drug Application (NDA) for boceprevir Priority Review status, a designation given to drugs that offer major advances in treatment, or provide a treatment where no adequate therapy exists. FDA's goal for completing a Priority Review is six months.

Additionally, the European Medicines Agency (EMA) accepted the Marketing Authorization Application (MAA) for boceprevir for accelerated assessment. Accelerated assessment is available for products that respond to unmet medical needs or represent a significant improvement over current treatment options within a major public health interest such as treatment of hepatitis C virus infection.

Data in the NDA and MAA have been provided in support of the proposed use of boceprevir for the treatment of chronic HCV genotype 1 infection, in combination with standard therapy, in adult patients with compensated liver disease who are previously untreated or who have failed previous therapy.

"We are pleased that the FDA and EMA have accepted boceprevir for expedited review. Our goal is to be able to bring forward a new treatment option for patients living with chronic hepatitis C, and we are now closer to that goal,” said Dr. Peter S. Kim, Ph.D., president, Merck Research Laboratories.

Merck's global commitment to advancing hepatitis therapy

Merck is committed to building on its strong legacy in the field of viral hepatitis by continuing to discover, develop and deliver vaccines and medicines to help prevent and treat viral hepatitis. Extensive research efforts are underway to develop differentiated oral therapies that bring innovation to viral hepatitis care.

About Merck

Today's Merck is a global healthcare leader working to help the world be well. Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies, and consumer care and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to healthcare through far-reaching policies, programs and partnerships. For more information, visit www.merck.com.

Forward-Looking Statement

This news release includes “forward-looking statements” within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. Such statements may include, but are not limited to, statements about the benefits of the merger between Merck and Schering-Plough, including future financial and operating results, the combined company’s plans, objectives, expectations and intentions and other statements that are not historical facts. Such statements are based upon the current beliefs and expectations of Merck’s management and are subject to significant risks and uncertainties. Actual results may differ from those set forth in the forward-looking statements.

The following factors, among others, could cause actual results to differ from those set forth in the forward-looking statements: the possibility that the expected synergies from the merger of Merck and Schering-Plough will not be realized, or will not be realized within the expected time period; the impact of pharmaceutical industry regulation and health care legislation; the risk that the businesses will not be integrated successfully; disruption from the merger making it more difficult to maintain business and operational relationships; Merck’s ability to accurately predict future market conditions; dependence on the effectiveness of Merck’s patents and other protections for innovative products; the risk of new and changing regulation and health policies in the U.S. and internationally and the exposure to litigation and/or regulatory actions.

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Anadys Pharmaceuticals intiates Phase IIb study of HCV Polymerase Inhibitor ANA598

Anadys getting it's non-nuc to Phase IIb, that's a pretty big hurdle for this company. If this gets to Phase III, they will have done what many drug developers previously have not. The Phase II graveyard for the DAA's is huge. Interesting that no week 4 (RVR) timepoint is mentioned for this protocol - Chris

SAN DIEGO, January 4, 2011 --Anadys Pharmaceuticals, Inc. (Nasdaq: ANDS) announced today that it has initiated the planned Phase IIb study of ANA598 in combination with pegylated interferon and ribavirin. The protocol for the study has been cleared by the United States Food and Drug Administration (FDA) and Health Canada. Patient screening has begun and patient dosing is expected to commence within the next several weeks. In the study ANA598 will be tested in both treatment-naïve patients and treatment-experienced patients who failed a prior course of therapy with interferon and ribavirin. ANA598 is the Company’s direct-acting antiviral, or DAA, being developed for the treatment of hepatitis C.

“We are excited to initiate this Phase IIb study of ANA598,” said James L. Freddo, M.D., Anadys’ Senior Vice President, Drug Development and Chief Medical Officer. “By establishing safety and efficacy in a greater number of patients, including those who have failed prior HCV treatment, we hope to position ANA598 as a highly attractive HCV agent ready for Phase III development.”
Phase IIb Protocol Design

In the study, approximately 200 chronically infected genotype 1 hepatitis C patients are expected to receive ANA598 200 mg twice a day (bid) in combination with Pegasys® (peginterferon alfa2a) and Copegus® (ribavirin, USP) (a current standard of care, or SOC) with a loading dose of 800 mg bid on day 1, while approximately 66 patients are to receive placebo and SOC. Enrollment is expected to include approximately equal numbers of treatment-naïve patients and patients who have failed a prior course of SOC, including difficult to treat prior null-responders. The primary endpoint of the study is Sustained Virological Response 24 weeks after patients conclude all treatment, known as SVR24. Anadys is conducting the study at sites within and outside the United States.
Naïve Arm

Approximately 100 treatment-naïve HCV patients are expected to receive ANA598 in combination with SOC and 33 treatment-naïve HCV patients are to receive placebo plus SOC. Treatment duration for naïve patients will be response-guided; patients who achieve undetectable levels of virus at Week 8 and maintain undetectable levels of virus will be scheduled to conclude all treatment at Week 28. For naïve patients with detectable virus at Week 8 dosing with ANA598, or placebo, and SOC is planned to continue through Week 48. The Company expects to receive Week 8 antiviral response data by the end of the second quarter of 2011, Week 12 antiviral response data in the third quarter of 2011 and Week 24 antiviral response data in the fourth quarter of 2011.

Treatment-Experienced Arm, Including Prior Null Responders

Approximately 80 patients who were partial responders during, or relapsers after, a prior course of therapy with SOC alone are expected to receive ANA598 in combination with SOC, and 33 corresponding patients are to receive placebo plus SOC. Additionally, approximately 28 prior null responder patients are to receive ANA598 in combination with SOC. All treatment-experienced patients who receive ANA598 are scheduled to receive triple combination therapy for 48 weeks. For the treatment-experienced patients, the Company expects to receive Week 12 antiviral response data in the third quarter of 2011 and Week 24 antiviral response data in the fourth quarter of 2011.

Can elevated IP-10 become a reliable predictive biomarker for response to Pegylated Interferon & Ribavirin?

Move over LabCorp!! Press release regarding a potential diagnostic test to predict response to pegylated interferon/ribavirin from Inserm and Institut Pasteur in collaboration with the Rules Based Medicine, Inc from the US.

Scientists at Inserm and Institut Pasteur have performed biomarker discovery on patients being treated for chronic hepatitis C infection. Their work, published in The Journal of Clinical Investigation, demonstrates that the plasma levels of the protein IP-10 predict, prior to treatment initiation, the efficacy of treatment with pegylated-interferon and ribavirin. Based on these results, the scientists have developed a prognostic test. Commercialization is anticipated in 2011, and will help inform physicians of the chances that patients will respond to standard treatment or if instead they will require new therapeutic cocktails (e.g., inclusion of protease inhibitors).

Importantly, hepatitis C is the leading cause of primary liver cancer (hepatocellular carcinoma) and it remains an important cause of liver failure due to fibrosis and cirrhosis. This infectious disease represents a major public health problem, with greater than 170 million cases worldwide. The World Health Organization estimates 3 to 4 million new cases per year and considers the virus a " viral time bomb" due to the long term sequella of infection.

Currently, there is no approved vaccine available and approximately 80% of individuals infected by the virus develop chronic disease, a risk factor for cirrhosis, liver failure, liver cancer as well as other medical complications (e.g., diabetes).

For the past ten years, treatment has been based on the use of type I interferon given in combination with the anti-viral ribavirin. While effective, it results in a cure for only 50% of patients. Moreover, treatment is long (24 – 48 weeks), and it results in severe side effects (e.g., depression, anemia).

It is in this context that the Inserm and Institut Pasteur sponsored research lab of Dr. Matthew Albert, in close collaboration with the Liver Disease Unit headed by Prof. Stanislas Pol, evaluated plasma biomarkers to define predictors for patients' response to treatment.

With the help of the Centre for Human Immunology at Institut Pasteur, the investigators involved have performed a prospective study. They identified the protein IP-10 as a prognostic biomarker – elevated in those patients for whom treatment was ineffective. This observation was paradoxical as IP-10 is considered a pro-inflammatory molecule, which should have facilitated migration of activated T cells to the liver, the exact cell types responsible for viral immunity. In fact, what was discovered is that the IP-10 had been catabolized and it was a truncated form present in the HCV patients. Strikingly, the short form of IP-10 is an antagonist and inhibits T cell recruitment. Thus, it is suggested that the antagonist form of IP-10 is responsible for the failure to respond to treatment in the 50% of patients who do not benefit from pegylated-interferon / ribavirin treatment.

The investigators worked in close collaboration with an American company, Rules Based Medicine, Inc., who will develop a diagnostic test to distinguish the different forms of IP-10 as a simple blood test. This test will be a significant step towards the improved management of patients with HCV as well as other chronic inflammatory diseases.

###

This scientific work was conducted under the direction of Matthew L. Albert, MD PhD, Mixed Institut Pasteur / Inserm Research Unit; and Stanislas Pol, MD PhD, Univerisity of Paris, Descartes and Institut Cochin. Financial support was provided by the ANRS and promotion of the study was taken by Inserm Medical.

To know more:

Source

Evidence for chemokine antagonisms in human infected chronically with Hepatitis C Virus.
Armanda Casrouge, Jérémie Decalf, Mina Ahloulay, Cyril Lababidi, Hala Mansour, Anaïs Vallet-Pichard, Vincent Mallet, Estelle Mottez, James Mapes, Arnaud Fontanet, Stanislas Pol and Matthew L. Albert.

Journal of Clinical Investigation.

and the related news article

Chemokine antagonism in chronic hepatitis C virus infection.
Edgar D. Charles and Lynn B. Dustin

Journal of Clinical Investigation.

Contact information

Matthew Albert
Unité mixte Institut Pasteur / Inserm
Email : albertm@pasteur.fr
Tel : +33 6 7001 0396

Stanislas Pol
Unité 1016 « Institut Cochin »
Service Hépatologie, Hôpital Cochin
Email : stanislas.pol@cch.aphp.fr

A mutation in Genotype 3a patients may explain lack of response to standard of care treatment...

(Study in 6 genotype 3a patients from the Virology Journal which probably wouldn't garner much interest other than the fact that the authors suggests that a mutation involving the substitution of glutamine (Q) with Leucine (L) in the one of the 3 breakthrough responders in the study made the area in question identical to the same region in HCV genotype 1a - maybe one clue as to why treatment in G3 patients is tougher than G2. Because of the mutation, the HCV virus may have the same ability to evade the immune system that we see in genotype 1a patients - Chris)

Hepatitis C is a major health problem affecting more than 200 million individuals in the world. Current treatment regimen consisting of interferon alpha and ribavirin does not always succeed in eliminating the virus completely from patient's body.

One of the mechanisms by which virus evades the antiviral effect of interferon alpha involves protein kinase (PKR) eukaryotic initiation factor 2 alpha (eIF2a) phosphorylation homology domain (PePHD). This domain in genotype 1 strains is reportedly homologous to PKR and its target eIF2a.

By binding to PKR, PePHD inhibits its activity and therefore cause virus to evade antiviral activity of interferon (IFN). Many studies have correlated substitutions in this domain to the treatment response and lead to inconclusive results.

Some studies suggested that substitutions favor response while others emphasized that no correlation exists. In the present study we therefore compared sequences of PePHD domain of thirty one variants of six hepatitis C virus patients of genotype 3.

Three of our HCV 3a infected patients showed rapid virological response to interferon alpha and ribavirin combination therapy whereas the remaining three had breakthrough to the same combination therapy. It is found that PePHD domain is not entirely conserved and has substitutions in some isolates irrespective of the treatment response.

However substitution of glutamine (Q) with Leucine (L) in one of the breakthrough responders made it more identical to HCV genotype 1a. These substitutions in the breakthrough responders also tended to increase average hydrophilic activity thus making binding of PePHD to PKR and inhibition of PKR more favorable.

Author: Samia AfzalMuhammad IdreesMadiha AkranZunaira AwanBushra KhubaibMahwish AftabZareen FatimaSadaf BadarAbrar Hussain
Credits/Source: Virology Journal 2010, 7:377