July 29, 2010

ANA598 Demonstrates SVR12 in 100% of First Group of HCV Patients Randomized to Stop All Treatment at Week 24

Benefit of ANA598 Post Therapy with IFN/RBV Persists in 6 of 6 Patients

Company to Review Data During Q2 Financial Results Call at 8:30 AM EDT Today

SAN DIEGO, July 29 /PRNewswire-FirstCall/ -- Anadys Pharmaceuticals, Inc. (Nasdaq: ANDS) today announced that six of six patients (100%) in the ANA598 200 mg twice daily (bid) arm who were randomized to stop all treatment at Week 24 in an ongoing Phase II trial maintained undetectable levels of virus 12 weeks after stopping treatment, referred to as Sustained Virological Response 12, or SVR12.

The Company also reported that all available patients from the ANA598 200 mg arm who were previously reported to have undetectable levels of virus at Week 24 and continued on pegylated interferon and ribavirin (current standard of care, or SOC) also maintained undetectable levels of virus at Week 36. In addition, all patients from the ANA598 400 mg arm who were previously reported to have undetectable levels of virus at Week 12 and continued on SOC maintained undetectable levels of virus at Week 24. ANA598, Anadys' direct-acting antiviral or DAA, is being developed to treat hepatitis C and is in an ongoing Phase II trial in combination with pegylated interferon and ribavirin.

"The SVR12 data reported today for ANA598 are highly encouraging," said Steve Worland, Ph.D., President and CEO of Anadys. "These data illustrate the potential for HCV patients to be successfully treated with shortened courses of treatment, reflecting the continuing benefit of ANA598 post-therapy. We believe these data, coupled with the excellent barrier to resistance demonstrated in this trial as well as the favorable safety and tolerability, confirm ANA598's position as one of the most attractive agents in Phase II HCV development today."

The six patients who stopped all treatment at Week 24 were part of an investigation of response-guided treatment duration for ANA598 in which patients who had achieved undetectable levels of virus (<15 IU/mL) at Weeks 4 and 12 were randomized 1:1 to stop all treatment at Week 24 or Week 48. In addition to the six patients who stopped treatment at Week 24, six patients in the 200 mg bid arm are continuing to receive SOC alone through Week 48 for comparison purposes. Additionally, 14 patients from the ANA598 400 mg bid arm and 4 patients from the control arm (receiving placebo plus SOC) met the stopping criteria and have been randomized to stop all treatment at Week 24 or 48. The initial post-treatment results from these latter arms are expected later this year for those patients who stopped therapy at Week 24.

Conference Call Webcast and Slides

Anadys will hold a conference call and webcast today, Thursday, July 29, 2010 at 8:30 a.m. Eastern Daylight Time to discuss the post-treatment results from the ongoing Phase II combination study and Anadys' second quarter 2010 financial results A live webcast of the call, including accompanying slides, will be available online at www.anadyspharma.com. A telephone replay with slides will also be available approximately one hour after completion of the call. To access the telephone replay, dial 888-286-8010 (domestic) or 617-801-6888 (international), passcode 28631163. The webcast and telephone replay will be available through August 12, 2010.

Phase II Combination Study

In the ongoing Phase II study, approximately 90 treatment-naive genotype 1 HCV patients have received ANA598 or placebo in combination with Pegasys® (peginterferon alfa-2a) and Copegus® (ribavirin, USP) for 12 weeks at dose levels of 200 mg bid or 400 mg bid, each with a loading dose of 800 mg bid on day one. After week 12, patients are to continue receiving SOC. Patients who achieved undetectable levels of virus at weeks 4 and 12 were randomized to stop all treatment at week 24 or 48. The primary endpoint of the study is the proportion of patients who achieve undetectable levels of virus at week 12 (defined as complete Early Virological Response, or cEVR). Additional endpoints include safety and tolerability as well as the proportion of patients with undetectable levels of virus at week 4 (defined as Rapid Virological Response, or RVR). Patients will be followed for 24 weeks after stopping therapy to determine the rate of Sustained Virological Response, or SVR. Approximately 90 patients have been enrolled in this study – with approximately 30 patients receiving ANA598 plus SOC at each dose level and 30 patients receiving placebo plus SOC. The study is being managed by the Duke Clinical Research Institute (DCRI) and is being conducted at a number of clinical sites in the United States.

About ANA598

ANA598, a direct-acting antiviral or DAA, is a non-nucleoside inhibitor of the HCV RNA polymerase and is wholly owned by Anadys. In an ongoing Phase II study in which HCV patients received ANA598 at 200 mg bid or 400 mg bid in combination with interferon and ribavirin for twelve weeks, both dose levels showed comparable cEVR rates of 73-75% and a favorable safety profile. In a previous Phase I study, ANA598 demonstrated potent antiviral activity, including median end-of-treatment declines in viral load ranging from 2.4 to 2.9 log10 in a three day monotherapy study in treatment-naïve genotype 1 patients. ANA598 has also demonstrated a very favorable resistance profile.

Anadys has completed two long-term chronic toxicology studies of ANA598 (26 weeks duration in rats and 39 weeks duration in monkeys). The No Observed Adverse Effect Level, or NOAEL, is 1000 mg/kg, the highest dose tested, in both the rat and monkey. The completed toxicology studies support the ongoing Phase II clinical study as well as future clinical studies of longer duration.

Anadys has presented in vitro data supporting the use of ANA598 in combination with interferon-alpha as well as with other anti-HCV agents currently in development that act through diverse mechanisms. In particular, data has shown that ANA598 is synergistic in vitro with interferon-alpha as well as representative HCV protease inhibitors, polymerase inhibitors, NS5A inhibitors and cyclophilin inhibitors. In vitro combination treatment at clinically relevant concentrations of ANA598 with interferon-alpha as well as DAAs from multiple classes results in clearance of HCV RNA from cells rather than selection of resistant isolates. Furthermore, ANA598 retains full activity in vitro against mutations conferring resistance to protease inhibitors, nucleoside polymerase inhibitors and non-nucleoside polymerase inhibitors that act at binding sites distinct from that of ANA598, while protease and nucleoside polymerase inhibitors retain full activity in vitro against mutations conferring resistance to ANA598.

ANA598 has received Fast Track Status from the FDA for the treatment of chronic 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 (i) ANA598's initial SVR12 profile based on the results from the six patients in this first group; (ii) the potential for HCV patients to be successfully treated with shortened courses of treatment, reflecting the continuing benefit of ANA598 post-therapy; (iii) the belief that ANA598 is one of the most attractive agents in Phase II HCV development today; (iv) the expected timing for post-treatment results from the other dose groups; and (v) the ability for patients to achieve an SVR in the Phase II combination 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 or will continue to have favorable results as the Phase II trial progresses. 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 preclinical 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-K for the year ended December 31, 2009, Form 10-Q for the quarter ended March 31, 2010 and Form 8-K filed on May 26, 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.

Pegasys® and Copegus® are registered trademarks of Hoffman-La Roche Inc.

SOURCE Anadys Pharmaceuticals, Inc.



On the street, you can see the harm caused by drug laws

By David Bratzer, Citizen Special July 29, 2010

Like many other police officers, I have witnessed the tragedy of the HIV epidemic first hand. It is one thing to read the statistics demonstrating the connection between illicit drug use and HIV; it is another matter entirely to patrol the streets, day in and day out, repeatedly arresting men and women infected with the HIV virus.

Our country has one of the finest health-care systems in the world, but our laws surrounding drug use result in unnecessary disease and death.

In this context, the recent announcement of the Vienna Declaration has bolstered my conviction that drug prohibition is a national policy failure.

The document, inspired by an international team of leading health scientists and academic physicians, is the official declaration of this month's International AIDS Conference in Vienna. It presents an important scientific fact that I see reflected in my work every day: "The criminalization of illicit drug users is fuelling the HIV epidemic and has resulted in overwhelmingly negative health and social consequences."

The declaration calls for a "full policy reorientation." This should not be misconstrued as an endorsement of drug use. It is simply a recognition that drug law enforcement is not an effective deterrent, citing studies showing "there is no evidence that increasing the ferocity of law enforcement meaningfully reduces the prevalence of drug use."

It is also a recognition that drug law enforcement is contributing directly to the HIV epidemic. In most parts of the world, approximately one in three HIV infections can be traced back to intravenous drug use. Toronto, Ottawa, Surrey, Winnipeg and other Canadian cities are not immune.

Drug prohibition increases the rate of HIV infections. When illegal drugs are sold through the black market, the only concern is making money. There is no financial incentive for traffickers to provide drug education, counselling or harm reduction services such as sterile needles.

In addition, in parts of Canada it is common for an injection drug user to be arrested for a minor drug charge and end up with a court-imposed condition to abstain from possessing drug paraphernalia. Addicts are then forced to choose whether to carry sterile needles and risk a new criminal charge, or to share a needle with another addict who may already have a blood-borne disease.

The Vienna Declaration is particularly important within Canada. Bill S-10 is before Parliament. It is the federal government's third attempt in as many years to create mandatory minimum sentences for certain drug offences.

The wording of this legislation virtually guarantees that street-level drug addicts will find themselves going to jail for lengthy prison terms. This will do nothing but channel limited tax dollars away from health and education and into costly incarceration policies which will turn petty drug users into hardened criminals.

HIV prevention efforts will be hampered if this bill passes. The HIV infection rates in federal prisons are similar to some African countries, according to the statistics provided by the Correctional Service of Canada. So, for many of these addicts, part of their sentence will include a substantial risk of contracting HIV or Hepatitis C.

Of course, the Vienna Declaration is not the first time a major initiative has been announced to coincide with the biannual International AIDS Conference. Ten years ago, the Durban Declaration stated a basic scientific truth: that HIV is the cause of AIDS. More than 5,000 scientists and medical doctors signed the document in an effort to confront AIDS denialism.

The main critic of the Durban Declaration was Thabo Mbeki, who was president of South Africa at the time. He believed, mistakenly, that there was a causal link between poverty and AIDS. In fact it is HIV that causes AIDS. His denials, rooted in ignorance and willful blindness, have cost many lives in South Africa.

Given this history, it will be interesting to see who opposes the Vienna Declaration. Police lobby groups have traditionally been the most vocal critics of drug policy reform. In this instance, however, they should choose their responses carefully. At stake is the very credibility of these organizations. They risk being remembered in the same light as President Mbeki, for it is clear that the new AIDS denialism is the failure to acknowledge the realities of HIV transmission.

The Vienna Declaration will play a significant role in HIV policy, and I am proud to have signed the document online at viennadeclaration.com.

I can only hope that my colleagues in law enforcement will be inspired to do the same.

David Bratzer is a member of the board of directors for Law Enforcement Against Prohibition and a police officer in British Columbia. The opinions expressed in this column do not represent the views of his employer.

© Copyright (c) The Ottawa Citizen


RNA Offers a Safer Way to Reprogram Cells

MIT researchers used RNA to induce these fibroblast cells to express four genes necessary to reprogram cells to an immature state. (Credit: Yanik Laboratory, MIT)

ScienceDaily (July 29, 2010) — In recent years, scientists have shown that they can reprogram human skin cells to an immature state that allows the cells to become any type of cell. This ability, known as pluripotency, holds the promise of treating diseases such as diabetes and Parkinson's disease by transforming the patients' own cells into replacements for the nonfunctioning tissue.

However, the techniques now used to transform cells pose some serious safety hazards. To deliver the genes necessary to reprogram cells to a pluripotent state, scientists use viruses carrying DNA, which then becomes integrated into the cell's own DNA. But this so-called DNA-based reprogramming carries the risk of disrupting the cell's genome and leading it to become cancerous.

Now, for the first time, MIT researchers have shown that they can deliver those same reprogramming genes using RNA, the genetic material that normally ferries instructions from DNA to the cell's protein-making machinery. This method could prove much safer than DNA-based reprogramming, say the researchers, Associate Professor of Electrical and Biological Engineering Mehmet Fatih Yanik and electrical engineering graduate student Matthew Angel.

Yanik and Angel describe the method, also the subject of Angel's master's thesis, in the July 23 issue of the journal PLoS ONE.

However, the researchers say they cannot yet claim to have reprogrammed the cells into a pluripotent state. To prove that, they would need to grow the cells in the lab for a longer period of time and study their ability to develop into other cell types -- a process now underway in their lab. Their key achievement is demonstrating that the genes necessary for reprogramming can be delivered with RNA.

"Before this, nobody had a way to transfect cells multiple times with protein-encoding RNA," says Yanik. (Transfection is the process of introducing DNA or RNA into a cell without using viruses to deliver them.)

In 2006, researchers at Kyoto University showed they could reprogram mouse skin cells into a pluripotent, embryonic-like state with just four genes. More recently, other scientists have achieved the same result in human cells by delivering the proteins encoded by those genes directly into mature cells, but that process is more expensive, inefficient and time-consuming than reprogramming with DNA.

Yanik and Angel decided to pursue a new alternative by transfecting cells with messenger RNA (mRNA), a short-lived molecule that carries genetic instructions copied from DNA.

However, they found that RNA transfection poses a significant challenge: When added to mature human skin cells, mRNA provokes an immune response meant to defend against viruses made of RNA. Repeated exposure to long strands of RNA leads cells to undergo cell suicide, sacrificing themselves to help prevent the rest of the body from being infected.

Yanik and Angel knew that some RNA viruses, including hepatitis C, can successfully suppress that defensive response. After reviewing studies of hepatitis C's evasive mechanisms, they did experiments showing they could shut off the response by delivering short interfering RNA (siRNA) that blocks production of several proteins key to the response.

Once the defense mechanism is shut off, mRNA carrying the genes for cell reprogramming can be safely delivered. The researchers showed that they could induce cells to produce the reprogramming proteins for more than a week, by delivering siRNA and mRNA every other day.

Also See: RNA offers a safer way to reprogram cells

Greater Risk Of Diabetes Found In Hepatitis C Patients

By Steven Marsh • Jul 28th, 2010 • Category: Blood Sugar, Health News, Health Resources News

Patients who have been diagnosed with hepatitis C may be more susceptible to developing type 2 diabetes, according to a study published in the journal Gastroenterology.

A blood-born disease, hepatitis C spreads through unprotected sexual intercourse or the use of injection drugs and causes liver damage. If people don’t receive treatments for this disease, they can suffer from liver cancer or failure of the organ, resulting in death.

During the study, a team of investigators monitored a total of 29 patients with hepatitis C who showed signs of insulin resistance, a symptom of diabetes.

The results of the trial showed that 15 of the participants experienced insulin complications in their muscle tissue compared to the liver. The inability to properly absorb the sugar created high levels of the nutrient in the blood, which could lead to developing diabetes.

"At this stage, it is helpful for people with hepatitis C to understand insulin resistance and what it can mean for them," said Don Chisholm, co-author of the study. He added that "if they have relatives with type 2 diabetes, they will be genetically prone to developing it themselves and so would be advised to manage their diets very carefully and take plenty of exercise – to slow onset."

As of 2007, an estimated 17,000 new cases of hepatitis C are diagnosed in the U.S. each year, according to the Centers for Disease Control and Prevention.


Bid To Aid Transplant Cancer Patients

Article Date: 29 Jul 2010 - 1:00 PDT

Organ transplant patients who develop cancer may be helped by a treatment that uses blood cells to attack their tumour.

University of Edinburgh researchers have generated a bank of white blood cells from healthy blood donors to treat patients with a blood cancer called post transplant lymphoproliferative disease (PTLD).

The study found that patients treated with these blood cells - called 'killer' T cells - remained free from the cancer for up to nine years following treatment.

PTLD is associated with Epstein-Barr virus (EBV), a herpes virus that is carried by more than 90 per cent of the population and better known for causing glandular fever.

In most individuals the virus does not cause any illness but it can cause tumours in transplant patients.

This is because their immune systems are heavily suppressed to prevent rejection of the transplanted organ.

Up to 10 per cent of transplant patients may develop the cancer in the first few years following transplant and around 50 per cent of those will die even with standard treatment.

T cells are a type of white blood cell that patrol the body identifying and killing virus infected cells.

A team at the University of Edinburgh's Centre for Infectious Diseases grew T cells in the laboratory and gave them to PTLD patients for one month.

The T cells were programmed to find and kill the virus-infected tumour cells to reduce or eradicate the tumour.

A total of 33 PTLD patients who had not responded to standard treatments were treated in a Cancer Research UK-funded trial.

Around half the treated patients showed a good response after six months.

This latest study shows that 90 per cent of those who responded initially have remained cancer free for between four and nine years.

The long term survival rate was significantly better in the six month responder group compared to the six month non-responder group.

"Our results are very encouraging and show that not only are our cells effective in the short term but that they can also induce a long term remission of PTLD in patients with more unmanageable disease."

said Dr Tanzina Haque, Lead researcher, now of Royal Free Hospital, UCL Medical School.

The Edinburgh researchers in conjunction with the Scottish National Blood Transfusion Service have obtained translational funding from the Wellcome Trust to make a new bank of 'killer' T cells that will become available for use on a not-for-profit basis in the next few years.

The research is published in the journal Transplantation.

University of Edinburgh


Hepatitis C retreatment offers hope if initial one fails

by paige varner pvarner@post-dispatch.com 314-340-8018

Posted: Thursday, July 29, 2010 12:00 am
For the 40 percent to 50 percent of patients who aren't cured of hepatitis C after their initial treatment, Dr. Bruce R. Bacon of St. Louis University and his team of researchers have increased the chances of a cure upon re-treatment.
About 11 percent of the 515 people retreated in Bacon's trials were cured using the Food and Drug Administration-approved medication combination, Infergen with an antiviral pill.
Of those with milder strains of hepatitis C, about 35 percent in the trials were cured.
In the first round of treatment, patients are given weekly shots of an alpha interferon — in larger amounts than that which the body normally makes to fight pathogens — along with the antiviral pill ribavirin.

This combination cures 50 percent to 60 percent of cases, but others can start another round, this time injecting the interferon medicine Infergen daily, along with taking the ribavirin, for up to 48 weeks.

Bacon, who holds the endowed chair in gastroenterology at SLU School of Medicine, and his team published their findings last summer after researching from 2004 to 2006.

For those with the virus who feel the 11 percent cure rate in the second round isn't high enough, Bacon said they will still have hepatitis C if they don't at least try re-treatment.

Another concern about the medicine combination is the side effects, which are similar to the flulike symptoms the virus already causes, such as fatigue, anemia, troubled breathing, irritability.

"But more than the side effects, you don't want to have hepatitis C," Bacon said.

Interferon and ribavirin are the only treatments for hepatitis C, which inflames the liver and after many years can lead to cirrhosis, or liver scarring, in 20 percent to 30 percent of patients.

Those with the virus can prevent cirrhosis development by not drinking excessive amounts of alcohol.

Some won't know they have the virus. Bacon said the flulike symptoms can set in gradually, making them feel sick for decades before they are diagnosed.

Contracting hepatitis C requires a blood-to-blood transmission, and Bacon said most cases have a history of one of three things:

• A blood transfusion before 1992.

• Sharing needles or illicit drugs — "even teenagers at a party who did something stupid," Bacon said

• Working in the health care field. Paramedics, physicians and nurses come into contact with blood daily. Just one needle stick could cause hepatitis C.

Acute cases of the virus can clear on their own. Infergen with ribavirin is FDA-approved in chronic cases, or for people who have had the virus for at least six months.

Infergen cannot be taken by anyone under 18 years old or with compensated liver disease due to cirrhosis complications.