Rash scare & potential crowded marketplace keeps ANA598 partnerless...

BioWorld Today - Oct. 18, 2010

Financings Roundup

Having yet to sign a partnership for hepatitis C drug ANA598, Anadys Pharmaceuticals Inc. is pulling in $25 million in a public offering to support an upcoming Phase IIb study of the non-nucleoside polymerase inhibitor.

The San Diego-based firm priced the offering of about 13.9 million shares at $1.80 apiece, marking a 13.5 percent discount to Thursday's closing price.

That discount, plus the added dilution to the company's stock, sent shares (NASDAQ:ANDS) tumbling 33 cents, or 15.9 percent, to close Friday at $1.75.

In May, Anadys raised $12.5 million in a registered direct offering and hired Lazard Freres & Co. LLC to help pursue strategic alternatives such as sale of the company or out-licensing assets.

That includes ANA598, which, despite promising early efficacy data, has been dinged by reports of rash in a Phase Ib trial, followed by a higher-than-expected placebo effect that diminished 12-week virological response data in a Phase II study. (See BioWorld Today, April 24, 2009, and Feb. 26, 2010.)

Add to that the increasing competition in the HCV space, and it's no surprise that prospective partners might be skeptical.

Leerink Swann analyst Howard Liang noted last month that recent Phase III data on HCV protease inhibitors, especially Vertex Pharmaceuticals Inc.'s telaprevir "set a high efficacy bar" while early data for NS5A inhibitor BMS-790052 from Bristol-Myers Squibb Co. and nucleoside polymerase inhibitors for Roche AG (RG7128) and Pharmasset Inc. (PSI-7977) also have been impressive.

"In comparison, ANA598's early data do not look compelling," Liang wrote in a Sept. 27 research report.

Anadys is hoping that further Phase II data and results from the Phase IIb study slated to start early next year might prove tempting enough to snag a partner to help with the costly Phase III program.

The ongoing Phase II study is testing ANA598 in combination with the standard-of-care regimen pegylated interferon and ribavirin in treatment-naive HCV patients with genotype 1 disease.

Anadys has data for three of the six patients in the 200-mg twice-daily group, treated for 24 weeks and then had HCV levels measured 24 weeks after all treatment stopped. All three of those patients achieved sustained viral response.

The planned 48-week Phase IIb trial will test ANA598, again in combination with pegylated interferon and ribavirin, in about 200 patients, including both treatment-naive and treatment-experienced subjects.

Anadys is working to finalize the design with the FDA.

Elsewhere in its pipeline, the company has ANA773, an HCV drug designed to induce endogenous interferon that acts via the Toll-like receptor 7 pathway.

Work on that program was suspended in 2009 to concentrate resources on ANA598, but data from a monotherapy trial, plus recent developments suggesting that interferon-based treatment might continue to have a place in the HCV landscape, prompted the firm to restart ANA773. A 28-day combination study of the drug plus ribavirin is expected to begin dosing in the second quarter of 2011 . (See BioWorld Today, June 5, 2009.)

Proceeds from the latest financing, which will add to the $22. 1 million Anadys had in the bank as of June 30, also will be used for general corporate purposes, including working capital.

The firm could pull in an additional $3.7 million if underwriter Lazard Capital Markets LLC exercises its full overallotment option of about 2. 1 million shares.

Prior to the offering, Anadys had about 46.2 million shares outstanding.

DGAT-1: A New STAT-C Target?

BioWorld Today - Oct. 14, 2010

Scientists have identified a potential new target in the fight against hepatitis C: diacylglycerol acyl transferase 1, or DGAT-1, an enzyme that is involved in fat droplet synthesis in the liver.

In their studies, the authors showed that DGAT1 anchors a key viral protein to the fat droplets, which serve as a sort of staging ground for the assembly of new viral particles in the cell. Inhibiting the enzyme essentially keeps hepatitis C from getting its parts together into new virus particles after the virus has copied its genome.

Other studies had shown that inhibiting fat droplet synthesis prevents hepatitis C virus from assembling. But the inhibition of one specific enzyme "is a very tailored intervention," senior author Melanie Ott told BioWorld Today. "We don't touch . . . the ability of the cell to produce these very important fat droplets . . . we are excited about that." Ott is an investigator at the University of California, San Francisco's Gladstone Institute of Virology and Immunology.

Estimates of just how many people are infected with hepatitis C globally vary widely, from 160 million to almost twice that. But what is clear is that it is a large public health problem. The infection turns chronic in about 80 percent of those who contract it, and can lead to consequences including cirrhosis and liver cancer. And hepatitis C is one of the biggest headaches for HIV-infected individuals, particularly intravenous drug users who often contract both viruses at the same time.

To top it off, roughly half of treated patients respond to the standard treatment and doctors currently have no advance way to tell responders from nonresponders to the harsh regimen. Together, it translates into a need for better therapies.

Ott said her team's work, which was published in the Oct. 10, 2010, online edition of Nature Medicine, was enabled by advances in two separate areas. One is an increasing realization that fat droplets "are an important organelle," not just a cellular storage closet for triglycerides and cholesterol. Fat droplets "used to be thought of as completely uninteresting," she said.

The other is recent advances in the ability to work with the hepatitis C virus itself. "Until 2005, we couldn't really study the virus very well," because it replicated neither in cell culture nor in mice, meaning that studies had to be done in primates.

In their paper, senior author Ott and her team used a DGAT1 inhibitor to treat hepatitis-infected liver cells. They found that such cells did not have any fewer fat droplets than untreated counterparts, but that hepatitis C was able to check into such cells, but not check back out after viral replication.

Further experiments showed that DGAT1 inhibition appears to work by interfering with the hepatitis C virus core protein, which is required for assembling viral particles after replication. That assembly, it turns out, has to happen on the surface of the fat droplets that DGAT1 helps synthesize; without DGAT1 activity, the fat droplets still form, but the viral protein cannot bind to them. The fat droplets "serve as assembly platforms in the cell," Ott said.

DGAT1 has several advantages that could make it a good candidate for therapeutic inhibition.

For one thing, though it appears to be critical for viral assembly, it is not irreplaceable for synthesis of the fat droplets themselves, which have important roles in cellular life. Another enzyme, DGAT2, takes over their synthesis of the fat droplets when DGAT1 is inhibited.

For another, DGAT1 inhibitors are already being tested in the arena of metabolic disorders. Pfizer Inc. completed several Phase I studies of a DGAT1 inhibitor it is developing for the treatment of diabetes earlier this year, and at least one additional trial is ongoing. Other companies also are working on inhibitors, which could obviously also be tested against hepatitis.

Ott's team is also interested in learning more about the biological function of DGAT1. DGAT1 and DGAT2 are "structurally very different, but biochemically very similar," Ott said. Taken together, the available data "point to DGAT1 as something very unique" â?? and from first biological principles, the enzyme's main function is surely not to enable the hepatitis C virus to ravage its owner's livers.

The American Association for the Study of Liver Diseases (AASLD) and the Trust for America's Health (TFAH) issue sobering report on HBV & HCV in America

Washington, DC -- September 27, 2010 -- The American Association for the Study of Liver Diseases (AASLD) and the Trust for America's Health (TFAH) issued a new report today calling for action to be taken to transform how the country deals with viral hepatitis -- to help identify millions of Americans who know they are living with chronic forms of hepatitis B and C and to assure access to treatment for all who need it, to prevent even more Americans from becoming infected.

Main Findings:

An estimated 65 to 75 percent of the five million Americans currently infected with the hepatitis B virus (HBV) or hepatitis C virus (HCV) do not even know they have the virus;

The Institute of Medicine (IOM) estimates that 150,000 Americans could die from liver cancer or end-stage liver disease associated with HBV or HCV in the next decade;

The death rate from HCV is expected to triple in the next 10 to 20 years;

An independent analysis found total medical costs for HCV patients could more than double over the next 20 years -- from $30 to $80 billion per year;

Liver cancer treatment can be more than $62,000 for the first year cost and the first-year cost of a liver transplant can be more than $267,000;

Two-thirds of HCV cases are Baby Boomers -- and if they are left untreated, it could lead to a major increase in upcoming Medicare spending;

One in 10 Asian and Pacific Islander Americans are estimated to have a chronic HBV infection;

An estimated 540,000 to 858,000 African Americans are estimated to have a chronic HCV infection;

Approximately 800 to 1,000 infants in the United States are infected with HBV at birth each year;

At least 100,000 patients have been notified about potential exposure to HBV, HCV, and/or HIV while receiving health care since 1998.

Some highlight recommendations from AASLD and TFAH in the report include:

HBV and HCV screening and HBV vaccination should be the standard of care in the reformed health system. All Americans should be screened for HBV and HCV and all Americans should be vaccinated for HBV;

All pregnant women should be screened for HBV and appropriate health measures should be taken to prevent perinatal transmission from infected mothers to their newborns. All newborns should receive their initial (birthdose) of hepatitis vaccine within twelve hours of birth;

Every person diagnosed with HBV or HCV should have access to and receive a minimum standardized level of care and receive support services;

Strong public education campaigns and improved surveillance must be put in place to help prevent new infections;

Policies must be established to ensure that health care associated hepatitis infections are treated as a "never event";

The investment in hepatitis-related biomedical and behavior must be significantly increased -- and should be more proportionate to the public health threat associated with hepatitis.

Download the full AASLD /Trust For America's Health report HBV & HCV America's Hidden Epidemicshere

InterMune spins of Danoprevir development and commercialization rights to Roche...

Roche Pays InterMune $175M for Rights to Danoprevir

BioWorld Today - Oct. 07, 2010

$530M Deal Axed

InterMune Inc. reported late Wednesday that it sold worldwide development and commercialization rights to danoprevir (RG7227 or ITMN-191) to partner Hoffman-La Roche Inc. and F. Hoffman-La Roche Ltd., of Basel, Switzerland, for $175 million in cash.

In connection with the transaction, the collaboration agreement that Brisbane, Calif.-based InterMune and Roche entered into in October 2006, valued at a potential $530 million, has been terminated. In addition, the companies are actively exploring ways to continue their ongoing work together on other hepatitis C virus research programs. (See BioWorld Today, Oct. 18, 2006.)

With the net proceeds from the transaction, InterMune expects to have a cash balance of about $290 million at the end of 2010.

InterMune's Dan Welch, chairman, CEO and president, said the cash infusion will allow his company to "aggressively pursue" the registration and commercialization of pirfenidone, a drug that failed to win FDA approval as a treatment for idiopathic pulmonary fibrosis despite the strong backing of an agency panel of experts. (See BioWorld Today, May 5, 2010.)

The company's stock (NASDAQ:ITMN) lost 32 cents, to close at $13.45 Wednesday, but following the late-breaking news, was up as much as 9 percent in after-hours trading.

Bye, Bye Zalbin...

From the PharmaLive.com News Archive - Oct. 05, 2010

ROCKVILLE, Md.--(BUSINESS WIRE)--Oct 5, 2010 - Human Genome Sciences, Inc. (Nasdaq: HGSI) today announced that, as expected, it has received a Complete Response Letter (CRL) from the U.S. Food and Drug Administration (FDA) regarding the Company's Biologics License Application (BLA) for 900-mcg ZALBIN™ (albinterferon alfa-2b, known in Europe as JOULFERON®) dosed every two weeks for the treatment of chronic hepatitis C. HGS and Novartis have decided not to develop ZALBIN further.

HGS, Human Genome Sciences and ZALBIN are trademarks of Human Genome Sciences, Inc. Other trademarks referenced are the property of their respective owners.

Medivir Announces Publication of Five TMC435 Abstracts for Presentation at the 61st AASLD Meeting

Cision (English) - Oct. 01, 2010

Medivir Announces Publication of Five TMC435 Abstracts for Presentation at the 61st AASLD Meeting

 Including a Late-breaking Oral Presentation of 24-Week interim data of the TMC435 phase 2b PILLAR study Ë

Medivir AB (OMX: MVIR), a research-based speciality pharmaceutical company focused on infectious diseases, today announces that five abstracts related to its hepatitis C drug in development, TMC435, have been accepted for presentation at the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), taking place from 29 October â?? 2 November 2010 in Boston, USA. The abstracts have been published today and can be accessed on the AASLD website http://www.aasld.org  The accepted titles only are provided below. TMC435, a hepatitis C protease inhibitor, is being jointly developed by Medivir and Tibotec Pharmaceuticals.

At the meeting, in a late-breaking oral presentation, the results from a pre-planned Week 24 interim analysis of the ongoing Phase 2b PILLAR study of TMC435 will be presented. In this study, patients were dosed once-daily with TMC435 in combination with peg interferon a-2a (PegIFN) and ribavirin (RBV) in treatment naive patients infected with HCV genotype 1 (G1). 24-Week interim analysis data will be reported including rapid virologic response (RVR), complete early viral response (cEVR), sustained viral response rates after four weeks (SVR4), and twelve weeks (SVR12) respectively. Secondary endpoints, including the assessment of antiviral activity, viral breakthrough, safety and tolerability, and response rates in IL-28B genotypes, will also be presented.

Additionally, there will be four poster presentations shown at the meeting. Two poster presentations will describe the antiviral activity, safety, tolerability, and pharmacokinetics from a phase 2a open-label, proof-of-concept study of TMC435 in patients infected with HCV genotype 2 to 6.

The other two poster presentations will describe the virologic analysis of G1 infected patients following treatment with once-daily TMC435 in the phase 2a (OPERA-1) study and in vitro studies investigating the mechanism of interaction between TMC435 and hepatic transporters.

Accepted titles for Abstracts to be presented at the 2010 AASLD meeting are as follows:

Late Breaker Oral Presentation for presentation at Monday 1 Nov. 17:45 (EST): LB-5. Efficacy and safety of TMC435 in combination with peginterferon a-2a and ribavirin in treatment-naive genotype-1 HCV patients: 24-week interim results from the PILLAR study.

Poster Presentations: 278. In vitro studies investigating the mechanism of interaction between TMC435 and hepatic transporters. To be presented: Saturday 30 Oct, 14:00 (EST). 812. Virologic analysis of genotype-1-infected patients treated with once-daily TMC435 during the Optimal Protease inhibitor Enhancement of Response to Therapy (OPERA)-1 study.â?? To be presented: Sunday 31 Oct, 08:00 (EST). 895. A Phase 2a, open-label study to assess the antiviral activity of TMC435 monotherapy in patients infected with HCV genotypes 2a.  To be presented: Sunday 31 Oct, 08:00 (EST). 1873. Pharmacokinetic-pharmacodynamic analyses of TMC435 in patients infected with Hepatitis C Virus (HCV) genotypes 2 to 6. To be presented: Tuesday 2 Nov, 07:00 (EST).

Achillion Pharmaceuticals kicks off Phase II trial for ACH-1625 for HCV....

EquityBites - Oct. 01, 2010

Pharmaceutical company Achillion Pharmaceuticals Inc (Nasdaq:ACHN) revealed on Thursday that the company has initiated patient dosing in a Phase II clinical trial of ACH-1625 for the treatment of hepatitis C virus (HCV) infection.

The company added that ACH-1625 is a potent small molecule inhibitor of HCV protease, an enzyme necessary for viral replication.

This Phase IIa, randomised, double-blind, placebo-controlled trial will evaluate the safety, tolerability and antiviral activity of oral ACH-1625 in combination with pegylated interferon alfa-2a and ribavirin after 28 days of dosing and after 12 weeks of dosing in subjects with chronic hepatitis C virus genotype 1.

Additionally, the company stated that the trial will take place in the US and Europe and the data is anticipated in the first and fourth quarters of 2011, respectively.