Vertex Pharmaceuticals - Telaprevir oral and poster presentations at AASLD 2010

Vertex Oral Presentations

November 1, 2010 @ 5:00 p.m. ET

#LB-2 “Telaprevir in Combination with Peginterferon Alfa2a and Ribavirin for 24 or 48 weeks in Treatment-Naïve Genotype 1 HCV Patients who Achieved an Extended Rapid Viral Response: Final Results of Phase 3 ILLUMINATE Study” Hynes Auditorium

November 2, 2010 @ 8:00 a.m. ET

#211 “Telaprevir in Combination with Peginterferon and Ribavirin in Genotype 1 HCV Treatment-Naïve Patients: Final Results of Phase 3 ADVANCE Study” Hynes Auditorium

November 2, 2010 @ 11:45 a.m. ET

#227 “Long-term Follow-up of Patients with Chronic Hepatitis C Treated with Telaprevir in Combination with Peginterferon Alfa-2a and Ribavirin: Interim Analysis of the EXTEND Study” Hynes Room 304/306

Vertex Poster Presentations

October 31, 2010 @ 8:00 a.m. ET

#805 “No Impact of Insulin Resistance on Antiviral Efficacy of Telaprevir-based Regimen in HCV Genotype 1 Treatment-Naïve Patients: Subanalysis of C208 Study” Hynes Exhibit Hall C

#828 “Activity of Telaprevir Monotherapy or in Combination with Peginterferon-alfa-2a and Ribavirin in Treatment-naïve Genotype 4 Hepatitis-C Patients: Final Results of Study C210” Hynes Exhibit Hall C

#1051 “Spontaneous Viral Clearance in a Patient With Chronic Hepatitis C who Relapsed After Telaprevir-based Treatment” Hynes Exhibit Hall C

#899 “The Effect of Hepatitis C Treatment Response on Medical Costs: a 5-Year Longitudinal Analysis in a Managed Care Setting” Hynes Exhibit Hall C

November 1, 2010 @ 8:00 a.m. ET

#LB-11 “Clinical Virology Results from Telaprevir Phase 3 Study ADVANCE” Hynes Exhibit Hall C

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.