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.

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.

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.

Anadys Pharmaceuticals ANA598 update - SVR 12 in Phase II looking good!

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 â?? 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-naive 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.

IL28B allele in SOC arm of Anadys Pharmaceuticals ANA598 clinical study leading to a higher cEVR than previously seen in SOC arm?

Anadys Pharmaceuticals announced that it has completed 12-week results from an ongoing Phase II study, which demonstrated that 75% of HCV patients treated with 400 mg ANA598 twice daily in combination with pegylated interferon and ribavirin (current standard of care, or SOC) achieved undetectable levels of virus (1 log from any prior measurement) between weeks 10 and 12. No other patient who received either dose of ANA598 experienced viral breakthrough.


The company can offer additional perspective on the response of the patients who received placebo plus standard of care (control arm) in the study based on a preliminary assessment of IL28B genotyping from approximately 60% of the patients in the Phase II study. Recent scientific studies have shown that individuals with the IL28B CC genotype, present in approximately 37% of Caucasian HCV patients and a lower percentage of patients in other ethnic groups, are substantially more responsive to SOC than patients with other IL28B genotypes. In the SOC control arm of the ANA598 study, 56% of the patients who have been genotyped to date are of the CC genotype while in the ANA598-treated arms only 21% of the patients who have been genotyped to date are of the CC genotype. The company believes that the high proportion of CC patients in the SOC control arm of the ANA598 Phase II study relative to the overall population likely contributed to a higher cEVR rate than has been seen historically.

Source: http://www.anadyspharma.com/pr_pdfs/ana598%20complete%2012-week%20data%20%20final%205.21.10.pdf