Healthcare Industry News: Novartis Pharma AG
News Release - April 29, 2006
Favorable Antiviral Activity and Improved Tolerability Demonstrated by Valopicitabine 200 mg/day in Combination with Pegylated Interferon in an Ongoing Phase IIb Trial in Treatment-Naive Genotype 1 PatientsData at 12 and 16 weeks show comparable activity to 800 mg/day dose
VIENNA, Austria and CAMBRIDGE, Mass., April 29 (HSMN NewsFeed) -- Idenix Pharmaceuticals, Inc. (Nasdaq: IDIX ) announced today that the 200 mg/day dose level of the investigational agent, valopicitabine (NM283), combined with pegylated interferon demonstrated comparable antiviral activity to the results obtained in the 800 mg/day-containing arms in a preliminary analysis of an ongoing phase IIb clinical trial in treatment-naive genotype 1 patients at 12 weeks of treatment. To date in this clinical trial the 200 mg/day dose has demonstrated improved tolerability compared to the 800 mg/day dose. These data are being presented in a late-breaker session on Saturday, April 29 at 5:15 p.m. Central European Time (CET) at the annual meeting of the European Association for the Study of the Liver.
"The antiviral activity and safety data observed in the 200 mg/day dose arm is encouraging," said Douglas Dieterich, M.D., Professor of Medicine at the Mt. Sinai School of Medicine, New York and an investigator in the study. "More than 70 percent of patients receiving this regimen achieved viral clearance at week 12 utilizing the Amplicor® assay's lower limit of quantification of 600 copies/mL, which is substantially higher than we generally see in clinical practice in HCV genotype 1 patients."
"We believe these data indicate that valopicitabine may provide significant viral suppression and may be well tolerated at the 200 mg/day dose," said Jean-Pierre Sommadossi, Ph.D., chairman and chief executive officer of Idenix Pharmaceuticals, Inc. "We are planning a robust program to advance the development of valopicitabine and believe, if successfully developed and approved, it may become an important component of future HCV combination therapy to improve treatment for patients."
In the 200 mg/day arm (arm B*; n=31), 87 percent of patients achieved an early virologic response (EVR), defined as greater than or equal to 2 log10 (100-fold) reduction in virus after 12 weeks of treatment, compared to 88 percent in the pooled 800 mg/day arms (arms C, D and E*; n=92). At 12 and 16 weeks, 71 percent and 73 percent, respectively, of patients in the 200 mg/day arm reached undetectable virus levels below 600 copies/mL compared to 73 percent and 74 percent in the pooled 800 mg/day arms. After 12 and 16 weeks, 45 percent and 62 percent, respectively, of patients in the 200 mg/day arm reached undetectable virus levels below 20 copies/mL, compared to 56 percent and 61 percent in the pooled 800 mg/day arms. Mean reductions of HCV RNA of 3.93 log10 after 12 weeks of treatment were achieved among patients in the 200 mg/day dose group compared to 4.26 log10 in the pooled 800 mg/day dosing groups. Partial 16-week data indicated above includes 26 patients in the 200 mg/day arm and 74 patients in the pooled 800 mg/day arms.
Through 12 weeks of treatment, in the ongoing phase IIb clinical trial, discontinuations in the 200 mg/day arm occurred at a rate significantly less than the higher dosing regimens, at six percent and 22 percent, respectively. Through week 12, a total of 24 patients discontinued for adverse events (AEs), with two occurring in the 200 mg/day arm. To date, three serious adverse events (SAEs) were considered attributable to valopicitabine in the phase IIb clinical trial. These were dehydration with renal insufficiency and pancreatitis; hyponatremia/hypokalemia; and dehydration with acute gastroenteritis. Two of these SAEs occurred at doses of 800 mg/day and one occurred at a dose of 200 mg/day.
*Phase IIb Study Design
The 12-week analysis from this ongoing 48-week phase IIb clinical trial in treatment-naive patients included data from the following five randomized treatment arms, all involving dosing regimens of valopicitabine, administered once-daily, in combination with pegylated interferon alfa-2a (Pegasys®) 180 µg per week: (A) pegylated interferon beginning on Day 8 plus valopicitabine ramping from 400 mg to 800 mg beginning at Day 29; (B) valopicitabine 200 mg beginning on Day 1 plus pegylated interferon beginning on Day 8; © valopicitabine ramping from 400 mg to 800 mg beginning on Day 1 plus pegylated interferon beginning on Day 8; (D) valopicitabine 800 mg beginning on Day 1 plus pegylated interferon beginning on Day 8; and (E) valopicitabine 800 mg plus pegylated interferon, both beginning on Day 1.
In March 2006, the protocol for this ongoing phase IIb 48-week clinical trial in treatment-naive patients was amended after gastrointestinal side effects related primarily to the higher dose arms (800 mg/day) of valopicitabine were observed. The amendment required that patients in the 800 mg/day dose arms who had virus levels below 600 IU/mL, be randomized to continue study treatment with either valopicitabine 200 mg/day plus pegylated interferon or valopicitabine 400 mg/day plus pegylated interferon. Twelve percent of the treatment-naive patients did not meet the criteria and were discontinued from the trial. Patients originally receiving the 200 mg/day dose have continued on that treatment regimen. The 12-week data discussed herein includes data prior to protocol modifications.
More About Valopicitabine
Valopicitabine is an investigational agent being evaluated in ongoing clinical trials for the treatment of hepatitis C. Based on preclinical evidence, it is believed that valopicitabine may block hepatitis C virus (HCV) replication by specifically inhibiting the HCV RNA polymerase. In initial clinical trials, valopicitabine, administered orally once a day, was shown to reduce HCV viremia in patients infected with the genotype 1 strain of HCV. The ongoing phase IIb clinical trials are evaluating the combination of valopicitabine and pegylated interferon in hepatitis C patients who previously failed to respond to antiviral treatment, as well as in patients who have not yet been treated for hepatitis C. Valopicitabine has dose-related gastrointestinal (GI) side effects, more common at higher dosing levels (e.g., 800 mg/day), which are typically mild-to-moderate, are transient in most patients, and are less common at lower dosing levels (200 mg/day and 400 mg/day). Moderate or severe intensity to the gastrointestinal side effects have been observed in some patients, particularly at higher dosing levels, which may result in treatment discontinuation.
About Hepatitis C
Hepatitis C is an infectious liver disease caused by the hepatitis C virus.(1) Chronic HCV infection inflames the liver, causing progressive liver damage that can lead to cirrhosis (liver scarring), hepatocellular carcinoma (liver cancer), liver failure and death.(1) Hepatitis C is a severe and progressive disease, with 70 percent to 85 percent of patients infected with HCV developing chronic infection,(2) and of whom 10 percent to 20 percent develop cirrhosis.(1) Worldwide, the World Health Organization estimates that 170 million individuals carry chronic HCV infection, with 3 to 4 million new infections each year.(1)
HCV infection is the most common chronic blood-borne infection in the United States.(3) The Centers for Disease Control and Prevention estimates that 4 million Americans have been infected with HCV, and 2.7 million of these carry chronic HCV infections.(2) Hepatitis C related liver failure is the most common indication for liver transplantation in the United States.(2) As the prevalence of severe liver disease attributable to hepatitis C rises, deaths due to complications from hepatitis C infection, currently 8,000 to 10,000 per year in the United States, are increasing and are expected to triple by 2010.(4)
Idenix is developing its hepatitis B and hepatitis C product candidates, telbivudine, valtorcitabine and valopicitabine, in collaboration with Novartis Pharma AG. The collaboration arrangement provides that Novartis and Idenix will co-promote in the United States, France, Germany, Italy, Spain and the United Kingdom those product candidates that are approved for marketing, which Novartis has licensed. Novartis holds the exclusive license to these product candidates in the rest of the world.
Idenix Pharmaceuticals, Inc. is a biopharmaceutical company engaged in the discovery, development and commercialization of drugs for the treatment of human viral and other infectious diseases. Idenix's current focus is on the treatment of infections caused by hepatitis B virus, hepatitis C virus and human immunodeficiency virus (HIV). Idenix's headquarters are located in Cambridge, Massachusetts and it has drug discovery and development operations in Montpellier, France and drug discovery operations in Cagliari, Italy. For further information about Idenix, please refer to http://www.idenix.com.
This press release contains "forward-looking statements" within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward- looking statements can be identified by the use of forward-looking terminology such as "is encouraging", "believe", "may", "planning", or similar expressions or by express or implied discussions regarding the ongoing and planned clinical trial development of valopicitabine, regarding potential future marketing approvals for valopicitabine or potential future sales of valopicitabine. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantees that valopicitabine will successfully complete phase IIb clinical evaluation in both or either patient population in which it is currently being evaluated or that valopicitabine will proceed to phase III clinical trials in any patient population. Neither can there be any guarantees that valopicitabine will be approved by regulatory authorities in any markets, or that the company will earn any revenues from valopicitabine. In particular, management's expectations may be affected by the results of clinical trials, including additional data relating to the ongoing phase IIb clinical trial evaluating valopicitabine; unexpected regulatory actions or delays or government regulation generally; the company's ability to obtain additional funding required to conduct its research, development and commercialization activities; the ability of the company to attract and retain qualified personnel; competition in general; government, industry and general public pricing pressures; and the company's ability to obtain, maintain and enforce patent and other intellectual property protection for valopicitabine. These and other risks which may impact management's expectations are described in greater detail under the caption "Risk Factors" in the company's annual report on Form 10-K for the year ended December 31, 2005 and filed with the Securities and Exchange Commission and other filings that the company makes with the Securities and Exchange Commission.
All forward-looking statements reflect the company's expectations only as of the date of this release and should not be relied upon as reflecting the company's views, expectations or beliefs at any date subsequent to the date of this release. Idenix anticipates that subsequent events and developments may cause these views, expectations and beliefs to change. However, while Idenix may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so.
Pegasys® and Amplicor® are registered trademarks of Hoffmann-La Roche, Inc.
(1) World Health Organization. Hepatitis C Fact Sheet accessed online at http://www.who.int/mediacentre/factsheets/fs164/en/print.html
(2) Center for Disease Control. Hepatitis C Fact Sheet accessed online at http://www.cdc.gov/ncidod/diseases/hepatitis/c/fact.htm
(3) Center For Disease Control National Prevention Strategy
(4) Davis, G. et al., Projecting Future Complications of Chronic Hepatitis C in the United States. Liver Transplantation, April 2003
Source: Idenix Pharmaceuticals
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