Antisense Drug Demonstrates Substantial Reduction Of Viral Load in Patients With Drug Resistant Hepatitis C Virus
Phase I/II Study Shows Dose-Dependent Reduction of Viral Levels
CARLSBAD, Calif., June 18, 2001 -- PRNewswire -- In a Phase I/II clinical trial, ISIS 14803 demonstrated dose-dependent antiviral activity, decreasing viral titers, or level of virus in blood, in patients with drug resistant chronic Hepatitis C Virus (HCV). All patients in the clinical study had the most common and drug resistant form of HCV, genotype 1, and all but one patient had failed previous interferon-based therapy. Results from this study were reported at the American Association for the Study of Liver Diseases' Single Topic Conference on Hepatitis C this weekend in Chicago, by John G. McHutchison, M.D., Medical Director, Liver Transplantation, Division of Gastroenterology/Hepatology, of the Scripps Clinic in La Jolla, California. ISIS 14803 is an antisense drug that inhibits HCV replication and is being developed by HepaSense(TM), Ltd., a joint venture of Isis Pharmaceuticals, Inc. (Nasdaq: ISIP) ("Isis") and Elan Corporation plc. (NYSE: ELN) ("Elan"), of Dublin, Ireland. "The anti-HCV activity demonstrated by this drug at this early stage of clinical development is impressive.
In the trial, we observed responses in patients who were resistant to currently available treatments," said Dr. McHutchison. "While this study involved a small number of patients, we are encouraged by these early results." In the study, 11 patients with genotype 1 HCV, 10 of whom had failed interferon or interferon and ribavirin therapy, were treated with escalating doses of up to 2 mg/kg intravenously of ISIS 14803, three times a week, for one month. Three patients received 0.5 mg/kg, three were treated with 1.0 mg/kg and five were given 2.0 mg/kg, of ISIS 14803. Two of four evaluable patients in the 2 mg/kg group had greater than one log (1.4 and 1.5 log), or 30-fold, decrease in viral titers. A third patient receiving 2mg/kg experienced a half log, or three-fold, reduction. A fourth patient, who received 0.5 mg/kg, experienced a 0.7 log reduction in viral titers. Responses developed after several doses of ISIS 14803 and persisted for a range of 20 to 50 days. In most cases, the responses were associated with a transient liver enzyme "flare," or an increase in alanine aminotransferase (ALT). ISIS 14803 was well tolerated in the Phase I/II clinical trial.
Adverse events reported were minor and non-specific. ALT flares were not accompanied by changes in bilirubin, albumin, or prothrombin time, which are measures of liver synthetic function. Liver biopsy results obtained during an ALT flare did not show evidence of drug-related liver toxicity. "Although the number of patients studied to date is small, we believe ISIS 14803 may prove to be important in the treatment of chronic HCV. In this trial, after a short course of therapy, we observed considerable viral reduction in drug resistant patients with high viral titers. Those reductions appear to correlate with drug dose," said F. Andrew Dorr, M.D., Isis' Vice President and Chief Medical Officer. "Based on the results of this study, we plan to continue to evaluate the potential of ISIS 14803 in single-agent trials, in combination studies with pegylated interferon and ribavirin as well as through studies that will look at longer-term dosing with both intravenous and subcutaneous administration." Studies of the subcutaneous delivery of ISIS 14803 are currently being conducted.
Clinical trials of ISIS 14803 using Elan's MEDIPAD(TM) Drug Delivery System, a minimally invasive microinfusion pump, are planned for the future. In January 2000, Isis and Elan formed HepaSense to jointly develop ISIS 14803 to treat patients with chronic HCV. Hepatitis C causes chronic inflammation of the liver that can go undetected for months or years but is frequently progressive, resulting in life-threatening impairment of liver function. Persistent liver inflammation causes ongoing injury to the cells of the liver. If left untreated, it can lead to liver scarring called cirrhosis, liver failure, possibly liver cancer and death due to the complications of these hepatic insults. Liver complications of chronic HCV infections are the most frequent indication for liver transplantation. According to the National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK), HCV is one of the most important causes of chronic liver disease in the U. S. It accounts for approximately 20 percent of acute viral hepatitis, 60 to 70 percent of chronic hepatitis, and 30 percent of cirrhosis, end-stage liver disease, and liver cancer.
Nearly four million Americans, or 1.8 percent of the U.S. population, have antibody to HCV (anti-HCV), indicating ongoing or previous infection with the virus. There are at least 6 major genotypes and more than 50 subtypes of HCV. Genotypes 1a and 1b are the most common in the U.S. Genotypes 2 and 3 are present in approximately 30 percent of patients. There is little difference in the severity of disease or outcome of patients infected with different genotypes. However, patients with genotypes 2 and 3 are more likely to respond to alpha interferon treatment. HCV causes an estimated 8,000 to 10,000 deaths annually in the U.S. Isis will conduct a live webcast conference call to discuss this release on Monday, June 18, at 10:30 am Eastern time. To participate over the Internet, go to www.streetfusion.com. A replay of the webcast will be available at this address for up to 90 days.
Isis Pharmaceuticals, Inc. is exploiting its expertise in RNA to discover and develop novel human therapeutic drugs. The company has commercialized its first product, Vitravene(TM) (fomivirsen), to treat CMV-induced retinitis in AIDS patients. In addition, Isis has 11 products in its development pipeline, with two in late-stage development and four in Phase II human clinical trials. ISIS 3521, an inhibitor of PKC-alpha, is in Phase III trials for non-small cell lung cancer. Isis is preparing to initiate a Phase III program for ISIS 2302 (alicaforsen), an ICAM-1 inhibitor, in Crohn's disease. Isis has a broad patent estate, as the owner or exclusive licensee of over 780 issued patents worldwide. Isis' GeneTrove division uses antisense to assist pharmaceutical industry partners in validating and prioritizing potential gene targets through customized services and access to an extensive gene function database. Ibis Therapeutics(TM) is a division focused on the discovery of small molecule drugs that bind to RNA.
This press release contains forward-looking statements concerning the profile and development of ISIS 14803 and its prospects. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics. Actual results could differ materially from those projected in this release. As a result, the reader is cautioned not to rely on these forward-looking statements. These and other risks concerning Isis' research and development programs are described in additional detail in Isis' Annual Report on Form 10K-A for the year ended December 31, 2000, which is on file with the U.S. Securities and Exchange Commission, copies of which are available from the company.
HepaSense(TM) is a trademark of HepaSense, Ltd.
Vitravene(TM) is a trademark of Novartis AG.
GeneTrove(TM) and Ibis Therapeutics(TM) are trademarks of Isis Pharmaceuticals, Inc.
MEDIPAD(TM) is a trademark of Elan Corporation, plc.
SOURCE Isis Pharmaceuticals, Inc. Web Site: www.isip.com
Copyright 1996-2001 PR Newswire Association Inc.
Phase I/II Study Shows Dose-Dependent Reduction of Viral Levels
CARLSBAD, Calif., June 18, 2001 -- PRNewswire -- In a Phase I/II clinical trial, ISIS 14803 demonstrated dose-dependent antiviral activity, decreasing viral titers, or level of virus in blood, in patients with drug resistant chronic Hepatitis C Virus (HCV). All patients in the clinical study had the most common and drug resistant form of HCV, genotype 1, and all but one patient had failed previous interferon-based therapy. Results from this study were reported at the American Association for the Study of Liver Diseases' Single Topic Conference on Hepatitis C this weekend in Chicago, by John G. McHutchison, M.D., Medical Director, Liver Transplantation, Division of Gastroenterology/Hepatology, of the Scripps Clinic in La Jolla, California. ISIS 14803 is an antisense drug that inhibits HCV replication and is being developed by HepaSense(TM), Ltd., a joint venture of Isis Pharmaceuticals, Inc. (Nasdaq: ISIP) ("Isis") and Elan Corporation plc. (NYSE: ELN) ("Elan"), of Dublin, Ireland. "The anti-HCV activity demonstrated by this drug at this early stage of clinical development is impressive.
In the trial, we observed responses in patients who were resistant to currently available treatments," said Dr. McHutchison. "While this study involved a small number of patients, we are encouraged by these early results." In the study, 11 patients with genotype 1 HCV, 10 of whom had failed interferon or interferon and ribavirin therapy, were treated with escalating doses of up to 2 mg/kg intravenously of ISIS 14803, three times a week, for one month. Three patients received 0.5 mg/kg, three were treated with 1.0 mg/kg and five were given 2.0 mg/kg, of ISIS 14803. Two of four evaluable patients in the 2 mg/kg group had greater than one log (1.4 and 1.5 log), or 30-fold, decrease in viral titers. A third patient receiving 2mg/kg experienced a half log, or three-fold, reduction. A fourth patient, who received 0.5 mg/kg, experienced a 0.7 log reduction in viral titers. Responses developed after several doses of ISIS 14803 and persisted for a range of 20 to 50 days. In most cases, the responses were associated with a transient liver enzyme "flare," or an increase in alanine aminotransferase (ALT). ISIS 14803 was well tolerated in the Phase I/II clinical trial.
Adverse events reported were minor and non-specific. ALT flares were not accompanied by changes in bilirubin, albumin, or prothrombin time, which are measures of liver synthetic function. Liver biopsy results obtained during an ALT flare did not show evidence of drug-related liver toxicity. "Although the number of patients studied to date is small, we believe ISIS 14803 may prove to be important in the treatment of chronic HCV. In this trial, after a short course of therapy, we observed considerable viral reduction in drug resistant patients with high viral titers. Those reductions appear to correlate with drug dose," said F. Andrew Dorr, M.D., Isis' Vice President and Chief Medical Officer. "Based on the results of this study, we plan to continue to evaluate the potential of ISIS 14803 in single-agent trials, in combination studies with pegylated interferon and ribavirin as well as through studies that will look at longer-term dosing with both intravenous and subcutaneous administration." Studies of the subcutaneous delivery of ISIS 14803 are currently being conducted.
Clinical trials of ISIS 14803 using Elan's MEDIPAD(TM) Drug Delivery System, a minimally invasive microinfusion pump, are planned for the future. In January 2000, Isis and Elan formed HepaSense to jointly develop ISIS 14803 to treat patients with chronic HCV. Hepatitis C causes chronic inflammation of the liver that can go undetected for months or years but is frequently progressive, resulting in life-threatening impairment of liver function. Persistent liver inflammation causes ongoing injury to the cells of the liver. If left untreated, it can lead to liver scarring called cirrhosis, liver failure, possibly liver cancer and death due to the complications of these hepatic insults. Liver complications of chronic HCV infections are the most frequent indication for liver transplantation. According to the National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK), HCV is one of the most important causes of chronic liver disease in the U. S. It accounts for approximately 20 percent of acute viral hepatitis, 60 to 70 percent of chronic hepatitis, and 30 percent of cirrhosis, end-stage liver disease, and liver cancer.
Nearly four million Americans, or 1.8 percent of the U.S. population, have antibody to HCV (anti-HCV), indicating ongoing or previous infection with the virus. There are at least 6 major genotypes and more than 50 subtypes of HCV. Genotypes 1a and 1b are the most common in the U.S. Genotypes 2 and 3 are present in approximately 30 percent of patients. There is little difference in the severity of disease or outcome of patients infected with different genotypes. However, patients with genotypes 2 and 3 are more likely to respond to alpha interferon treatment. HCV causes an estimated 8,000 to 10,000 deaths annually in the U.S. Isis will conduct a live webcast conference call to discuss this release on Monday, June 18, at 10:30 am Eastern time. To participate over the Internet, go to www.streetfusion.com. A replay of the webcast will be available at this address for up to 90 days.
Isis Pharmaceuticals, Inc. is exploiting its expertise in RNA to discover and develop novel human therapeutic drugs. The company has commercialized its first product, Vitravene(TM) (fomivirsen), to treat CMV-induced retinitis in AIDS patients. In addition, Isis has 11 products in its development pipeline, with two in late-stage development and four in Phase II human clinical trials. ISIS 3521, an inhibitor of PKC-alpha, is in Phase III trials for non-small cell lung cancer. Isis is preparing to initiate a Phase III program for ISIS 2302 (alicaforsen), an ICAM-1 inhibitor, in Crohn's disease. Isis has a broad patent estate, as the owner or exclusive licensee of over 780 issued patents worldwide. Isis' GeneTrove division uses antisense to assist pharmaceutical industry partners in validating and prioritizing potential gene targets through customized services and access to an extensive gene function database. Ibis Therapeutics(TM) is a division focused on the discovery of small molecule drugs that bind to RNA.
This press release contains forward-looking statements concerning the profile and development of ISIS 14803 and its prospects. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics. Actual results could differ materially from those projected in this release. As a result, the reader is cautioned not to rely on these forward-looking statements. These and other risks concerning Isis' research and development programs are described in additional detail in Isis' Annual Report on Form 10K-A for the year ended December 31, 2000, which is on file with the U.S. Securities and Exchange Commission, copies of which are available from the company.
HepaSense(TM) is a trademark of HepaSense, Ltd.
Vitravene(TM) is a trademark of Novartis AG.
GeneTrove(TM) and Ibis Therapeutics(TM) are trademarks of Isis Pharmaceuticals, Inc.
MEDIPAD(TM) is a trademark of Elan Corporation, plc.
SOURCE Isis Pharmaceuticals, Inc. Web Site: www.isip.com
Copyright 1996-2001 PR Newswire Association Inc.
