ROCKVILLE, Md., Nov. 15 /PRNewswire-FirstCall/ -- Human Genome Sciences, Inc. today announced the interim results of a Phase 2 clinical trial to evaluate the safety, tolerability and efficacy of Albuferon(TM) (albumin-interferon alpha) in combination with ribavirin (RBV) in patients with chronic hepatitis C who failed to respond to previous interferon alpha- based treatment regimens. The results to date demonstrate that Albuferon in combination with RBV was safe, well tolerated and showed robust antiviral activity.
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The results were presented today in San Francisco at the 56th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in an oral presentation entitled “A Phase 2 Study of Albuferon in Combination with Ribavirin in Non-Responders to Prior Interferon Therapy for Chronic Hepatitis C."(1) The trial is a Phase 2, randomized, open-label, multi- center, dose-escalation study, and is being conducted in the United States in patients who have failed to respond to any previous interferon alpha-based treatment regimen. The study design states that approximately 50 percent of the subjects enrolled should be patients who have failed combination therapy that included pegylated interferon alpha plus ribavirin. To date, a total of 115 patients have been enrolled and randomized into 5 Albuferon treatment groups that are receiving doses of Albuferon ranging from 900-1800 mcg.(2) Patients are receiving Albuferon administered subcutaneously at intervals of either 14 or 28 days, with all patients receiving weight-based oral RBV daily at 1000 or 1200 mg in two divided doses. Patients in the trial will receive 48 weeks of treatment, with an additional 24 weeks of follow-up. The primary objective of the Phase 2 study is to evaluate the safety and tolerability of Albuferon in combination with RBV in patients who have not responded to previous treatment with regimens containing interferon alpha or pegylated interferon alpha. The study also is evaluating the efficacy of Albuferon in combination with RBV. The primary efficacy endpoint is sustained virologic response (SVR), defined as undetectable virus at 24 weeks after the end of therapy.
Data were presented today through Week 24 of the 48-week study on 71 patients who were enrolled in parallel and randomized into three Albuferon treatment cohorts: 900 mcg administered subcutaneously every 14 days, 1200 mcg administered subcutaneously every 14 days, and 1200 mcg administered subcutaneously every 28 days -- with all patients receiving weight-based oral RBV daily at 1000 or 1200 mg in two divided doses. 64.8% (46/71) of the study subjects were non-responders to pegylated interferon alpha, and 93% (66/71) were infected with genotype 1 hepatitis C. More than 60% of the study subjects had received more than one prior interferon alpha-based treatment regimen, and the mean duration of prior therapy was approximately 15 months.
At Week 24, 30% of the patients had no detectable hepatitis C RNA viral load. (The primary efficacy endpoint is SVR, defined as undetectable virus at 24 weeks after the end of 48 weeks of therapy.) Antiviral activity was similar for the 14-day and 28-day Albuferon treatment cohorts. Albuferon in combination with RBV was well tolerated. The most common adverse events were fatigue, headache, myalgia and nausea. No significant increase in the severity of adverse events was observed between Week 12 and Week 24, and incidence of adverse events was similar across the three dose cohorts for which data are available. No subject required discontinuation of either Albuferon or RBV for hematological abnormalities. Six subjects developed newly emergent antibodies to interferon alpha; no subject developed treatment- emergent antibodies to human serum albumin. There was no apparent correlation between the emergence of antibodies and antiviral response, adverse events or pharmacokinetics.
David Nelson, M.D., a lead investigator in the Phase 2 study, and Associate Professor of Medicine, Medical Director of Liver Transplantation, and Chief of the Hepatobiliary Diseases Section, University of Florida, Gainesville, said, “The interim data presented today at the AASLD meeting demonstrate that Albuferon in combination with ribavirin was well tolerated and exhibited a robust antiviral activity in this treatment-experienced patient population, with a pharmacokinetic profile that supports dosing at intervals of two to four weeks. We observed that 30% of the patients in the current study had no detectable HCV viral load at Week 24, with little difference in antiviral activity between the 14-day and 28-day Albuferon treatment cohorts. Based on the clinical and preclinical evidence to date(3- 11), we look forward to continuing the evaluation of Albuferon in combination with ribavirin at higher doses and over the full term of the current study.”
David C. Stump, M.D., Executive Vice President, Drug Development, said, “The interim results presented at AASLD today are strongly supportive of our broadening program of clinical study of Albuferon’s potential role as an important therapeutic option for the treatment of hepatitis C.(12) Nearly two thirds of the study population were non-responders to previous treatment with regimens that included pegylated interferon alpha, with more than 60% of the study participants having received more than one prior interferon alpha-based treatment regimen. I am encouraged that approximately 30% of these heavily pretreated patients exhibited no detectable hepatitis C RNA viral load after 24 weeks and that the antiviral activity was robust and similar for the Albuferon treatment cohorts dosed at 14-day and 28-day intervals. The data show that Albuferon in combination with ribavirin was well tolerated, with transient adverse events that were mostly mild to moderate in severity, and with no discontinuations due to adverse events. The rates of newly emergent antibodies to interferon alpha were consistent with those reported for other interferon alpha-based therapies, with no apparent correlation between the emergence of these antibodies and adverse events, antiviral response or pharmacokinetics. We look forward to presentation of additional interim results from the current study, including data from higher-dose cohorts, at an appropriate scientific meeting in the first half of 2006.”
The results of a Phase 2 clinical trial of Albuferon monotherapy in interferon alpha-naive patients with genotype 1 chronic hepatitis C were presented in April 2005 at the 40th Annual Meeting of the European Association for the Study of the Liver (EASL).(5-6) Data presented on 56 patients demonstrated that Albuferon exhibited robust antiviral activity in genotype 1 HCV. A mean reduction in HCV viral load of 3.2 log at Day 28 was observed in the combined 900 mcg and 1200 mcg dose cohorts, with 69% of patients (18/26) in these cohorts showing a >2-log reduction in HCV viral load at Day 28. Undetectable viral load was observed at Day 42 (28 days after the second injection) in 23% of patients (6/26) in the combined 900 mcg and 1200 mcg dose cohorts. Robust dose-dependent viral kinetics were observed, with the majority of patients in the 900 mcg and 1200 mcg cohorts exhibiting a second- phase decline in viral load of >0.3 log per week, which has previously been shown to be predictive of sustained virologic response (SVR) in treatment with the pegylated interferons.(13) Reductions in viral load of equal to or greater than 2 log are reported in approximately 42% of genotype 1 HCV patients treated with pegylated interferon alpha products in combination with ribavirin.(14) The results presented at EASL demonstrate that Albuferon remained in the blood substantially longer than is reported for recombinant interferon alpha and pegylated interferon alpha. Albuferon exhibited a median half-life of 148 hours, supporting dosing at intervals of 2-4 weeks. This compares with a reported mean (range) elimination half-life of 80 hours (50- 140 hours) for Pegasys and 40 hours (22-60 hours) for PEG-Intron.(15-16) Albuferon was well tolerated with adverse events that were transient and mostly mild to moderate in severity. There were no discontinuations due to reductions in hematologic cell counts. No subjects developed newly emergent antibodies to alpha interferon.
Human Genome Sciences has completed enrollment and initial dosing in a larger Phase 2b clinical trial to evaluate the efficacy and safety of Albuferon in combination with ribavirin in patients with HCV genotype 1 who are naive to interferon alpha-based treatment regimens.(12) A total of 458 patients have been enrolled in the randomized, open-label, multi-center, active-controlled, dose-ranging study, which is being conducted in Australia, Canada, Czech Republic, France, Germany, Israel, Poland and Romania. Patients have been randomized into four treatment groups, three of which receive subcutaneously administered Albuferon (900 mcg at 14-day intervals, 1200 mcg at 14-day intervals, and 1200 mcg at 28-day intervals). The fourth treatment group serves as the active control group and receives weekly 180-mcg doses of subcutaneously administered Pegasys (peginterferon alfa-2a). All patients receive weight-based oral daily ribavirin at 1000 or 1200 mg in two divided doses.
Albuferon is a novel, long-acting form of interferon alpha. It is a Human Genome Sciences drug made possible by the company’s proprietary albumin fusion technology, which was used to improve the pharmacological properties of interferon alpha. Recombinant interferon alpha is approved for the treatment of hepatitis C, hepatitis B and a broad range of cancers. Human Genome Sciences is developing Albuferon for use in the treatment of chronic hepatitis C.
Hepatitis C infection is an inflammation of the liver caused by the hepatitis C virus. It is the most common chronic blood-borne infection in the developed world. It is estimated that as many as 170 million people worldwide are infected with hepatitis C virus. This includes nearly four million people in the United States. The hepatitis C virus is transmitted primarily through significant or repeated exposures to infected blood. Intravenous drug use and sexual contact with infected persons account for the majority of new hepatitis C infections. When detectable levels of the hepatitis C virus in the blood persist for at least six months, a person is diagnosed as having chronic hepatitis C.
Human Genome Sciences is a company with the mission to discover, develop, manufacture and market innovative drugs that serve patients with unmet medical needs, with a primary focus on protein and antibody drugs.
For more information about Albuferon, see http://www.hgsi.com/products/albuferon.html. Health professionals interested in more information about trials involving Human Genome Sciences products are encouraged to inquire via the Contact Us section of the company’s web site, http://www.hgsi.com/products/request.html, or by calling (301) 610-5790, extension 3550.
HGS, Human Genome Sciences and Albuferon are trademarks of Human Genome Sciences, Inc.
This announcement contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. The forward-looking statements are based on Human Genome Sciences’ current intent, belief and expectations. These statements are not guarantees of future performance and are subject to certain risks and uncertainties that are difficult to predict. Actual results may differ materially from these forward-looking statements because of the Company’s unproven business model, its dependence on new technologies, the uncertainty and timing of clinical trials, the Company’s ability to develop and commercialize products, its dependence on collaborators for services and revenue, its substantial indebtedness and lease obligations, its changing requirements and costs associated with planned facilities, intense competition, the uncertainty of patent and intellectual property protection, the Company’s dependence on key management and key suppliers, the uncertainty of regulation of products, the impact of future alliances or transactions and other risks described in the Company’s filings with the Securities and Exchange Commission. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of today’s date. Human Genome Sciences undertakes no obligation to update or revise the information contained in this announcement whether as a result of new information, future events or circumstances or otherwise.
Footnotes: 1. Nelson DR, et al. A Phase 2 study of Albuferon in combination with ribavirin in non-responders to prior interferon therapy for chronic hepatitis C. 56th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), 2005. Oral Presentation #204. 2. It is important to note that the method of measurement for dose determination in the Phase 2 study of Albuferon in combination with ribavirin in treatment-experienced patients (as well as in other Phase 2 studies of the compound) is different from the method of measurement in the Phase 1/2 study of Albuferon. Accordingly, the 900-mcg dose in the current study is equivalent to a 680-mcg dose in the Phase 1/2 study, and the 1200-mcg dose is equivalent to 900 mcg in the Phase 1/2 study. 3. Liu C, Zhu H, Xu Y, Nelson DR, et al. Albuferon(TM) exhibits efficient anti-HCV activity in cell culture. Digestive Disease Week (DDW) 2005, Chicago. Abstract #S920. 4. (HGSI Press Release) Human Genome Sciences Reports Results of Preclinical Study Comparing Anti-Viral Activity of Albuferon and Three Other Forms of Interferon Alpha Used to Treat Hepatitis C. May 17, 2005. 5. Bain V, et al. A Phase 2 study to assess antiviral response, safety, and pharmacokinetics of Albuferon in IFNalpha-naive subjects with genotype 1 chronic hepatitis C. 40th Annual Meeting of the European Association for the Study of the Liver (EASL), Paris. April 14, 2005. Oral presentation. Abstract #18. 6. (HGSI Press Release) Human Genome Sciences Reports Positive Results of Phase 2 Clinical Trial of Albuferon in Treatment-Naive Patients with Chronic Hepatitis C. April 14, 2005. 7. Moore P, Balan V, et al. Modulation of interferon specific gene expression by Albuferon in subjects with chronic hepatitis C and correlation with anti-viral response. 40th Annual Meeting of the European Association for the Study of the Liver (EASL), Paris. April 14, 2005. Abstract #447. 8. Balan V, et al. Albuferon(TM) -- A Novel Therapeutic Agent for Hepatitis C: Results of a Phase 1/2 Study in Treatment Experienced Subjects with Chronic Hepatitis C. 55th Annual Meeting of the American Association for the Study of Liver Diseases, Boston. November 2, 2004. Oral presentation Abstract #265. 9. (HGSI Press Release) Human Genome Sciences Reports Positive Results of Phase 1/2 Clinical Trial of Albuferon(TM) in Chronic Hepatitis C. November 2, 2004. 10. Balan V, et al. Molecular profiles of drug response in HCV infected patients during the first four weeks of therapy for chronic hepatitis C virus with pegylated interferon containing regimens or Albuferon. 54th Annual Meeting of the American Association for the Study of Liver Diseases, Boston. October 25, 2003. 11. Osborn B, Olsen H, Nardelli B, et al. Pharmacokinetic and pharmacodynamic studies of a human serum albumin-interferon-a fusion protein in cynomolgus monkeys. J Pharmacol Exp Ther 2002: Nov; 303: 540-548. 12. (HGSI Press Release) Human Genome Sciences Completes Patient Enrollment in a Phase 2b Clinical Trial of Albuferon in Combination with Ribavirin in Treatment-Naive Patients with Chronic Hepatitis C. October 25, 2005. 13. Neumann AU et al. The second phase HCV decline slope is the best predictor of sustained viral response during treatment of chronic HCV genotype 1 patients with peg-interferon-a-2b and ribavirin. 53rd Annual Meeting of the American Association for the Study of Liver Diseases, Boston. November 1-5, 2002. Abstract #778. Hepatology 2002: Vol 36 No 4, Pt 2 of 2. 14. Di Bisceglie AM, Rustgi VK, Thuluvath P, et al. Pharmacokinetics and pharmacodynamics of pegylated interferon alfa-2a or alfa-2b with ribavirin in treatment naive patients with genotype 1 chronic hepatitis C. Hepatology 2004;40,4;734a, abstract LB18. 15. PEGASYS(R) Physicians Desk Reference. (Last updated December 2003). 16. PEG-INTRON(R) Physicians Desk Reference. (Last updated February 2005).
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