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HCV Drug Albuferon Phase 2B Enrollment Completed
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HUMAN GENOME SCIENCES COMPLETES PATIENT ENROLLMENT IN A PHASE 2B CLINICAL TRIAL OF ALBUFERON IN COMBINATION WITH RIBAVIRIN IN TREATMENT-NAìVE PATIENTS WITH CHRONIC HEPATITIS C
Press announcement was distributed today by Human Genome Sciences
ROCKVILLE, Maryland Ð October 25, 2005 Ð Human Genome Sciences, Inc. (Nasdaq: HGSI) announced today that it has completed enrollment, randomization and initial dosing in a Phase 2b clinical trial of Albuferonª (albumin-interferon alpha) in combination with ribavirin in patients with chronic hepatitis C virus (HCV) genotype 1 who are na•ve to interferon alpha-based treatment regimens. Genotype 1 accounts for nearly 70% of all HCV infections in North America and is generally regarded as the most difficult HCV genotype to treat.
The trial is a randomized, open-label, multi-center, active-controlled, dose-ranging study conducted in Australia, Canada, Czech Republic, France, Germany, Israel, Poland and Romania.1 A total of 458 patients with chronic hepatitis C genotype 1 have received initial treatment in the Phase 2b study. 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 intervals2). 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. The primary objectives of the Phase 2b study are to evaluate the efficacy and safety of Albuferon in combination with ribavirin in interferon alpha-na•ve patients with chronic hepatitis C genotype 1. The primary efficacy endpoint is sustained virologic response, defined as undetectable virus at 24 weeks after completion of 48 weeks of treatment.
John McHutchison, M.D., Coordinating Center Principal Investigator for the Phase 2b study, and Professor of Medicine and Director, GI/Hepatology Research, Duke Clinical Research Institute and Duke University Medical Center, Durham, NC, said, ÒThe Phase 2b study of Albuferon in combination with ribavirin in treatment-na•ve patients will build upon preclinical and clinical results to date, which support the continued evaluation of Albuferon in larger populations to define its appropriate therapeutic role in the treatment of chronic hepatitis C. The current standard of care for the treatment of chronic hepatitis C is a combination of pegylated interferon alpha and ribavirin. This combination produces cures in approximately 42-46 percent of all genotype 1 HCV patients completing therapy, leaving more than 50 percent who relapse or do not respond. Clearly, chronic hepatitis C represents a significant unmet medical need. This unmet medical need perhaps explains the rapid enrollment of the Phase 2b study of Albuferon with ribavirin, which exceeded all our expectations.Ó3-12
David C. Stump, M.D., Executive Vice President, Drug Development, said, ÒThe current Phase 2b study is the largest Albuferon trial to date. We plan to take our first look at comparative data from the Phase 2b trial in Spring 2006, after the last patient has completed 12 weeks of treatment. In April 2005, we reported that the results of an earlier Phase 2 study of Albuferon monotherapy in treatment-na•ve patients with genotype 1 hepatitis C demonstrated that Albuferon was well tolerated, had a prolonged half-life and showed robust antiviral activity, with durable dose-dependent reductions in HCV viral load.13-14 These data also enabled our identification of the range of active doses that we are evaluating in the current Phase 2b trial. An additional Phase 2 clinical trial of Albuferon in combination with ribavirin is ongoing in patients who have failed to respond to previous interferon alpha-based treatment regimens.15 We look forward to presentation of interim results from this study in treatment-experienced patients at the annual meeting of the American Association for the Study of Liver Disease (AASLD) in November 2005. Based on the preclinical and clinical results that have emerged thus far16-22, we believe that Albuferon has the potential to become an important therapeutic option for the treatment of chronic hepatitis C.Ó
The results of a Phase 2 clinical trial of Albuferon monotherapy in interferon alpha-na•ve patients with genotype 1 chronic hepatitis C were presented at the 40 th Annual Meeting of the European Association for the Study of the Liver (EASL). 13-14 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.23 Reductions in viral load of > 2 log are reported in approximately 42% of genotype 1 HCV patients treated with pegylated interferon alpha products in combination with ribavirin.24 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.25-26 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.
Albuferon is a novel, long-acting form 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 modified interferon alpha to improve its pharmacological properties by using the companyÕs proprietary albumin fusion technology.
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 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 companyÕs web site, 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 SciencesÕ 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 CompanyÕs unproven business model, its dependence on new technologies, the uncertainty and timing of clinical trials, the CompanyÕs 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 CompanyÕs 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 CompanyÕs 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 todayÕs 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.
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Footnotes:
1. (HGSI Press Release) Human Genome Sciences Initiates Phase 2b Clinical Trial of Albuferon in Combination with Ribavirin in Treatment-Na•ve Patients with Chronic Hepatitis C. June 1, 2005 .
2. It is important to note that the method of measurement for dose determination in the Phase 2b study of Albuferon in combination with ribavirin in treatment-na•ve 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. Manns MP, McHutchison JG, Gordon S, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa 2b plus ribavirin for initial treatment of chronic hepatitis C: a randomized trial. The Lancet 2001; 358:958-65.
4. Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. New England Journal of Medicine 2002; 347:975-982.
5. Carithers RL, Zeuzem S, Manns MP, et al. Multicenter, randomized controlled trial comparing high dose daily induction interferon plus ribavirin versus standard interferon alfa-2b plus ribavirin. Hepatology 2000; 32:3317A (abstr).
6. Zeuzem S. Heterogeneous virologic response rates to interferon-based therapy in patients with chronic hepatitis C: who responds less well? Ann Intern Med 2004; 140:370-381.
7. Alter MJ. Epidemiology of hepatitis C in the West. Semin. Liver Disease. 1995;15:5-14.
8. Strader DB, Wright T, Thomas DL, and Seeff, LB. AASLD Practice Guideline: Diagnosis, Management, and Treatment of Hepatitis C. Hepatology 2004 April; 39 (4): 1147-1171.
9. Hadziyannis SJ, Sette H, Morgan TR, et al. Peginterferon-ƒ¿2a and ribavirin combination therapy in chronic hepatitis C. Ann Intern Med 2004; 140:346-355.
10. Shiffman ML, Di Bisceglie AM, Lindsay KL, et al. Peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C who have failed prior treatment. Gastroenterology 2004; 126:1015-1023.
11. Zeng N, Cohen CK, Schwartz P, Rai R. Treatment of HCV infected patients, including non-responders to PEG-IFN alfa-2b/RBV, with PEG-IFN alfa-2a/RBV: the Johns Hopkins experience. Digestive Disease Week 2004 Internet Conference Report. Abstract #1233.
12. Management of Hepatitis C: 2002. National Institutes of Health Consensus Development Conference.
13. Bain V, et al. A Phase 2 study to assess antiviral response, safety, and pharmacokinetics of Albuferon in IFN a -na•ve subjects with genotype 1 chronic hepatitis C. 40 th Annual Meeting of the European Association for the Study of the Liver (EASL), Paris. April 14, 2005 . Oral presentation. Abstract #18.
14. (HGSI Press Release) Human Genome Sciences Reports Positive Results of Phase 2 Clinical Trial of Albuferon in Treatment-Na•ve Patients with Chronic Hepatitis C. April 14, 2005 .
15. (HGSI Press Release) Human Genome Sciences Initiates Phase 2 Clinical Trial of Albuferon in Combination with Ribavirin in Treatment-Experienced Hepatitis C Patients. November 30, 2004 .
16. Balan V, et al. Albuferonª -- A Novel Therapeutic Agent for Hepatitis C: Results of a Phase 1/2 Study in Treatment Experienced Subjects with Chronic Hepatitis C. 55 th Annual Meeting of the American Association for the Study of Liver Diseases, Boston . November 2, 2004 . Oral presentation Abstract #265.
17. (HGSI Press Release) Human Genome Sciences Reports Positive Results of Phase 1/2 Clinical Trial of Albuferonª in Chronic Hepatitis C. November 2, 2004 .
18. Liu C, Zhu H, Xu Y, Nelson DR, et al. Albuferonª exhibits efficient anti-HCV activity in cell culture. Digestive Disease Week (DDW) 2005, Chicago . Abstract #S920.
19. (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 .
20. 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. 54 th Annual Meeting of the American Association for the Study of Liver Diseases, Boston . October 25, 2003 .
21. 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. 40 th Annual Meeting of the European Association for the Study of the Liver (EASL), Paris. April 14, 2005 . Abstract #447.
22. 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.
23. 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. 53 rd Annual Meeting of the American Association for the Study of Liver Diseases, Boston . November 1-5, 2002 . Abstract #778. Hepatology 2002: 36 (4), Pt 2 of 2.
24. Di Bisceglie AM, Rustgi VK, Thuluvath P, et al. Pharmacokinetics and pharmacodynamics of pegylated interferon alfa-2a or alfa-2b with ribavirin in treatment na•ve patients with genotype 1 chronic hepatitis C. Hepatology 2004;40,4;734a, abstract LB18.
25. PEGASYS¨ Physicians Desk Reference. (Last updated December 2003).
26. PEG-INTRON¨ Physicians Desk Reference. (Last updated February 2005).
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