ROCKVILLE, Md., May 1 /PRNewswire-FirstCall/ -- Human Genome Sciences, Inc. today reported the interim results of a Phase 2 clinical trial to evaluate the safety, tolerability and efficacy of Albuferon(TM) (albumin-interferon alpha 2b) in combination with ribavirin in patients with chronic hepatitis C (HCV) who failed to respond to previous interferon alpha-based treatment regimens. The results to date -- presented over the weekend at the 41st Annual Meeting of the European Association for the Study of the Liver (EASL)(1) -- demonstrate that Albuferon in combination with ribavirin was safe, well tolerated and showed robust and durable antiviral activity. (In a separate press release today, HGS announced the interim results of a larger Phase 2b clinical trial of Albuferon with ribavirin in treatment-naive patients with chronic hepatitis C genotype 1.(2-3))
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Vinod K. Rustgi, M.D., Co-Director of the Transplant Institute at Georgetown University School of Medicine (Washington, DC), and a clinical investigator in the Phase 2 trial, said, “The interim results of the Phase 2 study in treatment non-responders showed that Albuferon was well tolerated, with robust and durable antiviral activity. At Week 48, 31% of the patients in the three lower-dose treatment groups had no detectable hepatitis C RNA viral load. The preliminary rate of sustained virologic response (SVR) in these heavily pretreated patients is surprisingly high at 20%, based on the Week 12 follow-up point after the end of 48 weeks of treatment. The relapse rate is low. Few viral breakthroughs were observed. The treatment group receiving 1200-mcg Albuferon every four weeks was able to maintain HCV RNA negativity. Based on data available through Week 24, the 1800-mcg Albuferon dose cohort showed the highest rates of HCV RNA negativity In genotype 1 patients who previously failed to respond to treatment with pegylated interferon and ribavirin. We look forward to continuing the evaluation of Albuferon in combination with ribavirin over the full term of the current study.”
David C. Stump, M.D., Executive Vice President, Drug Development, Human Genome Sciences, said, “I am encouraged by the emerging evidence of Albuferon’s clinically significant antiviral effect. One of the most important areas of medical need in the treatment of chronic hepatitis C is those patients infected with genotype 1 hepatitis C who have failed previous treatment with the standard-of-care combination of pegylated interferon and ribavirin. In this most difficult to treat subgroup, 63% of the patients receiving 1800-mcg doses of Albuferon once every two weeks achieved early virologic response at Week 12 (EVR12). At Week 24, no detectable HCV RNA viral load was observed in 32% of the genotype 1 non-responders to standard- of-care in the 1800-mcg treatment group. Across the total patient population, the safety data from both of the higher-dose treatment groups was generally similar to safety data from the lower-dose treatment groups, but with greater antiviral activity. These results encourage us to evaluate a regimen in interferon-naive patients that combines higher doses of Albuferon with ribavirin administered at intervals of 28 days.”
The Phase 2 interim results were reported in Vienna yesterday, April 30, 2006, at the 41st Annual Meeting of the European Association for the Study of the Liver (EASL) in an oral presentation entitled “A Phase 2 Dose-Escalation Study of Albumin Interferon Alfa-2b Combined with Ribavirin in Non-Responders to Interferon-Based Therapy for Chronic Hepatitis C Infection."(1) Data are available through Week 60 (48 weeks of treatment plus 12 weeks of follow-up) on 71 patients who were enrolled in parallel and randomized into three Albuferon treatment groups: 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 ribavirin daily at 1000 or 1200 mg in two divided doses.(4) Of the subjects in the first three Albuferon treatment groups, 63% (45/71) 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 48, 31% (22/71) of the patients in the 900-mcg and 1200-mcg Albuferon treatment groups exhibited no detectable HCV RNA viral load. Antiviral activity was similar for the 14-day and 28-day Albuferon treatment groups. At the Week 12 follow-up after the end of treatment, 20% (14/71) of these heavily pretreated patients had no detectable hepatitis C RNA viral load. The primary efficacy endpoint in the trial is sustained virologic response (SVR), defined as undetectable virus 24 weeks after the end of therapy.
The 1800-mcg Albuferon treatment group had a higher percentage of genotype 1 hepatitis C patients who failed to respond to previous treatment with a combination of pegylated interferon and ribavirin -- 91% (20/22) versus an average of 66% (61/93) in the other Albuferon treatment groups combined. At Week 24 in this important and most difficult to treat subgroup, the data show the following percentages of patients with no detectable HCV RNA viral load: 15% (2/13) in the treatment group receiving 1200 mcg of Albuferon at 28-day intervals; 17% (2/12) in the treatment group receiving 900 mcg of Albuferon at 14-day intervals; 19% (3/16) in the treatment group receiving 1200 mcg of Albuferon at 14-day intervals; 27% (4/15) in the treatment group receiving 1500 mcg of Albuferon at 14-day intervals; and 32% (6/19) in the treatment group receiving 1800 mcg of Albuferon at 14-day intervals. Data also are available for this subgroup on early virologic response (EVR12). The data show the following percentages of patients achieving EVR12: 23% (3/13) in the treatment group receiving 1200 mcg of Albuferon at 28-day intervals; 42% (5/12) in the treatment group receiving 900 mcg of Albuferon at 14-day intervals; 25% (4/16) in the treatment group receiving 1200 mcg of Albuferon at 14-day intervals; 33% (5/15) in the treatment group receiving 1500 mcg of Albuferon at 14-day intervals; and 63% (12/19) in the treatment group receiving 1800 mcg of Albuferon at 14-day intervals.
Albuferon in combination with ribavirin was well tolerated. The incidence of adverse events was similar across the three dose groups for which 48-week data are available. No increase in severity of adverse events was observed beyond Week 12. Decreases in hematologic cell counts were maximal by Week 8, were well managed with dose reductions, and returned to baseline following the completion of therapy (Week 12 follow-up after the end of 48 weeks of treatment). Albuferon appeared to be better tolerated in the treatment group receiving 1200 mcg administered subcutaneously every 28 days, with fewer dose reductions due to hematology observed in this group. No subject required discontinuation of either Albuferon or ribavirin for hematological abnormalities. Overall, the rate of treatment-emergent Albuferon antibodies is 10%, with pre-existing antibodies detected in 17% of study participants. There was no apparent correlation between the emergence of antibodies and antiviral response, adverse events or pharmacokinetics. No overall increase in the emergence of antibodies was observed between Week 12, Week 24 and Week 48. Safety data available for the 1500-mcg and 1800-mcg treatment groups through Week 24 are generally similar to the lower-dose Albuferon treatment groups. No increase in the emergence of Albuferon antibodies was observed related to administration of the higher doses.
The Phase 2 trial is a randomized, open-label, multi-center, dose-escalation study of Albuferon in combination with ribavirin in patients who have failed to respond to interferon-based therapy for chronic hepatitis C. The trial is being conducted in the United States. 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. A total of 115 patients have been enrolled into 5 Albuferon treatment groups that are receiving doses of Albuferon ranging from 900-1800 mcg. (1,5-6) Patients were initially randomized into 3 Albuferon treatment groups (900 mcg at 14-day intervals, 1200 mcg at 14-day intervals, and 1200 mcg at 28-day intervals). Following evaluation of safety data, 2 additional cohorts were enrolled sequentially (1500 mcg at 14-day intervals and 1800 mcg at 14-day intervals). Patients are receiving Albuferon administered subcutaneously, with all patients receiving weight-based oral ribavirin 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 ribavirin. The study also is evaluating the efficacy of Albuferon in combination with ribavirin.
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.(1-3, 5-12)
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 HGS 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) Rustgi V, Nelson D, Balan V, McHutchison J, Subramanian M, et al. A Phase 2 dose-escalation study of interferon alfa-2b combined with ribavirin in non-responders to prior interferon-based therapy for chronic hepatitis C infection. 41st Annual Meeting of the European Association for the Study of the Liver (EASL), Vienna. Oral Presentation #113. (2) (HGSI Press Release) Human Genome Sciences Presents Interim Results of Phase 2b Trial of Albuferon with Ribavirin in Treatment-Naive Patients with Chronic Hepatitis C. May 1, 2006. (3) Zeuzem S, Benhamou Y, Shouval D, McHutchison J, Subramanian M, et al. Interim (week 12) Phase 2b virological efficacy and safety results of albumin interferon alfa-2b combined with ribavirin in genotype 1 chronic hepatitis C infection. 41st Annual Meeting of the European Association for the Study of the Liver (EASL), Vienna. Oral presentation #3088. (4) 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. (5) 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. (6) (HGSI Press Release) Human Genome Sciences Reports Interim Results of Phase 2 Clinical Trial of Albuferon in Combination with Ribavirin in Treatment-Experienced Hepatitis C Patients. November 15, 2005. (7) Bain VG, Kaita KD, Yoshida EM, McHutchison JG, Subramanian GM, et al. A Phase 2 study to assess the antiviral activity, safety, and pharmacokinetics of recombinant human albumin-interferon alfa fusion protein in genotype 1 chronic hepatitis C patients. Journal of Hepatology (2006). (8) (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. (9) 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). April 14, 2005. Abstract #447. (10) Balan V, Nelson DR, Sulkowski MS, Subramanian GM, et al. A Phase I/II study evaluating escalating doses of recombinant human albumin- interferon-alfa fusion protein in chronic hepatitis C patients who have failed previous interferon-alfa-based therapy. Antiviral Therapy, 11:35-45. (11) (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. (12) 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. October 25, 2003.
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