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Albuferon-Alpha (Albumin-Interferon Alpha)
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....The data also demonstrate that Albuferon remained in the blood substantially longer than is reported for recombinant interferon alpha and pegylated interferon alpha. Albuferon was detectable for up to four weeks following the second subcutaneous injection.....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.....
At the end of this report are details of study data reported at AASLD Nov 2005.
Background
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 company's proprietary albumin fusion technology. Human Genome Sciences is developing Albuferon as a potential treatment for chronic hepatitis C. Clinical and preclinical results to date suggest that Albuferon is well tolerated, remains in the blood substantially longer than is reported for recombinant interferon alpha and pegylated interferon alpha, and exhibits robust antiviral activity.1-8
Molecular Model of Albuferon TM
Figure 1. Albuferon is a single polypeptide molecule that combines the therapeutic activity of interferon alpha with the long half-life of human serum albumin (HSA).
Clinical Progress
Albuferon is in Phase 2 clinical development for the treatment of chronic hepatitis C.
Phase 2 Study in Treatment-Naïve Patients: In April 2005, Human Genome Sciences reported the results of a Phase 2 clinical trial in patients with chronic hepatitis C who are naïve to interferon-alpha treatments.1-2 The results demonstrate that Albuferon was well tolerated, had a prolonged half-life, and exhibited robust antiviral activity, with reductions in hepatitis C viral load at dose-dependent magnitude and durability.
The Phase 2 trial, which was conducted in Canada, was a randomized, open-label, multi-center, parallel-design, dose-ranging study to evaluate the safety, tolerability, pharmacology and optimal dosing of Albuferon.3, 9 A total of 56 patients were enrolled in the trial and randomized to five dose groups (200 mcg, 450 mcg, 670 mcg, 900 mcg and 1200 mcg).10 Patients were given two doses of Albuferon monotherapy administered subcutaneously fourteen days apart and were followed for safety and antiviral evaluations for a total of 6 weeks. The pharmacodynamic activity of Albuferon was evaluated based on hepatitis C (HCV) RNA viral load reductions over a 42-day period of exposure. One of the study objectives was to identify a range of active doses that Human Genome Sciences plans to evaluate in a larger 48-week study of Albuferon in combination with ribavirin in patients with HCV genotype 1 who are naïve to interferon treatments.
The primary efficacy endpoint of the Phase 2 study in interferon-naïve patients was the rate of virologic response at Day 28, defined as at least a 2-log reduction in HCV viral load compared with baseline, or undetectable HCV viral load. The data presented show 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 in treatment with the pegylated interferons.11 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.12
The data also demonstrate that Albuferon remained in the blood substantially longer than is reported for recombinant interferon alpha and pegylated interferon alpha. Albuferon was detectable for up to four weeks following the second subcutaneous injection. The Cmax (peak drug level) increased in a linear manner over the dose range evaluated (200-1200 mcg). Albuferon exhibited a median half-life of 148 hours, supporting dosing at intervals of 2-4 weeks. This compares to a reported mean elimination half-life of 80 hours (50-140 hours) for Pegasys and 40 hours (22-60 hours) for PEG-Intron.13-14
Results of the Phase 2 study in interferon-naïve patients demonstrate that Albuferon was well tolerated with adverse events that were transient and mostly mild to moderate in severity. One serious adverse event was reported (acute colitis) and has subsequently resolved. There were no discontinuations due to reductions in hematologic cell counts. No subjects developed newly emergent antibodies to alpha interferon. One subject developed antibodies to human serum albumin. There was no apparent correlation between the emergence of antibodies and adverse events, antiviral response or pharmacokinetics.
Figure 2. Results of the P hase 2 study of Albuferon in treatment-naïve patients demonstrate that Albuferon was detectable in the blood for up to four weeks following the second subcutaneous injection – substantially longer than is reported for the pegylated interferons. The peak drug level increased in a linear manner over the dose range evaluated (200-1200 mcg). Albuferon exhibited a median half-life of 148 hours, supporting dosing at intervals of 2-4 weeks.
Phase 2 Study in Combination with Ribavirin in Treatment-Experienced Patients: In November 2004, Human Genome Sciences began dosing patients in a Phase 2 clinical trial of Albuferon in combination with ribavirin to evaluate the safety, tolerability and efficacy of Albuferon in patients with chronic hepatitis C who failed to respond to previous interferon alpha-based treatment regimens.15 The trial is a randomized, open-label, multi-center, dose-escalation study. It is being conducted in the United States, and will enroll up to 100 patients with chronic hepatitis C who have failed to respond to treatment(s) with any interferon-alpha product. 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. Patients are being randomized into 3-4 dose groups, and are receiving Albuferon administered subcutaneously either 14 or 28 days apart. All patients are receiving weight-based oral daily ribavirin 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 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 ribavirin. The primary efficacy endpoint of the study is sustained virologic response, defined as undetectable virus at 24 weeks after the end of therapy. Preliminary eight-week data from the ongoing trial are available.3 The preliminary data show that Albuferon administered at 2-week or 4-week intervals in combination with ribavirin was safe, well tolerated, and demonstrated antiviral activity in all treatment groups for which data are available.
Phase 1/2 Study in Treatment-Experienced Patients: The results of a Phase 1/2 clinical trial of Albuferon in interferon alpha-experienced adults with chronic hepatitis C were presented at the November 2004 Annual Meeting of the American Association for the Study of Liver Diseases (AASLD).4-5 Data presented on 119 patients demonstrate that Albuferon was well tolerated, exhibited a prolonged half-life, was biologically active and able to reduce viral load with dose-dependent magnitude and durability. On average, patients participating in the Phase 1/2 clinical trial had been treated previously for approximately 63 weeks with interferon alpha-containing regimens. Ninety-two percent of the patients (110/119) were infected with hepatitis C virus genotype 1, which accounts for nearly seventy percent of all HCV infections in North America. Patients were treated with one or two doses of Albuferon administered subcutaneously 14 days apart. Doses administered ranged from 7-900 mcg. The Phase 1/2 clinical trial results show that Albuferon was well tolerated, with adverse events that were mostly transient and mild to moderate in severity, and with no discontinuations due to adverse events or reductions in hematologic cell counts. Preliminary immunogenicity data presented at the AASLD meeting show that Albuferon immunogenicity occurred at rates consistent with those reported for other interferon alpha-based therapies, with no apparent correlation between the emergence of Albuferon antibodies and adverse events, antiviral response or pharmacokinetics. The vast majority of Albuferon antibody titers were low (<100 ng/mL). Viral load levels represent the quantity of hepatitis C virus in the blood and are a marker for drug activity. Forty-seven percent of Albuferon-treated patients in the combined single-dose and two-dose cohorts at doses of 120-900 mcg experienced an antiviral response, as demonstrated by reductions in viral load of 1.0 log or greater. The data presented show that both magnitude and duration of early anti-viral response were dose-dependent.
How Albuferon Works
The mechanism of action of Albuferon is expected to be similar to that of interferon alpha. Interferons belong to a family of proteins known as cytokines that occur naturally in the human body. Cytokines control cellular processes, such as cell growth, activation, migration and aging. While the precise mechanism of action for interferon alpha is not known, research has demonstrated direct antiviral activity in patients with diseases like hepatitis C, as well as immune-modulating and direct antitumor effects in certain types of cancer.16-17
Preclinical and clinical results to date suggest that Albuferon induces a biological effect similar to that induced by currently available recombinant interferon alpha treatments. Microarray gene expression data show that Albuferon up-regulates the same 31 genes as recombinant interferon alpha in a dose-dependent manner. Microarray gene expression data also demonstrate that Albuferon in treatment-experienced patients induces interferon-specific gene expression patterns consistent with those observed in patients receiving pegylated interferon alpha and ribavirin.6-7
Potential Treatment Settings
Human Genome Sciences is currently developing Albuferon as a potential treatment for chronic hepatitis C. Albuferon also has the potential to treat a broad range of cancers. Hepatitis C is an inflammation of the liver caused by the hepatitis C virus. Hepatitis C infection is currently the most common chronic blood-borne infection in the U.S., afflicting four times as many people as are afflicted with HIV, the virus that causes AIDS. The hepatitis C virus is transmitted primarily through significant or repeated exposures to infected blood. In the United States, 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 with chronic hepatitis C.18
Approximately four million people in the United States are infected with the hepatitis C virus, and between sixty and eight-five percent of hepatitis C-infected people develop chronic hepatitis C. A four-fold increase in the number of adults diagnosed with chronic hepatitis C is projected from 1990 to 2015. The current standard of care for treating chronic hepatitis C is combination therapy consisting of pegylated interferon alpha and ribavirin, an antiviral drug.18
Human Genome Sciences believes that Albuferon may provide patients with similar or improved efficacy, with the potential for superior safety and an administration schedule with less frequent dosing than currently available treatments.
How Albuferon Was Created
Albuferon was created using Human Genome Sciences' proprietary albumin fusion technology. Albumin fusion technology allows scientists to create next-generation protein drugs by fusing the gene that expresses human albumin to the gene that expresses a therapeutically active protein. Albuferon results from the genetic fusion of human albumin and interferon alpha.
Human albumin is the most prevalent naturally occurring blood protein in the human circulatory system, persisting in circulation in the body for over twenty days. Research has shown that genetic fusion of therapeutic proteins to human albumin decreases clearance and prolongs the half-life of the proteins.
Footnotes
1. Bain V, et al. A Phase 2 study to assess antiviral response, safety, and pharmacokinetics of Albuferon in IFNa-naïve 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).
2. (HGSI Press Release) Human Genome Sciences Reports Positive Results of Phase 2 Clinical Trial of Albuferon in Treatment-Naïve Patients with Chronic Hepatitis C. April 14, 2005.
3. (HGSI Press Release) Human Genome Sciences Completes Enrollment in a Phase 2 Clinical Trial of Albuferon in Treatment-Naïve Patients with Chronic Hepatitis C. February 16, 2005.
4. Balan V, et al. Albuferon -- 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).
5. (HGSI Press Release) Human Genome Sciences Reports Positive Results of Phase 1/2 Clinical Trial of Albuferon in Chronic Hepatitis C. November 2, 2004.
6. 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.
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. 40 th Annual Meeting of the European Association for the Study of the Liver (EASL), Paris. April 14, 2005. (Abstract #447).
8. 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.
9. (HGSI Press Release) Human Genome Sciences Initiates Phase 2 Clinical Trial of Albuferon for the Treatment of Chronic Hepatitis C. May 26, 2004.
10. It is important to note that the method of measurement for dose determination in the Phase 2 study of Albuferon in treatment-naïve patients is different from the method of measurement in the Phase 1/2 study of Albuferon. Accordingly, the 200 mcg dose in the current study is equivalent to a 150 mcg dose in the Phase 1/2 study, the 450 mcg dose is equivalent to 340 mcg in the prior study, and the 1200 mcg dose is equivalent to 900 mcg.
11. 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: Vol 36 No 4, Pt 2 of 2.
12. Di Bisceglie AM, Rustgi VK, Thuluvath P, et al. Pharmacokinetics and pharmacodynamics of pegylated interferon alfa-2a or alfa-2b with ribavirin in treatment naïve patients with genotype 1 chronic hepatitis C. Hepatology 2004;40,4;734a, abstract LB18.
13. PEGASYS® Physicians Desk Reference. (Last updated December 2003).
14. PEG-INTRON® Physicians Desk Reference. (Last updated September 2003).
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. Glue P, Fang JWS, Rouzier-Panis R, et al., Pegylated interferon-alpha 2b: Pharmacokinetics, Pharmacodynamics, Safety and Preliminary Efficacy Data. Clinical Pharm Ther 2000; 68:556-567.
17. Perry CM, Jarvis B., Peginterferon-alpha-2a (40 kD): A Review of Its Use in the Management of Chronic Hepatitis C. Drugs 2001; 61:2263-2288.
18. 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.
Bibliography
Bain V, et al. A Phase 2 study to assess antiviral response, safety, and pharmacokinetics of Albuferon in IFNa -naïve 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).
Balan V, et al. Albuferon -- 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).
Balan V, et al. A Phase 1/2 study to evaluate the pharmacokinetics, safety, tolerability, immunogenicity, and pharmacodynamics of Albuferon-alpha in treatment experienced subjects with chronic hepatitis C. 54th Annual Meeting of the American Association for the Study of Liver Diseases, Boston. October 25, 2003.
Balan V., et al. Molecular profiles of drug response in HCV infected patients during the first 4 weeks of therapy for chronic hepatitis C virus with pegylated interferon containing regimens or Albuferon-alpha. 54th Annual Meeting of the American Association for the Study of Liver Diseases, Boston. October 27, 2003.
Davis G, Balan V, et al. A Phase 1 study to evaluate the pharmacokinetics, safety, and tolerability of escalating doses of a novel recombinant human albumin-interferon alpha fusion protein (Albuferon) in subjects with chronic hepatitis C. 2002 November 1-5, 53rd Annual Meeting of the American Association for the Study of Liver Diseases.
Di Bisceglie AM, Rustgi VK, Thuluvath P, et al. Pharmacokinetics and pharmacodynamics of pegylated interferon alfa-2a or alfa-2b with ribavirin in treatment naïve patients with genotype 1 chronic hepatitis C. Hepatology 2004;40,4;734a, abstract LB18.
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).
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.
Osborn B, Murray J, Olsen H, and Nardelli B. Pharmacokinetics and pharmacodynamics of Albuferon in cynomolgus monkeys. 2002 April 26-28, American Association for the Study of Liver Diseases HCV Conference.
HUMAN GENOME SCIENCES REPORTS INTERIM RESULTS OF PHASE 2 CLINICAL TRIAL OF ALBUFERON IN COMBINATION WITH RIBAVIRIN IN TREATMENT-EXPERIENCED HEPATITIS C PATIENTS
Company press release
ROCKVILLE, Maryland – November 15, 2005 – Human Genome Sciences, Inc. (Nasdaq: HGSI) today announced the interim results of a Phase 2 clinical trial to evaluate the safety, tolerability and efficacy of Albuferon (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.
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 date3-11, 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-naïve patients with genotype 1 chronic hepatitis C were presented in April 2005 at the 40 th 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 > 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 naïve 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.
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