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Albuferon® (albinterferon alfa-2b)

Albuferon® is a novel longer-acting form of interferon alpha created by HGS using its proprietary albumin fusion technology. 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 approximately 19 days. Research shows that genetic fusion of therapeutic proteins to human albumin decreases clearance and prolongs the half-life of the therapeutic proteins. Recombinant interferon alpha is approved for the treatment of hepatitis C, hepatitis B and a number of cancers

How Albuferon Works

Albuferon appears to induce a biological effect similar to that induced by currently available recombinant interferon alpha treatments. Microarray gene expression data show that Albuferon up-regulates, or increases the activity of, the same 31 genes that recombinant interferon alpha up-regulates in a dose-dependent manner.[1-2] The 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 that interferon alpha has direct antiviral activity in patients with diseases such as hepatitis C, as well as immune-modulating and direct antitumor effects in certain types of cancer.[3-5]

Phase 2 clinical results to date suggest that Albuferon could offer hepatitis C patients a therapeutic option requiring half as many injections as Pegasys (peginterferon alfa-2a), with comparable efficacy and safety, and with the potential for less impairment of health-related quality of life and fewer lost days of work while on treatment.[6-31]

Molecular Model of Albuferon

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.


Collaboration with Novartis for Development and
Commercialization of Albuferon

In June 2006, HGS entered into an exclusive worldwide agreement with Novartis for the co-development and commercialization of Albuferon.[32-33] Novartis is a global leader in the pharmaceutical industry and has demonstrated its commitment to leadership in infectious diseases. HGS and Novartis are working closely together to advance Albuferon to the market.

Under the agreement, HGS and Novartis will co-commercialize Albuferon in the United States, and will share clinical development costs, U.S. commercialization costs and U.S. profits equally. Novartis will be responsible for commercialization in the rest of the world and will pay HGS a royalty on those sales. HGS will have primary responsibility for the bulk manufacture of Albuferon, and Novartis will have responsibility for commercial manufacturing of the finished drug product. Clinical development, commercial milestone and other payments to HGS could total as much as $507.5 million, including $132.5 million received to date.

Potential Treatment Settings

HGS and Novartis are currently developing Albuferon as a potential treatment for chronic hepatitis C. Hepatitis C 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.[34] It is estimated that approximately 170 million people worldwide are infected with the hepatitis C virus, including approximately four million people in the United States. The hepatitis C virus can cause serious liver disease in a significant proportion of people who are infected, leading to cirrhosis, primary liver cancer and even death

When detectable levels of the virus persist in the blood for at least six months, a person is diagnosed as having chronic hepatitis C. Between 60% and 85% of people infected with hepatitis C develop chronic hepatitis C. The current standard of care is a combination of pegylated interferon alpha and ribavirin, an antiviral drug.[3-4]

HGS believes that Albuferon could become the market-leading interferon in treatment regimens for chronic hepatitis C, assuming success in ongoing Phase 3 trials. Albuferon requires half the injections required by the pegylated interferons, and Phase 2 results demonstrated that Albuferon may offer at least comparable efficacy, comparable safety, and the potential for less impairment of health-related quality of life and daily activity on treatment.

Albuferon Pharmacokinetics

Figure 2.  Results of a Phase 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.


Phase 3 Clinical Development Program

The Albuferon Phase 3 clinical development program includes two randomized, open-label, active-controlled, multi-center, non-inferiority trials to evaluate the efficacy, safety and impact on health-related quality of life of Albuferon in combination with ribavirin, versus Pegasys (peginterferon alfa-2a) in combination with ribavirin. HGS designed the Phase 3 program for Albuferon in collaboration with Novartis and leading international experts in hepatitis C. The Company also reviewed the trial designs with U.S. and key European regulatory authorities and received their positive feedback.

HGS completed enrollment ahead of schedule in both of the Albuferon Phase 3 trials: ACHIEVE 1 in treatment-naïve patients with chronic hepatitis C genotype 1 and ACHIEVE 2/3 in treatment-naïve patients with chronic hepatitis C genotype 2 or 3.[35-36] As a result of the early completion of enrollment, HGS now expects to have Phase 3 data available in the spring of 2009, with filing of global marketing authorization applications anticipated in the fall of 2009.[37-38]  

ACHIEVE 1 enrolled a total of 1331 patients at 150 clinical sites in 12 countries. Patients were randomized into three treatment groups, including two groups receiving subcutaneously administered Albuferon once every two weeks (900 mcg or 1200 mcg), and an active control group receiving Pegasys once every week at the standard dose of 180 mcg. In January 2008, HGS announced modified dosing in one arm of each of the ACHIEVE trials. Patients who had been receiving the 1200-mcg dose have now been moved to the 900-mcg dose. The change was based on recommendations made by the studies’ independent Data Monitoring Committee (DMC).[39] All patients receive daily oral ribavirin concomitantly. The total duration of therapy will be 48 weeks, with 24 weeks of follow-up. The primary efficacy endpoint is sustained virologic response (SVR), defined as undetectable HCV RNA (< 10 IU/mL) at Week 72.

ACHIEVE 2/3 enrolled a total of 933 patients into three treatment groups, which will receive the same doses of Albuferon and Pegasys administered on the same schedules as ACHIEVE 1, with concomitant daily administration of oral ribavirin. The total duration of therapy will be 24 weeks, with 24 weeks of follow-up. The primary efficacy endpoint is SVR, defined as undetectable HCV RNA at Week 48.

Clinical Progress

In November 2007, HGS announced the presentation of final results in a Phase 2b clinical trial of Albuferon in patients with genotype 1 chronic hepatitis C who were naïve to interferon alpha-based treatment regimens.[6-9} Albuferon requires half as many injections as Pegasys (peginterferon alfa-2a), and the Phase 2b results demonstrated that Albuferon provided at least comparable efficacy vs. Pegasys, with comparable safety, less impairment of health-related quality of life on treatment and fewer lost days of work.

The treatment group receiving Albuferon 900-mcg doses every two weeks achieved an SVR rate of 58.5%, vs. 57.9% for the group receiving Pegasys once every week. This Albuferon treatment group also had more favorable health-related quality-of-life scores than the Pegasys treatment group, and significantly fewer working patients in the Albuferon 900 Q2w treatment group reported missing 7 days or more of work during the month prior to their visits. Among heavier patients (>75 kg) who were treatment-adherent, 71.2% of those in the combined groups receiving Albuferon every two weeks achieved SVR, versus 53.3% for patients receiving Pegasys once a week. The ability to maintain efficacy in heavier patients is of particular importance in certain markets, including the United States, where a large percentage of patients weigh more than 75 kg.

The Phase 2b results also support further evaluation of Albuferon with monthly dosing. Higher doses of Albuferon administered every four weeks, in combination with ribavirin, will be explored in a separate Phase 2b trial conducted by Novartis, which is expected to begin by year-end 2007.

In November 2007, HGS announced the presentation of final results in a Phase 2 study in patients with genotype 1 chronic hepatitis C who did not respond to prior interferon alpha-based treatments.[10-11] The results demonstrated that Albuferon had an acceptable long-term safety profile at doses up to 1800 mcg every two weeks in these patients, and produced an overall sustained virologic response (SVR) rate of 17%. The SVR rate was 11% in the important and most difficult-to-treat subgroup of genotype 1 hepatitis C patients who failed to respond to previous treatment with a combination of pegylated interferon and ribavirin. These SVR results are in line with previous studies of long-acting interferons in non-responders, with less frequent dosing.

How Albuferon Was Created

Albuferon was created using HGS’ 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 approximately 19 days. Research has shown that genetic fusion of therapeutic proteins to human albumin decreases clearance and prolongs the half-life of the therapeutic proteins.[40, 41]

For More Information about Albuferon Clinical Trials

Health professionals and patients interested in clinical trials of Albuferon or other HGS products may inquire by e-mailing This e-mail address is being protected from spam bots, you need JavaScript enabled to view it or calling HGS at (301) 610-5790, extension 3550.

Footnotes

  1. 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.  April 14, 2005.  (Abstract #447).
  2. 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. 
  3. 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.
  4. Perry CM, Jarvis B, et al.  Peginterferon-alpha-2a (40 kD): a review of its use in the management of chronic hepatitis C.  Drugs 2001; 61:2263-2288.
  5. 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.
  6. (HGSI Press Release) Human Genome Sciences Announces Presentation at AASLD of Results of Phase 2b Trial of Albuferon for Chronic Hepatitis C.  November 5, 2007.
  7. Zeuzem S, Yoshida E, Benhamou Y, McHutchison J, et al.  Sustained virologic response with albinterferon alfa-2b plus ribavirin treatment in IFN-naive, chronic hepatitis C genotype 1 patients.  Oral presentation.  58th Annual Meeting of the American Association for the Study of Liver Diseases.  November 6, 2007.
  8. (HGSI Press Release) Human Genome Sciences Announces Full Presentation of Quality-of-Life Results from Phase 2b Trial of Albuferon for Hepatitis C.  November 5, 2007.
  9. Pianko S, Yoshida E, Zeuzem S, Subramanian M, et al.  Favorable quality of life (QOL) with albinterferon alfa-2b plus ribavirin in genotype 1, IFN treatment-naive, chronic hepatitis C patients.  58th Annual Meeting of the American Association for the Study of Liver Diseases.  November 6, 2007.
  10. (HGSI Press Release) Human Genome Sciences Presents Results of Phase 2 Trial of Albuferon in Chronic Hepatitis C Patients Who Failed to Respond to Previous Therapy.  November 6, 2007.
  11. Nelson D, Rustgi V, Balan V, Subramanian M, et al.  Sustained virologic response with albinterferon alfa-2b plus ribavirin treatment in prior interferon therapy nonresponders.  Oral presentation.  58th Annual Meeting of the American Association for the Study of Liver Diseases.  November 4, 2007.
  12. (HGSI Press Release) Human Genome Sciences Announces Positive Final Results of Phase 2b Trial of Albuferon.  June 7, 2007.
  13. Zeuzem S, Benhamou Y, Bain VG, McHutchison J, et al.  Antiviral response at week 12 following completion of treatment with albinterferon alfa-2b plus ribavirin in genotype 1, IFN-naïve, chronic hepatitis C patients.  42nd Annual Meeting of the European Association for the Study of the Liver (EASL).  Oral presentation.  April 14, 2007.
  14. Bain VG, Marotta P, Kaita K, Subramanian M, et al.  Comparable antiviral response rates with albinterferon alfa-2b dosed at Q2W or Q4W intervals in naïve subjects with genotypes 2 or 3 chronic hepatitis C.  42nd Annual Meeting of the European Association for the Study of the Liver (EASL).  Oral presentation.  April 12, 2007.
  15. Neumann AU, Rozenberg L, Zeuzem S, Subramanian M, et al.  Albinterferon alfa-2b dosed at Q2W or Q4W intervals demonstrates comparable week 12 antiviral response in IFN-naïve, genotype 1 rapid viral responders.  42nd Annual Meeting of the European Association for the Study of the Liver (EASL).  Poster presentation.  April 12, 2007. 
  16. (HGSI Press Release) Human Genome Sciences Reports Positive Interim Results of Phase 2b Trial of Albuferon.  April 14, 2007.
  17. Nelson D, Rustgi V, Balan V, Subramanian M, et al.  Sustained virologic response rates with albumin interferon alfa-2b in combination with ribavirin in non-responders to prior interferon therapy:  interim results from a Phase 2 study.  57th Annual Meeting of the American Association for the Study of Liver Diseases.  October 31, 2006.  Poster presentation #1136.
  18. McHutchison J, Zeuzem S, Benhamou Y, and Subramanian M.  Interim antiviral and safety data with albumin interferon alfa-2b combined with ribavirin in a Phase 2b study conducted in a genotype 1, IFN-naïve, chronic hepatitis C population.  57th Annual Meeting of the American Association for the Study of Liver Diseases.  October 31, 2006.  Poster presentation #1141.
  19. Fiscella M, Balan V, Nelson D, and Corey A.  Favorable pharmacokinetic of albumin interferon alfa-2b in subjects with chronic hepatitis C.  57th Annual Meeting of the American Association for the Study of Liver Diseases.  October 31, 2006.  Poster presentation #1140.
  20. (HGSI Press Release) Human Genome Sciences Reports Positive Interim Results of Phase 2 Trials of Albuferon with Ribavirin in Patients with Chronic Hepatitis C.  October 31, 2006.
  21. Pianko S, Sievert W, McHutchison J, Subramanian M, et al.  Favorable quality of life (QOL) in the first 12 weeks of treatment with albumin interferon alfa-2b compared with PEG-IFN in a Phase 2b study conducted in genotype 1, IFN-naïve, chronic hepatitis C subjects.  Poster presentation.  Australian Gastroenterology Week, October 14, 2006.  
  22. (HGSI Press Release) Human Genome Sciences Reports Positive Interim Quality-of-Life Data from Phase 2b Trial of Albuferon with Ribavirin in Treatment-Naïve Hepatitis C Patients.  October 16, 2006.
  23. 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. Oral presentation #3088.
  24. (HGSI Press Release) Human Genome Sciences Presents Interim Results of Phase 2b Trial of Albuferon with Ribavirin in Treatment-Naïve Patients with Chronic Hepatitis C.  May 1, 2006.
  25. Rustgi V, Nelson D, Balan V, McHutchison J, Subramanian M, et al.  A Phase 2 dose-escalation study of albumin 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.  Oral Presentation #113.
  26. (HGSI Press Release) Human Genome Sciences Presents Interim Results of Phase 2 Trial of Albuferon with Ribavirin in Patients with Chronic Hepatitis C Who Failed to Respond to Prior Therapy.  May 1, 2006.
  27. Bain VG, Kaita KD, Yoshida EM, et al.  A Phase 2 study to evaluate the antiviral activity, safety, and pharmacokinetics of recombinant human albumin-interferon alfa fusion protein in genotype 1 chronic hepatitis C patients.  J Hepatol 2006 Apr; 44(4):671-8.  Epub 2006 Jan 30.
  28. (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.
  29. Balan V, Nelson DR, Sulkowski MS, et al.  A Phase 1/2 study evaluating escalating doses of recombinant human albumin-interferon alpha fusion protein in chronic hepatitis C patients who have failed previous interferon-alpha-based therapy.  Antivir Ther 2006; 11(1):35-45.
  30. (HGSI Press Release) Human Genome Sciences Reports Positive Results of Phase 1/2 Clinical Trial of Albuferon in Chronic Hepatitis C.  November 2, 2004.
  31. It is important to note that the method of measurement for dose determination in the Phase 2 studies of Albuferon is different from the method of measurement in the Phase 1/2 study of Albuferon.  Accordingly, the 900-mcg dose in the Phase 2 and Phase 3 studies 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.
  32. (HGSI Press Release) Human Genome Sciences Announces Collaboration with Novartis for Development and Commercialization of Albuferon.  June 6, 2006.
  33. (Novartis Press Release) Novartis Strengthens Infectious Diseases Portfolio by Acquiring Rights to Albuferon, a Novel Hepatitis C Interferon Compound Set to Enter Phase III Trials.  June 6, 2006.
  34. Alter MJ.  Epidemiology of hepatitis C in the West.  Semin Liver Dis 1995; 15:5-14.
  35. (HGSI Press Release) Human Genome Sciences Completes Patient Enrollment in Phase 3 Albuferon Trial Ahead of Schedule.  August 28, 2007.
  36. (HGSI Press Release) Human Genome Sciences Completes Enrollment Ahead of Schedule in Second Phase 3 Albuferon Trial.  November 1, 2007.
  37. (HGSI Press Release) Human genome Sciences Initiates Pivotal Phase 3 Clinical Trials of Albuferon.  December 19, 2006.
  38. (HGSI Press Release) Human Genome Sciences Announces Phase 3 Clinical Development Program for AlbuferonTM in Chronic Hepatitis C.  October 4, 2006.
  39. (HGSI Press Release) Human Genome Sciences Modifies Dosing in ACHIEVE Trials of Albuferon.  January 23, 2008.
  40. Subramanian GM, McHutchison JG, Zeuzem S, et al.  Albinterferon alfa-2b: a genetic fusion protein for the treatment of chronic hepatitis C.  Nature Biotechnology.  December 2007.
  41. Peters T. All about albumin. Academic Press, San Diego, CA. 1996.

  

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Bain VG, Kaita KD, Yoshida EM, et al. A Phase 2 study to evaluate the antiviral activity, safety, and pharmacokinetics of recombinant human albumin-interferon alfa fusion protein in genotype 1 chronic hepatitis C patients. J Hepatol 2006 Apr; 44(4):671-8. Epub 2006 Jan 30.

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To view announcements on Albuferon, click on the following:

Human Genome Sciences Modifies Dosing in ACHIEVE Trials of Albuferon - January 23, 2007

Human Genome Sciences Presents Results of Phase 2 Trial of Albuferon® in Chronic Hepatitis C Patients who Failed to Respond to Previous Therapy - November 5, 2007

Human Genome Sciences Announces Full Presentation of Quality-of-Life Results from Phase 2b Trial of Albuferon® for Hepatitis C - November 5, 2007

Human Genome Sciences Announces Presentation at AASLD of Results of Phase 2b Trial of Albuferon® for Chronic Hepatitis C - November 5, 2007

Human Genome Sciences Completes Enrollment Ahead Of Schedule In Second Phase 3 Albuferon® Trial - November 1, 2007

Human Genome Sciences Announces $40 Million Milestone Payment Related to Albuferon® Development - August 28, 2007

Human Genome Sciences Completes Enrollment of First Phase 3 Albuferon® Trial Ahead of Schedule - August 28, 2007

Human Genome Sciences Announces Positive Final Results of Phase 2b Trial of Albuferon® - June 7, 2007

Human Genome Sciences Reports Positive Interim Results Of Phase 2b Trial Of Albuferon® - April 14, 2007

Human Genome Sciences Initiates Phase 3 Clinical Trial of Albuferon® with Ribavirin in Treatment-Naïve Patients with Chronic Hepatitis C Genotypes 2 and 3 - February 27, 2007

Human Genome Sciences Announces Positive Interim Results of Phase 2b Trial of Albuferon® with Ribavirin in Treatment-Naïve Patients with Chronic Hepatitis C - February 27, 2007

Human Genome Sciences Initiates Phase 3 Clinical Trial of Albuferon® in Combination with Ribavirin in Treatment-Naïve Patients with Chronic Hepatitis C - December 19, 2006

Human Genome Sciences Reports Positive Interim Results of Phase 2 Trials of Albuferon™ with Ribavirin in Patients with Chronic Hepatitis C - October 31, 2006

Human Genome Sciences Reports Positive Interim Quality-of-Life Data from Phase 2b Trial of Albuferon™ With Ribavirin in Treatment-Naïve Hepatitis C Patients - October 16, 2006

Human Genome Sciences Announces Phase 3 Clinical Development Program for Albuferon™ in Chronic Hepatitis C - October 4, 2006

Human Genome Sciences Announces Collaboration with Novartis for Development and Commercialization of Albuferon™ - June 6, 2006

Human Genome Sciences Presents Interim Results Of Phase 2b Trial Of Albuferon™ With Ribavirin In Treatment-Naïve Patients With Chronic Hepatitis C - May 1, 2006

Human Genome Sciences Presents Interim Results Of Phase 2 Trial Of Albuferon™ With Ribavirin In Patients With Chronic Hepatitis C Who Failed To Respond To Previous Therapy - May 1, 2006

Human Genome Sciences Reports Interim Results of Phase 2 Trial of Albuferon™ in Combination with Ribavirin in Treatment-Experienced Patients with Chronic Hepatitis C - March 14, 2006

Human Genome Sciences Announces Interim Results of Phase 2B Clinical Trial of Albuferon™ in Combination with Ribavirin in Treatment-Naïve Patients with Chronic Hepatitis C - March 14, 2006

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

Human Genome Sciences Completes Patient Enrollment in a Phase 2B Clinical Trial of Albuferon™ in Combination with Ribavirin in Treatment-Naïve Patients with Chronic Hepatitis C - October 25, 2005

Human Genome Sciences Initiates Phase 2B Clinical Trial of Albuferon™ in Combination with Ribavirin in Treatment-Naïve Patients with Chronic Hepatitis C - June 1, 2005

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

Human Genome Sciences Reports Positive Results of Phase 2 Clinical Trial of Albuferon™ in Treatment-Naïve Patients with Chronic Hepatitis C - April 14, 2005

Human Genome Sciences Completes Enrollment in a Phase 2 Clinical Trial of Albuferon™ in Treatment-Naïve Patients with Chronic Hepatitis C - February 16, 2005

Human Genome Sciences Initiates Phase 2 Clinical Trial of Albuferon™ in Combination with Ribavirin in Treatment-Experienced Hepatitis C Patients - November 30, 2004

Human Genome Sciences Reports Positive Results of Phase 1/2 Clinical Trial of Albuferon™ in Chronic Hepatitis C - November 2, 2004

Human Genome Sciences Initiates Phase 2 Clinical Trial of Albuferon™ for the Treatment of Chronic Hepatitis C - May 26, 2004

Human Genome Sciences Reports Interim Results of Phase 1/2 Clinical Trial of Albuferon™ in Patients Infected With Hepatitis C Virus - October 28, 2003

Human Genome Sciences Reports Progress in Clinical Trials of Five Drugs at JP Morgan H&Q Conference - January 6, 2003

Interim Results of Phase 1 Albuferon™-Alpha Clinical Trial Demonstrate Safety, Prolonged Half-Life, and Biological Activity in Patients Infected With Hepatitis C Virus - November 4, 2002

 
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