>> Human Genome Sciences Reports Positive Interim Quality-of-Life Data From Phase 2B Trial of Albuferon(TM) with Ribavirin in Treatment-Naive Hepatitis C Patients
Monday October 16, 7:00 am ET
- Albuferon associated with fewer missed work days and better patient-reported quality-of-life scores than pegylated interferon through Week 12 -
ROCKVILLE, Md., Oct. 16 /PRNewswire-FirstCall/ -- Human Genome Sciences, Inc. (Nasdaq: HGSI ) today reported 12-week interim quality-of-life results from a Phase 2b clinical trial to evaluate the efficacy, safety and impact on health-related quality of life of Albuferon(TM) in combination with ribavirin in patients with genotype 1 chronic hepatitis C (HCV) who are naive to interferon alpha-based treatment regimens. The interim results demonstrate that all Albuferon treatment groups consistently performed favorably through Week 12 compared to the pegylated interferon alpha treatment group, based on patient-reported disability days and health-related quality of life as measured by the SF-36 health survey. The data were presented over this past weekend at the annual Australian Gastroenterology Week in Adelaide.
"Health-related quality-of-life issues, including lost days of work and normal activity, pose a significant challenge for patients undergoing treatment for chronic hepatitis C," said Stephen Pianko, M.D., F.R.A.C.P., Ph.D., Associate Professor of Medicine, Monash University (Melbourne, Australia). "Interim results of the current study suggest that Albuferon may have the potential to offer a therapeutic alternative with less impairment of health-related quality of life, and fewer disability days, compared with the current standard of care, with at least comparable safety and efficacy. We look forward to continuing the evaluation of Albuferon to determine its appropriate role in the treatment of hepatitis C."
"Through Week 12 of the Phase 2b study, patients in the Albuferon treatment groups recorded fewer missed work days and, based on the SF-36 health assessment, reported better quality of life than patients in the pegylated interferon treatment group," said David C. Stump, M.D., Executive Vice President, Drug Development, HGS. "This result was observed in both the physical and mental component summary measures, as well as in the 8 individual domain scores. The SF-36 results in mental health suggest significantly less impairment of psychological well-being across the Albuferon treatment groups."
About the Albuferon Phase 2B 12-Week Quality-of-Life Results
Albuferon treatment groups recorded fewer disability days and reported less impairment of health-related quality of life through Week 12 of the Phase 2b study than patients in the pegylated interferon treatment group. The 900- mcg Albuferon dose administered at two-week intervals was associated with 75% fewer disability days, and the 1200-mcg Albuferon doses administered at two- week and four-week intervals were associated with 25% fewer disability days. Through Week 12, based on the SF-36 health assessment, patient-reported outcomes showed that the Albuferon treatment groups consistently performed favorably compared to PEGASYS in both the physical and mental component summary measures and in the 8 individual domain scores. SF-36 results in the mental health domain demonstrated significantly less impairment of psychological well-being across the Albuferon treatment groups (p=0.002 vs. PEGASYS). Of the four treatment arms in the Phase 2b study, the 900-mcg Albuferon dose administered once every two weeks was significantly associated with the least negative impact on mental and physical function, bodily pain, vitality, social functioning, and mental health domains, while maintaining efficacy and safety at least comparable to pegylated interferon alpha. Less worsening of health-related quality of life also was observed in the treatment arms receiving 1200-mcg Albuferon doses administered at two-week and four-week intervals, respectively, compared to the pegylated interferon alpha treatment group, with clinically meaningful differences observed in bodily pain, mental health and social functioning.
Health-related quality of life was assessed using the Short Form 36 (SF-36) health survey. SF-36 is a patient-reported outcomes instrument, consisting of 36 questions used to measure the health status of patients with chronic hepatitis C. The 36 questions result in an 8-scale health profile including: physical function, physical role limitations, vitality, general health perceptions, pain, social function, emotional role limitations, and mental health. Summaries of the combined physical and mental component measures were also used in the assessment.
About the Albuferon Phase 2B Trial Design
Data are available through Week 12 on 458 patients 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 were enrolled and randomized into four treatment groups, three of which receive subcutaneously administered Albuferon (900 mcg at two-week intervals, 1200 mcg at two-week intervals, and 1200 mcg at four-week intervals). The fourth treatment group serves as the active control group and receives 180-mcg doses of subcutaneously administered peginterferon alfa-2a (PEGASYS) once every week. All patients receive oral daily ribavirin. The primary efficacy endpoint of the Phase 2b study is sustained virologic response (SVR), defined as undetectable virus 24 weeks after completion of 48 weeks of treatment. The secondary endpoints include early virologic response at Week 12 (EVR12), and safety and health-related quality of life at Weeks 12, 24 and 48.
About Albuferon
Albuferon is a novel, long-acting form of interferon alpha, which was created by HGS using the Company's proprietary albumin fusion technology. This technology enables scientists to improve the pharmacological properties of therapeutic proteins by fusing the gene that expresses human albumin to the gene that expresses the active protein. Albuferon results from the genetic fusion of human albumin and interferon alpha 2b. Recombinant interferon alpha is approved for the treatment of hepatitis C, hepatitis B and a broad range of cancers.
Albuferon is being developed by HGS and Novartis under an exclusive worldwide development and commercialization agreement entered into in June 2006. <<
Human Genome Sciences Announces Positive Final Results of Phase 2b Trial of Albuferon
[Clinical results are not automatically positive just because a PR says so, and I would characterize these data as middling. Of course, Albuferon is already in two large phase-3 trials, which will determine the approvability and commercial prospects. The phase-2b trial reported here tested three different Albuferon dosing regimens vs Pegasys: 900mcg biweekly, 1200mcg biweekly, and 1200mcg monthly. In phase-3, HGSI is testing only the biweekly regimens and is separately working, with partner NVS, to define the dosing needed for efficacious monthly administration. (1200mcg monthly was too little.)
A prior quiz on this board is apropos to evaluating these data: please see #msg-13824566.]
- Albuferon 900-mcg dosed every two weeks achieved an SVR rate at least comparable to Pegasys dosed every week (ITT analysis), with more favorable quality-of-life scores -
- Efficacy was enhanced with all Albuferon doses vs. Pegasys in heavier treatment-adherent patients -
- Encouraging results for monthly dosing regimen -
ROCKVILLE, Md., June 7 /PRNewswire-FirstCall/ -- Human Genome Sciences, Inc. (Nasdaq: HGSI ) today announced the top-line final results of a Phase 2b clinical trial of Albuferon® (albinterferon alfa-2b) in combination with ribavirin in treatment-naive patients with genotype 1 chronic hepatitis C. The Company expects to make a full presentation of the final results at an appropriate scientific meeting later in 2007.
The final Phase 2b results confirm and extend the findings of several studies, which suggest that Albuferon may offer efficacy at least comparable to peginterferon alfa-2a, with half the injections and possibly less impairment of quality of life," said John McHutchison, M.D., Coordinating Center Principal Investigator for the Phase 2b trial, and Professor of Medicine and Associate Director, Duke Clinical Research Institute and Duke University Medical Center, Durham, North Carolina. "We are extremely pleased with the high quality of the data that have emerged from the Phase 2b study, and we look forward to continuing the evaluation of the 900-mcg and 1200-mcg doses of Albuferon in larger populations in Phase 3 trials."
The primary efficacy endpoint of the Phase 2b trial of Albuferon was sustained virologic response (SVR), defined as undetectable viral load (HCV RNA<10 IU/mL) at 24 weeks following completion of therapy. The final results demonstrated that Albuferon provided at least comparable efficacy vs. Pegasys (peginterferon alfa-2a), based on an ITT analysis. 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 (ITT analysis). This Albuferon treatment group also had more favorable health- related quality-of-life scores than the Pegasys treatment group. 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.
Top-Line Final Results by Treatment Group
The top-line final results of the Phase 2b trial at Week 24 following the completion of therapy include the following SVR rates and other findings:
Albuferon 900-mcg Every Two Weeks (Albuferon 900 Q2w)
-- Based on an intention-to-treat (ITT) analysis, 58.5% of patients in the Albuferon 900 Q2w treatment group achieved SVR, vs. 57.9% for Pegasys administered every week.
-- In heavier patients (>75 kg) who were treatment-adherent, 74.2% of those in the Albuferon 900 Q2w treatment group achieved SVR, versus 53.3% for Pegasys.
-- Among all treatment-adherent patients in the Albuferon 900 Q2w treatment group, 72.3% achieved SVR, versus 66.7% for Pegasys.
-- Based on the SF-36 Health Survey, patients in the Albuferon 900 Q2w treatment group reported less impairment of health-related quality of life, compared with patients in the Pegasys treatment group, as measured by both physical component and mental component SF-36 summary measures at all time-points throughout the 48-week treatment period.
-- 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 at Weeks 12 and 24, vs. the Pegasys group (Week 12: 3.0% for Albuferon 900 Q2w vs. 19.2% for Pegasys; Week 24: 5.8% for Albuferon 900 Q2w, vs. 22.4% for Pegasys).
-- The rate of discontinuations due to adverse events was 9.3% in the Albuferon 900 Q2w treatment group, vs. 6.1% in the Pegasys group.
"The 900-mcg Albuferon dose has the potential to offer patients an attractive therapeutic option, requiring half as many injections as Pegasys, with more favorable quality of life effects and favorable sustained virologic response data," said David C. Stump, M.D., Executive Vice President, Research and Development, HGS.
Albuferon 1200-mcg Every Two Weeks (Albuferon 1200 Q2w)
-- ITT analysis shows that 55.5% of patients in the Albuferon 1200 Q2w treatment group achieved SVR, vs. 57.9% for Pegasys administered every week.
-- In heavier patients (>75 kg) who were treatment-adherent, 67.9% of those in the Albuferon 1200 Q2w treatment group achieved SVR, versus 53.3% for Pegasys every week.
-- Among all treatment-adherent patients in the Albuferon 1200 Q2w treatment group, 70.6% achieved SVR, versus 66.7% for Pegasys.
-- ITT analysis shows that the Albuferon 1200 Q2w treatment group exhibited a robust early antiviral response (reduction in hepatitis C RNA viral load to below the level of quantitation): 74.5% for Albuferon 1200 Q2w at Week 12, vs. 65.8% for Pegasys. The Albuferon 1200 Q2w treatment group also had the most rapid time to HCV RNA negativity.
-- The rate of discontinuations due to adverse events was 18.2% in the Albuferon 1200 Q2w treatment group, vs. 6.1% in the Pegasys group. Adverse events observed were those typically expected with interferon therapy. Dose reductions were attempted in only 30.0% of Albuferon subjects prior to discontinuation, versus 42.9% for Pegasys.
"In the Albuferon Phase 3 trials, we will strongly encourage titration of dose where necessary to ensure tolerability, reduce the rate of discontinuations, and maximize the therapeutic benefit of the robust early antiviral response offered by the 1200-microgram dose on a two-week administration schedule," said Dr. Stump.
Albuferon 1200-mcg Monthly (Albuferon 1200 Q4w)
-- ITT analysis shows that 50.9% of patients in the Albuferon 1200 Q4w treatment group achieved SVR, vs. 57.9% for Pegasys administered every week.
-- In heavier patients (>75 kg) who were treatment-adherent, 61.0% of those in the Albuferon 1200 Q4w treatment group achieved SVR, versus 53.3% for Pegasys administered once every week.
-- Among all treatment-adherent patients in the Albuferon 1200 Q4w treatment group, 62.0% achieved SVR, versus 66.7% for Pegasys.
-- The rate of discontinuations due to adverse events was 12.1% in the Albuferon 1200 Q4w treatment group, vs. 6.1% in the Pegasys group.
-- The number of patients experiencing severe hematologic adverse events was significantly lower in the Albuferon 1200 Q4w treatment group (10.3%, vs. 23.7% for Pegasys, p=0.006).
"We are encouraged that more than half of the patients achieved sustained virologic response in the treatment group receiving Albuferon 1200-mcg once every month," said Dr. Stump. "These data, along with emerging Phase 2 data for a monthly 1500-mcg dose, provide an excellent rationale for the study that we and our collaborator, Novartis, are currently planning to evaluate higher doses of Albuferon administered monthly."
The top-line final Phase 2b results include data through Week 24 following completion of 48 weeks of therapy. The open-label, multi-center, active- controlled, dose-ranging trial enrolled and randomized 458 patients with genotype 1 chronic hepatitis C. Patients were randomized into four treatment groups, three of which received subcutaneously administered Albuferon (900 mcg every two weeks, 1200 mcg every two weeks, and 1200 mcg every four weeks). The fourth treatment group served as the active control group and received 180 mcg of subcutaneously administered peginterferon alfa-2a (Pegasys) once a week. All patients received weight-based oral ribavirin daily. The study was conducted in Australia, Canada, Czech Republic, France, Germany, Israel, Poland and Romania.
About Albuferon
Albuferon is a novel long-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 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. Recombinant interferon alpha is approved for the treatment of hepatitis C, hepatitis B and a broad range of cancers.
Albuferon is being developed by HGS and Novartis under an exclusive worldwide development and commercialization agreement entered into in June 2006. 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. Clinical development, commercial milestone and other payments to HGS could total as much as $507.5 million, including $92.5 million received to date. <<
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