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Albuferon vs Pegasys Phase 2B Study Results
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HUMAN GENOME SCIENCES ANNOUNCES POSITIVE INTERIM RESULTS OF PHASE 2B CLINICAL TRIAL OF ALBUFERON IN COMBINATION WITH RIBAVIRIN IN TREATMENT- NAiVE PATIENTS WITH CHRONIC HEPATITIS C
- Interim 12- week data suggest at least comparable antiviral activity versus Pegasys, with less frequent dosing -
- Conference call today at 10 AM Eastern -
ROCKVILLE, Maryland - March 14, 2006 - Human Genome Sciences, Inc. (Nasdaq: HGSI) today announced 12- week interim data from a Phase 2b clinical trial to evaluate the efficacy and safety of Albuferon (albumin- interferon alpha 2b) in combination with ribavirin in patients with genotype 1 chronic hepatitis C who are naive to interferon alpha- based treatment regimens.1 The results to date demonstrate that Albuferon in combination with ribavirin was safe, well tolerated and showed robust antiviral activity. A presentation of the full interim data will take place on April 29 at the European Association for the Study of the Liver (EASL).2
In a separate press release issued today, HGS reported the interim results of a Phase 2 clinical trial of Albuferon in combination with ribavirin in treatment- experienced patients with chronic hepatitis C.3- 4
David C. Stump, M.D., Executive Vice President, Drug Development, said, "The interim results available to date from our Phase 2b trial are encouraging and supportive of our broadening program of clinical study of Albuferon.1- 12 We believe that an interferon with less frequent dosing than pegylated interferon, and with comparable safety and efficacy, would be an important therapeutic option for patients with chronic hepatitis C. Based on the 12- week virologic response data from the Phase 2b study, Albuferon appears capable of meeting this target at doses of 900- 1200 mcg every 14 days. We are encouraged that the interim data at the 1200- mcg dose administered every two weeks show a trend for greater antiviral activity for Albuferon, compared with Pegasys administered every 7 days, with 75% of the patients in this group exhibiting a level of hepatitis C viral load below the level of quantitation, compared with 66% in the treatment group receiving 180 mcg of Pegasys at 7- day intervals. Response rates were somewhat lower at 12 weeks for the treatment group receiving 1200- mcg doses of Albuferon every 28 days, which suggests that higher doses will be required to optimize a 28- day dosing schedule. In other Phase 2 studies, we are evaluating Albuferon doses of 1500 mcg and 1800 mcg. Interim results show that these doses are well tolerated when given every 14 days and may have greater antiviral activity than the 900- mcg and 1200- mcg doses on the same schedule.3- 4
"The 12- week data from the Phase 2b trial show that Albuferon in combination with ribavirin was well tolerated at all doses studied, with no discontinuations due to hematological abnormalities. The fewest dose reductions due to drops in hematologic cell counts were observed in the treatment group receiving 1200 mcg at 28- day intervals. These data support the continuing exploration of a treatment regimen that administers Albuferon at 28- day intervals with higher exposures than those investigated in the current trial. We look forward to presentation of the complete Phase 2b 12- week interim data set at the EASL meeting in April, and to continuing the evaluation of Albuferon in combination with ribavirin at higher doses and over the full term of the current study. Assuming that positive data continue to emerge from this Phase 2b study and our other ongoing Phase 2 trials of Albuferon, we plan to meet with clinical experts and regulatory authorities to discuss the initiation of Phase 3 development of Albuferon by year- end 2006."
The Phase 2b trial is a randomized, open- label, multi- center, active- controlled, dose- ranging study being 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 been enrolled and 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 13). The fourth treatment group serves as the active control group and receives 180- mcg doses of subcutaneously administered peginterferon alfa- 2a (Pegasys) at 7- day intervals. 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, vs. Pegasys with ribavirin, in interferon alpha- naive patients with chronic hepatitis C genotype 1. The primary efficacy endpoint is sustained virologic response ( SVR), defined as undetectable virus 24 weeks after completion of 48 weeks of treatment.
Virologic response and laboratory data are available on 458 patients through Week 12 of the Phase 2b trial. The data show the following percentages of patients with hepatitis C (HCV) RNA viral load below the level of quantitation (43 IU/mL) at Week 12: 66% (75/114) in the treatment group receiving 180- mcg doses of Pegasys at 7- day intervals; 75% (82/110) in the treatment group receiving 1200 mcg of Albuferon at 14- day intervals (p=0.15 vs. Pegasys); 69% (82/118) in the treatment group receiving 900 mcg of Albuferon at 14- day intervals (p=0.55 vs. Pegasys); and 53% (62/116) in the treatment group receiving 1200 mcg of Albuferon at 28- day intervals (p=0.056 vs. Pegasys). Data also are available on early virologic response at Week 12 (EVR12). (Early virologic response is defined as a >2 log - 99% or greater - reduction in HCV RNA viral load.) The data show the following percentages of patients achieving EVR12: 89% (101/114) in the treatment group receiving 180- mcg doses of Pegasys at 7- day intervals; 90% (99/110) in the treatment group receiving 1200 mcg of Albuferon at 14- day intervals (p=0.73 vs. Pegasys); 84% (99/118) in the treatment group receiving 900 mcg of Albuferon at 14- day intervals (p=0.30 vs. Pegasys); and 76% (88/116) in the treatment group receiving 1200 mcg of Albuferon at 28- day intervals (p=0.011 vs. Pegasys).
Albuferon in combination with ribavirin was well tolerated. The incidence and duration of flu- like symptoms was similar in all groups, except for a higher rate of chills in the Albuferon groups. In general, the incidence and severity of other adverse events was similar across treatment groups, except for a higher rate of respiratory symptoms (primarily mild cough and dyspnea) in the Albuferon groups and a higher rate of psychiatric symptoms in the Pegasys group. Discontinuations due to adverse events were observed by treatment group as follows: 3 in the 180- mcg 7- day Pegasys cohort (n=114); 8 in the 1200- mcg 14- day Albuferon cohort (n=110); 3 in the 900- mcg 14- day Albuferon cohort (n=118); and 7 in the 1200- mcg 28- day Albuferon cohort (n=116). T here were no discontinuations due to reductions in hematologic cell counts, which appeared to be maximal by Week 8, and were well managed with dose reductions in all treatment groups. The incidence of dose reduction due to hematologic abnormalities was similar in the Pegasys group and in Albuferon groups administered every 14 days, but occurred less frequently in the group administered 1200 mcg Albuferon every 28 days. The rate of emergent antibodies to interferon was significantly lower in the Albuferon treatment groups (3%) compared with the Pegasys treatment group (18%) through the first 12 weeks of treatment (p<0.0001).
HGS also announced that it has completed enrollment, randomization and initial dosing of 46 patients in a new Phase 2 clinical trial of Albuferon in combination with ribavirin in treatment- naive patients with genotype 2 or genotype 3 chronic hepatitis C. The Phase 2 trial is a randomized, open label, multi- center study being conducted in Canada. Participants have been randomized into two treatment cohorts, with all patients receiving 1500- mcg doses of Albuferon in combination with ribavirin for 24 weeks. Albuferon is administered every 14 days in one cohort and administered every 28 days in the other cohort. All patients receive oral daily ribavirin at 800 mg in two divided doses. The primary efficacy endpoint of the Phase 2 study is sustained virologic response ( SVR), defined as undetectable hepatitis C virus (HCV) 24 weeks after completion of 24 weeks of treatment. Secondary endpoints include rapid virologic response (undetectable HCV RNA viral load) at Week 4, and safety and quality of life at Week 24.
Albuferon is a novel, long- acting form of interferon alpha 2b. 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.
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. 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 REPORTS POSITIVE INTERIM RESULTS OF PHASE 2 TRIAL OF ALBUFERON IN COMBINATION WITH RIBAVIRIN IN TREATMENT- EXPERIENCED PATIENTS WITH CHRONIC HEPATITIS C
- Results to date show Albuferon is safe, well tolerated and shows robust antiviral activity -
- Interim data support further evaluation of higher dose levels with a 28- day administration schedule -
ROCKVILLE, Maryland - March 14, 2006 - Human Genome Sciences, Inc. (Nasdaq: HGSI ) today reported the interim results of a Phase 2 clinical trial to evaluate the safety, tolerability and efficacy of Albuferon (albumin- interferon alpha 2b) in combination with ribavirin 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 ribavirin was safe, well tolerated and showed robust antiviral activity. A presentation of the full interim data will take place on April 30 at the European Association for the Study of the Liver (EASL). 1
In a separate press release issued today, HGS announced the interim results of a larger Phase 2b clinical trial of Albuferon in combination with ribavirin, versus Pegasys with ribavirin, in treatment- naive patients with chronic hepatitis C genotype 1.2
David C. Stump, M.D., Executive Vice President, Drug Development, said, "I continue to be encouraged by the growing evidence that Albuferon in combination with ribavirin is safe and well tolerated, with robust and durable antiviral activity. The results available from the first three treatment groups for the 48- week treatment period of the Phase 2 study demonstrate that Albuferon was well tolerated at all doses administered, with no significant increase in severity of adverse events between Week 12, Week 24 and Week 48. Decreases in hematologic cell counts were well managed with dose reductions, and returned to baseline following the completion of therapy. I am also encouraged by the emerging evidence of clinically significant antiviral effect. At Week 48, 30% of the patients in the three lower- dose treatment groups had no detectable hepatitis C RNA viral load. At the 12- week follow- up point, 18% of the patients continued to have no detectable hepatitis C RNA viral load. These data are quite positive, considering that they were observed in a heavily pretreated population, nearly two thirds of whom previously failed to respond to treatment regimens that included pegylated interferon alpha plus ribavirin.
"The results to date also indicate that both the 1500- mcg and the 1800- mcg doses were well tolerated, with safety data generally similar to the lower- dose treatment groups and with greater antiviral activity. Results at the higher doses in the current Phase 2 study encourage us to evaluate a regimen in interferon- naive patients that combines higher doses of Albuferon with ribavirin administered at intervals of 28 days. We look forward to the complete presentation of these interim data at the EASL meeting in April, and to continuing the evaluation of Albuferon in combination with ribavirin at higher doses and over the full term of the current study."
The Phase 2 trial is a randomized, open- label, multi- center, dose- escalation study, and 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, 3- 5Patients 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. The primary efficacy endpoint is sustained virologic response ( SVR ), defined as undetectable virus 24 weeks after the end of therapy.
Data are available through Week 48 (end of treatment) 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. Of the subjects in the first three Albuferon treatment groups, 65% (46/71) 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, 30% (21/71) of the patients 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, 18% (13/71) of these heavily pretreated patients had no detectable hepatitis C RNA viral load.
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, and generally similar to the adverse events observed in the 2 higher- dose groups (24- Week data for the 1800- mcg and 1500- mcg cohorts). There was no increase in severity of adverse events beyond Week 12. Hematologic reductions 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 hematologic dose reductions 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, or in administration of higher doses.
Data are available through Week 24 for treatment groups receiving, in combination with ribavirin, Albuferon doses of 1500 mcg and 1800 mcg, respectively, administered subcutaneously every 14 days. At Week 24, the same percentage of patients in the 1500- mcg and 1800- mcg Albuferon treatment groups exhibited no detectable hepatitis C RNA viral load: 32% (7/22) in each of the two groups. Data also are available for the 1500- mcg and 1800- mcg Albuferon treatment groups on early virologic response (EVR12). EVR12 is defined as a >2 log (99% or greater) reduction in HCV RNA viral load at Week 12. In the 1500- mcg treatment group, 41% or the patients (9/22) achieved EVR12. In the 1800- mcg treatment group, 59% (13/22) of the patients achieved EVR12.
The 1800- mcg Albuferon treatment group had a higher percentage of genotype 1 hepatitis C patients who had 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: 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; 15% (2/13) receiving 1200 mcg of Albuferon at 28- day intervals; 27% (4/15) receiving 1500 mcg of Albuferon at 14- day intervals; and 32% (6/19) 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: 42% (5/12) in the treatment group receiving 900 mcg of Albuferon at 14- day intervals; 25% (4/16) receiving 1200 mcg of Albuferon at 14- day intervals; 23% (3/13) in the treatment group receiving 1200 mcg of Albuferon at 28- day intervals; 33% (5/15) receiving 1500 mcg of Albuferon at 14- day intervals; and 63% (12/19) receiving 1800 mcg of Albuferon at 14- day intervals. 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.
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.
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.
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