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[DewDiligence]

HGSI Reports Treatment-Refractory Albuferon Data

[This PR is unusually challenging to parse because the trial in question has five arms and it is only near the end of the PR that it says what the trial design actually was: one arm each at 900, 1200, 1500, and 1800mcg every two weeks and one arm at 1200mcg monthly, all arms to receive 48 weeks of treatment and 24 weeks of follow-up. (Note that it was one of the *middle* doses that was given monthly.) Despite the parsing difficulty, it’s possible to extract a few key points: 1) The data for the monthly dosing arm, which is arguably the most important one from a commercial standpoint, looks tepid. 2) Albuferon generated antibodies against the drug itself in some patients; although HGSI says these antibodies did not interfere with efficacy. All told, these data seem to be no big deal. (HGSI’s stock price dropped 20% in mid-March when earlier data from this trial and the one in treatment-naïve HCV patients were released.) I think it’s fair to say that Albuferon, a conjugation of interferon and albumin to extend the half-life, has not lived up to the early hype surrounding HGSI’s albumin-technology platform.]

http://biz.yahoo.com/prnews/060501/nym115.html?.v=33

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Human Genome Sciences Presents Interim Results of Phase 2 Trial of Albuferon(TM) with Ribavirin in Patients with Chronic Hepatitis C Who Failed to Respond to Previous Therapy

Monday May 1, 7:02 am ET

- Data support further evaluation of higher-dose Albuferon with monthly administration -

- Interim results to date demonstrate Albuferon is safe, well tolerated and shows robust and durable antiviral activity -

ROCKVILLE, Md., May 1 /PRNewswire-FirstCall/ -- 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(TM) (albumin-interferon alpha 2b) in combination with ribavirin in patients with chronic hepatitis C (HCV) who failed to respond to previous interferon alpha-based treatment regimens. The results to date -- presented over the weekend at the 41st Annual Meeting of the European Association for the Study of the Liver (EASL)(1) -- demonstrate that Albuferon in combination with ribavirin was safe, well tolerated and showed robust and durable antiviral activity. (In a separate press release today, HGS announced the interim results of a larger Phase 2b clinical trial of Albuferon with ribavirin in treatment-naive patients with chronic hepatitis C genotype 1.)

Vinod K. Rustgi, M.D., Co-Director of the Transplant Institute at Georgetown University School of Medicine (Washington, DC), and a clinical investigator in the Phase 2 trial, said, "The interim results of the Phase 2 study in treatment non-responders showed that Albuferon was well tolerated, with robust and durable antiviral activity. At Week 48, 31% of the patients in the three lower-dose treatment groups had no detectable hepatitis C RNA viral load. The preliminary rate of sustained virologic response (SVR) in these heavily pretreated patients is surprisingly high at 20%, based on the Week 12 follow-up point after the end of 48 weeks of treatment. The relapse rate is low. Few viral breakthroughs were observed. The treatment group receiving 1200-mcg Albuferon every four weeks was able to maintain HCV RNA negativity. This isn’t much detail on the monthly arm, although data on the genotype-1 subset of this arm are given later in the PR.] Based on data available through Week 24, the 1800-mcg Albuferon dose cohort showed the highest rates of HCV RNA negativity In genotype 1 patients who previously failed to respond to treatment with pegylated interferon and ribavirin. We look forward to continuing the evaluation of Albuferon in combination with ribavirin over the full term of the current study."

David C. Stump, M.D., Executive Vice President, Drug Development, Human Genome Sciences, said, "I am encouraged by the emerging evidence of Albuferon's clinically significant antiviral effect. One of the most important areas of medical need in the treatment of chronic hepatitis C is those patients infected with genotype 1 hepatitis C who have failed previous treatment with the standard-of-care combination of pegylated interferon and ribavirin. In this most difficult to treat subgroup, 63% of the patients receiving 1800-mcg doses of Albuferon once every two weeks achieved early virologic response at Week 12 (EVR12). At Week 24, no detectable HCV RNA viral load was observed in 32% of the genotype 1 non-responders to standard- of-care in the 1800-mcg treatment group. Across the total patient population, the safety data from both of the higher-dose treatment groups was generally similar to safety data from the lower-dose treatment groups, but with greater antiviral activity. These results encourage us to evaluate a regimen in interferon-naive patients that combines higher doses of Albuferon with ribavirin administered at intervals of 28 days."

The Phase 2 interim results were reported in Vienna yesterday, April 30, 2006, at the 41st Annual Meeting of the European Association for the Study of the Liver (EASL) in an oral presentation entitled "A Phase 2 Dose-Escalation Study of Albumin Interferon Alfa-2b Combined with Ribavirin in Non-Responders to Interferon-Based Therapy for Chronic Hepatitis C Infection." Data are available through Week 60 (48 weeks of treatment plus 12 weeks of follow-up) on 71 patients who were enrolled in parallel and randomized into three Albuferon treatment groups: 900 mcg administered subcutaneously every 14 days, 1200 mcg administered subcutaneously every 14 days, and 1200 mcg administered subcutaneously every 28 days -- with all patients receiving weight-based oral ribavirin daily at 1000 or 1200 mg in two divided doses. Of the subjects in the first three Albuferon treatment groups, 63% (45/71) were non-responders to pegylated interferon alpha, and 93% (66/71) were infected with genotype 1 hepatitis C. More than 60% of the study subjects had received more than one prior interferon alpha-based treatment regimen, and the mean duration of prior therapy was approximately 15 months. At Week 48, 31% (22/71) of the patients in the 900-mcg and 1200-mcg Albuferon treatment groups exhibited no detectable HCV RNA viral load. Antiviral activity was similar for the 14-day and 28-day Albuferon treatment groups. At the Week 12 follow-up after the end of treatment, 20% (14/71) of these heavily pretreated patients had no detectable hepatitis C RNA viral load. The primary efficacy endpoint in the trial is sustained virologic response (SVR), defined as undetectable virus 24 weeks after the end of therapy.

The 1800-mcg Albuferon treatment group had a higher percentage of genotype 1 hepatitis C patients who failed to respond to previous treatment with a combination of pegylated interferon and ribavirin -- 91% (20/22) versus an average of 66% (61/93) in the other Albuferon treatment groups combined. At Week 24 in this important and most difficult to treat subgroup, the data show the following percentages of patients with no detectable HCV RNA viral load: 15% (2/13) in the treatment group receiving 1200 mcg of Albuferon at 28-day intervals; 17% (2/12) in the treatment group receiving 900 mcg of Albuferon at 14-day intervals; 19% (3/16) in the treatment group receiving 1200 mcg of Albuferon at 14-day intervals; 27% (4/15) in the treatment group receiving 1500 mcg of Albuferon at 14-day intervals; and 32% (6/19) in the treatment group receiving 1800 mcg of Albuferon at 14-day intervals. Data also are available for this subgroup on early virologic response (EVR12). The data show the following percentages of patients achieving EVR12: 23% (3/13) in the treatment group receiving 1200 mcg of Albuferon at 28-day intervals; 42% (5/12) in the treatment group receiving 900 mcg of Albuferon at 14-day intervals; 25% (4/16) in the treatment group receiving 1200 mcg of Albuferon at 14-day intervals; 33% (5/15) in the treatment group receiving 1500 mcg of Albuferon at 14-day intervals; and 63% (12/19) in the treatment group receiving 1800 mcg of Albuferon at 14-day intervals.

Albuferon in combination with ribavirin was well tolerated. The incidence of adverse events was similar across the three dose groups for which 48-week data are available. No increase in severity of adverse events was observed beyond Week 12. Decreases in hematologic cell counts were maximal by Week 8, were well managed with dose reductions, and returned to baseline following the completion of therapy (Week 12 follow-up after the end of 48 weeks of treatment). Albuferon appeared to be better tolerated in the treatment group receiving 1200 mcg administered subcutaneously every 28 days, with fewer dose reductions due to hematology observed in this group. No subject required discontinuation of either Albuferon or ribavirin for hematological abnormalities. Overall, the rate of treatment-emergent Albuferon antibodies is 10%, with pre-existing antibodies detected in 17% of study participants. There was no apparent correlation between the emergence of antibodies and antiviral response, adverse events or pharmacokinetics. No overall increase in the emergence of antibodies was observed between Week 12, Week 24 and Week 48. Safety data available for the 1500-mcg and 1800-mcg treatment groups through Week 24 are generally similar to the lower-dose Albuferon treatment groups. No increase in the emergence of Albuferon antibodies was observed related to administration of the higher doses.

The Phase 2 trial is a randomized, open-label, multi-center, dose-escalation study of Albuferon in combination with ribavirin in patients who have failed to respond to interferon-based therapy for chronic hepatitis C. The trial is being conducted in the United States. The study design states that approximately 50 percent of the subjects enrolled should be patients who have failed combination therapy that included pegylated interferon alpha plus ribavirin. A total of 115 patients have been enrolled into 5 Albuferon treatment groups that are receiving doses of Albuferon ranging from 900-1800 mcg. Patients were initially randomized into 3 Albuferon treatment groups (900 mcg at 14-day intervals, 1200 mcg at 14-day intervals, and 1200 mcg at 28-day intervals). Following evaluation of safety data, 2 additional cohorts were enrolled sequentially (1500 mcg at 14-day intervals and 1800 mcg at 14-day intervals). Patients are receiving Albuferon administered subcutaneously, with all patients receiving weight-based oral ribavirin daily at 1000 or 1200 mg in two divided doses. Patients in the trial will receive 48 weeks of treatment, with an additional 24 weeks of follow-up. The primary objective of the Phase 2 study is to evaluate the safety and tolerability of Albuferon in combination with ribavirin. The study also is evaluating the efficacy of Albuferon in combination with ribavirin.

Albuferon is a novel, long-acting form of interferon alpha. It is a Human Genome Sciences drug made possible by the company's proprietary albumin fusion technology, which was used to improve the pharmacological properties of interferon alpha. Recombinant interferon alpha is approved for the treatment of hepatitis C, hepatitis B and a broad range of cancers. Human Genome Sciences is developing Albuferon for use in the treatment of chronic hepatitis C.

Hepatitis C infection is an inflammation of the liver caused by the hepatitis C virus. It is the most common chronic blood-borne infection in the developed world. It is estimated that as many as 170 million people worldwide are infected with hepatitis C virus. This includes nearly four million people in the United States. The hepatitis C virus is transmitted primarily through significant or repeated exposures to infected blood. Intravenous drug use and sexual contact with infected persons account for the majority of new hepatitis C infections. When detectable levels of the hepatitis C virus in the blood persist for at least six months, a person is diagnosed as having chronic hepatitis C.

Human Genome Sciences is a company with the mission to discover, develop, manufacture and market innovative drugs that serve patients with unmet medical needs, with a primary focus on protein and antibody drugs.
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