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Plan to Advance Albuferon to Phase 3 in Chronic Hepatitis C
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HUMAN GENOME SCIENCES REPORTS ON PROGRESS TOWARD COMMERCIALIZATION AND ANNOUNCES 2006 GOALS AT JPMORGAN HEALTHCARE CONFERENCE
- 2006 Focus on Accelerating Progress Toward Commercialization -
- Plan to Advance LymphoStat-B to Phase 3 in SLE -
- Plan to Advance Albuferon to Phase 3 in Chronic Hepatitis C -
- Working to Achieve Order to Supply ABthrax for the Strategic National Stockpile -
- Phase 2 Trials to Begin for HGS-ETR1 with Chemotherapy in Hematopoietic Cancers -
- Validation of Large-Scale Manufacturing Facility Expected -
- CoGenesys Spin-Off Transaction Expected to Be Completed -
ROCKVILLE, Maryland - January 10, 2006 - Human Genome Sciences, Inc. (Nasdaq: HGSI) will report on its progress toward commercialization and announce 2006 goals during a presentation tomorrow by President and Chief Executive Officer H. Thomas Watkins to financial analysts and investors at the 24 th Annual JPMorgan Healthcare Conference in San Francisco.1
Mr. Watkins said, "Human Genome Sciences has made steady progress toward commercialization throughout 2005, and we expect to accelerate that progress in 2006. We have made significant progress in clarifying the development pathway for our most promising compounds. Phase 2 clinical results for LymphoStat-B demonstrated significant reduction of disease activity in patients who are seropositive for systemic lupus erythematosus (SLE). Together with our collaborator, GlaxoSmithKline, we are actively planning for Phase 3, and we expect to initiate Phase 3 development of LymphoStat-B in SLE in 2006. A Phase 2b trial of Albuferon in combination with ribavirin compared to Pegasys is currently underway. We plan to evaluate 12-week interim data in Spring 2006. We plan to initiate Phase 3 development of Albuferon by year-end 2006, assuming positive interim results of the Phase 2b study in the first half of the year. We are working to achieve an order from the U.S. Government to supply ABthrax for the Strategic National Stockpile. If we are successful, the ABthrax order will produce Human Genome Sciences' first product sales. HGS-ETR1 is also moving forward. Our Phase 2 trial of HGS-ETR1 as monotherapy produced clinical responses in patients with non-Hodgkin's lymphoma. The Phase 2 results support further evaluation in combination with other therapeutic agents. In 2006, we plan to initiate Phase 2 development of HGS-ETR1 in combination with chemotherapy in hematopoietic cancers."
In a separate press release issued earlier today, Human Genome Sciences announced that it has received a $5 million milestone payment from its collaborator, GlaxoSmithKline (GSK), related to GSK's filing of an Investigational New Drug (IND) application to begin Phase 1 clinical trials of GSK716155 (formerly known as Albugon) for potential use in the treatment of diabetes.2 An additional press release issued jointly earlier today by CoGenesys, a division of HGS, and PDL BioPharma, Inc. (Nasdaq: PDLI) announced that the companies have entered into a worldwide licensing agreement that provides PDL certain exclusive rights to intellectual property for an undisclosed target antigen discovered by HGS.3
"We are also making progress in advancing our partnering objectives," Mr Watkins said. "Both LymphoStat-B and HGS-ETR1 are now partnered with GSK, and we are working closely with our GSK colleagues in planning for Phase 3 development of LymphoStat-B. GSK has advanced relacatib, the small-molecule cathepsin K inhibitor that GSK discovered using HGS technology, to Phase 2 trials in the treatment of bone metastases. HGS is entitled to an additional milestone payment if relacatib moves into registration and will receive royalties if the compound is commercialized. GSK has filed an IND seeking to initiate Phase 1 trials of GSK716155 (formerly Albugon), and HGS received $12 million in payments during 2005 related to the achievement of this and other GSK716155 preclinical, manufacturing and clinical development milestones. In 2006, we will consider a number of collaboration opportunities for Albuferon. We expect to complete the CoGenesys transaction in 2006, and will continue to explore additional ways to monetize less critical assets that we are unlikely to develop internally. We also completed construction of our large-scale manufacturing facility in 2005, and we expect to complete the validation of this important strategic asset in mid-2006. We will concentrate our efforts in 2006 on accelerating our progress toward commercialization, while at the same time remaining committed to ensuring the highest standards of quality throughout our company."
During his January 11 presentation, Mr. Watkins will discuss the following updates on progress and 2006 goals for the company's clinical development pipeline and other areas of priority focus:
PIPELINE PROGRESS AND GOALS FOR 2006
LymphoStat-B (belimumab), a human monoclonal antibody that neutralizes BLyS (B-lymphocyte stimulator)
The lead indication for LymphoStat-B is systemic lupus erythematosus (SLE). HGS is also developing LymphoStat-B for use in treating rheumatoid arthritis (RA) and may develop it for other indications. The FDA has selected LymphoStat-B for the treatment of SLE for inclusion in its Continuous Marketing Application Pilot 2 Program and has designated it a Fast Track Product. 4
In July 2005, GlaxoSmithKline exercised its option under a June 1996 agreement to develop and commercialize LymphoStat-B jointly with Human Genome Sciences. Under the terms of the agreement, GSK and Human Genome Sciences will share equally in Phase 3/4 development costs, and will share equally in sales and marketing expenses and profits of any product that is commercialized under the agreement, under a co-development and co-promotion agreement, the remaining terms of which are being negotiated by the parties. 5
The results of a Phase 2 trial of LymphoStat-B in SLE were announced in October 2005. The results demonstrated that LymphoStat-B significantly reduced SLE disease activity at Week 52 in seropositive6 patients, as measured by both SELENA SLEDAI 7 (p=0.021) and the Physician's Global Disease Assessment (p=0.016).8 Seropositive patients represented 75% (337/449) of the total study population. The Phase 2 results also added significantly to existing preclinical and clinical evidence of LymphoStat-B's biological activity in SLE.9-16 Data from the Phase 2 trial demonstrated that LymphoStat-B produced targeted and statistically significant reductions versus placebo in all active-treatment arms in both circulating B cells (CD 20+ and other subsets) and anti-dsDNA autoantibodies. The results in active treatment groups showed a 29% median reduction in anti-dsDNA autoantibodies among patients positive for anti-dsDNA at baseline (p=0.0018), and a 33% median increase in C4 complement at Week 52 among patients with low C4 at baseline (p=0.014). Signs of drug activity were observed across the range of doses studied, including the lowest dose of 1 mg/kg. Results further showed that LymphoStat-B was well tolerated with no clinically significant differences from placebo in adverse events, serious adverse events, laboratory abnormalities or infection rates. HGS expects that a full presentation of data from the Phase 2 trial of LymphoStat-B in SLE will take place at an appropriate scientific conference in the first half of 2006.
In November 2005, HGS presented the results of a Phase 2 clinical trial of LymphoStat-B in patients with rheumatoid arthritis.17-20 The results demonstrated that LymphoStat-B met the study's primary safety and efficacy endpoints, and significantly reduced RA disease activity, as measured by ACR 2021 response at Week 24. The rate of improvement in ACR 20 response at Week 24 was 35% in the 1-mg/kg active-treatment group, and 29% in all active-treatment groups combined - approximately double the 16% rate of improvement observed for the placebo group (p=0.0097 and p=0.021, respectively). All participants in the study received standard-of-care therapy. Results showed that LymphoStat-B was safe and well tolerated with no clinically significant differences from placebo in adverse events, serious adverse events or laboratory abnormalities. Biological activity data from the study suggest a potential role for LymphoStat-B in the treatment of RA, SLE and other autoimmune diseases. Additional Phase 2 study of LymphoStat-B is warranted in RA.
In 2006, HGS plans to initiate Phase 3 development of LymphoStat-B in systemic lupus erythematosus. The company also plans to determine the best route forward for other potential indications for LymphoStat-B, including rheumatoid arthritis and B-cell cancers.
Albuferon (albumin-interferon alpha 2b), a novel long-acting form of interferon alpha for the treatment of chronic hepatitis C (HCV)
In April 2005, the results of a Phase 2 trial of Albuferon as monotherapy demonstrated that Albuferon was well tolerated and showed robust antiviral activity and durable dose-dependent reductions in hepatitis C viral load in 56 patients with HCV who were naive to interferon-alpha treatments. 22-23 The primary efficacy endpoint of the Phase 2 study 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. 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. 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 - a level which has previously been shown to be predictive of sustained virologic response (SVR) in treatment with the pegylated interferons.24 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. 25-26 These data are strongly supportive of further evaluation in a larger study over a longer period of time in treatment-naive patients.
In November 2005, HGS reported the interim results of a Phase 2 trial 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. 27-28 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. The results to date demonstrate that Albuferon in combination with RBV was safe, well tolerated and showed antiviral activity in all treatment groups for which data are available (71 patients who had been randomized into 3 Albuferon treatment groups ranging from 900-1200 mcg). At Week 24, 30% of the patients had no detectable hepatitis C RNA viral load. (The primary efficacy endpoint of the study 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. HGS expects additional interim results, including data from higher dose cohorts, to be presented at an appropriate scientific meeting in the first half of 2006.
Phase 2 results to date are strongly supportive of a Phase 2b comparative trial of Albuferon in combination with ribavirin, vs. Pegasys, in interferon-naive patients. HGS completed enrollment, randomization and initial dosing of 458 patients in the Phase 2b study in October 2005. 29 The Phase 2b trial is a randomized, open-label, multi-center, active-controlled, dose-ranging study conducted outside the U.S. 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. The primary objectives of the Phase 2b study are to evaluate the efficacy and safety of Albuferon in combination with ribavirin in interferon alpha-naive patients with chronic hepatitis C genotype 1. The primary efficacy endpoint is sustained virologic response, defined as undetectable virus at 24 weeks after completion of 48 weeks of treatment.
HGS expects to have 12-week data from the Phase 2b comparative combination trial of Albuferon available in Spring 2006. HGS plans to initiate Phase 3 development of Albuferon in patients with chronic hepatitis C before year-end 2006, assuming that data emerging from the Phase 2b study in the first half of the year are positive. HGS is also considering collaboration opportunities for Albuferon.
ABthrax (raxibacumab), a human monoclonal antibody to Bacillus anthracis protective antigen, for use in treating anthrax disease
In October 2005, HGS announced that it has been awarded a two-phase contract to supply ABthrax to the U.S. Government. 30 Under the first phase of the contract, HGS has supplied ABthrax to the U.S. Department of Health and Human Services (HHS) for comparative laboratory testing. Under the second phase of the contract, the U. S. Government has the option to place an order within one year to supply ABthrax for the Strategic National Stockpile for use in the treatment of anthrax disease. The HHS comparative testing results, along with Human Genome Sciences' own preclinical and clinical study results, will form the basis of the U.S. Government's decision process for exercising its option for additional product for the Strategic National Stockpile.
In 2006, HGS will work toward achieving an order from the U.S. Government under the second phase of the contract to supply ABthrax for the Strategic National Stockpile. The company will also pursue additional opportunities to supply ABthrax.
CCR5 mAb, a human monoclonal antibody that specifically recognizes and binds the CCR5 receptor and prevents the entry of the HIV-1 virus into the cell, for use in the treatment of HIV/AIDS
In March 2005, HGS announced the initiation of dosing of patients in a Phase 1 trial of CCR5 mAb in patients infected with the HIV-1 virus who are not receiving concurrent antiretroviral therapy. 31
HGS expects to complete the Phase 1 trial in the first half of 2006, and will then determine the development pathway for CCR5 mAb based on Phase 1 results.
HGS-ETR1 (mapatumumab), a human monoclonal antibody to TRAIL receptor 1 for use in treating hematopoietic and solid tumors
In August 2005, GSK exercised its option under a June 1996 agreement to develop and commercialize HGS-ETR1 jointly with Human Genome Sciences. 32 Under the terms of the agreement, GSK and Human Genome Sciences will share equally in Phase 3/4 development costs, and will share equally in sales and marketing expenses and profits of any product that is commercialized under the agreement, under a co-development and co-promotion agreement, the remaining terms of which are being negotiated by the parties.
During 2005, HGS completed and reported the results of Phase 2 trials of HGS-ETR1 as monotherapy in advanced non-small cell lung cancer, advanced colorectal cancer, and advanced non-Hodgkin's lymphoma. 33-38 The results of these Phase 2 trials support additional Phase 2 study of HGS-ETR1 in combination with chemotherapeutic agents.
Data reported in December 2005 from the Phase 2 trial of HGS-ETR1 in patients with non-Hodgkin's lymphoma demonstrated that HGS-ETR1 was capable of producing clinical responses when administered as monotherapy in these patients. 33-34 The 40 patients participating in the study had received up to 12 previous cancer treatment regimens, with 69% (28/40) having received 3 or more prior regimens. Clinical responses (1 complete response and 2 partial responses) were observed in three of these heavily pretreated patients (8%, n=40), all of whom had been diagnosed with follicular lymphomas. Stable disease was observed in an additional 30% (12/40) of the patients. To date, 7 patients (18%, n=40) remain without progression of disease, with stable disease or response enduring 9-18 months. Follicular lymphomas are of particular interest since the 3 clinical responses were observed in patients with follicular lymphomas. Clinical responses were observed in 3/17 (18%) patients with follicular lymphomas, and 11/17 (65%) exhibited either response or stable disease. The results showed that HGS-ETR1 is well tolerated, with minimal toxicity, and can safely be administered intravenously every 21 days at doses up to 10 mg/kg. The results of the Phase 2 trial in non-Hodgkin's lymphoma support further evaluation of HGS-ETR1 in combination with chemotherapeutic agents in hematologic malignancies.
HGS reported the interim results of two Phase 1b trials of HGS-ETR1 in combination with chemotherapy in November 2005. 39-41 The data presented showed that HGS-ETR1 in combination with chemotherapy was well tolerated and could be administered safely and repetitively at the doses and schedules evaluated in patients with advanced solid tumors. Partial response was observed in a number of patients in each of the studies. These results support further evaluation of HGS-ETR1 in combination with chemotherapy in Phase 2 trials.
HGS plans to initiate Phase 2 development of HGS-ETR1 in combination with chemotherapy in hematopoietic cancers in 2006.
HGS-ETR2 and HGS-TR2J, human monoclonal antibodies to TRAIL receptor 2, for use as treatments for advanced cancers
HGS completed two Phase 1 trials of HGS-ETR2 in advanced solid tumors and reported the results in November 2005. 42-44 The results of the two studies demonstrated that HGS-ETR2 is well tolerated at doses as high as 10-mg/kg in patients with advanced solid tumors. The DLT (dose-limiting toxicity) dose has been identified as 20 mg/kg. In each study for which data were presented, stable disease was observed in a number of patients. The results warrant additional study of HGS-ETR2 in Phase 2 trials to evaluate its potential for use in the treatment of specific cancers.
A Phase 1 trial of HGS-TR2J, a human monoclonal antibody to TRAIL receptor 2, continues to enroll patients in Canada.
HGS plans to reach go/no go decisions in 2006 regarding Phase 2 development of HGS-ETR2 as a single-agent and/or in combination with chemotherapy.
PROGRESS OF OTHER PRODUCT OPPORTUNITIES
GSK716155 (formerly known as Albugon), a novel long-acting form of glucagon-like peptide-1, GLP-1 for use in the treatment of diabetes - to which GSK has acquired exclusive worldwide rights
In August 2005, HGS announced that it has received $7 million in payments from its collaborator, GSK, related to the achievement of manufacturing and preclinical development milestones for GSK716155.45 In a separate press release issued earlier today 2, HGS announced that it has received a $5 million milestone payment from GSK, related to GSK's filing of an Investigational New Drug (IND) application to begin Phase 1 clinical trials of GSK716155 for potential use in the treatment of diabetes. This milestone payment, which HGS will recognize as revenue in the fourth quarter of 2005, brings the total amount of payments received from GSK related to the progress of GSK716155 to $12 million in 2005.
These milestone payments were made pursuant to an agreement announced in October 2004, under which GSK acquired exclusive worldwide rights to develop and commercialize Albugon for all human therapeutic and prophylactic applications.46 Under the agreement, HGS is entitled to clinical development and commercial milestone payments that could amount to as much as $183 million, and additional milestones for other indications developed. HGS also will receive royalties on the annual net sales of any products developed and commercialized under the agreement.
Relacatib (GSK462795), a small-molecule drug discovered by GSK using HGS technology, which inhibits the activity of cathepsin K, an enzyme that appears to be implicated in osteoporosis, bone metastases, and certain other disorders causing bone degradation
GSK has advanced relacatib to Phase 2 clinical trials for the treatment of bone metastases. Relacatib is also in development for the treatment of osteoporosis and osteoarthritis.
Under the terms of an agreement signed in 1993, as amended in 1996, HGS is entitled to receive clinical development milestone payments and royalties for compounds discovered by GSK through the use of Human Genome Sciences' technology and intellectual property. Under the agreement, HGS will receive a milestone payment if relacatib moves into registration, and will receive royalties if the compound is commercialized. In addition, HGS has an option to co-promote in the North American and European markets.
Darapladib (GSK480848), a small-molecule drug discovered by GSK using HGS technology, inhibits the activity of lipoprotein-associated phospholipase A2 (Lp-PLA2), an enzyme associated with the development of atherosclerotic plaques
GlaxoSmithKline (GSK) has completed a Phase 2 clinical trial of 480848 47 and has indicated that it plans to advance 480848 to Phase 3 clinical development for the treatment of atherosclerosis.
Under terms of the 1993 agreement, HGS will receive a milestone payment if 480848 moves into registration, and will receive royalties if the compound is commercialized. In addition, HGS has an option to co-promote in the North American and European markets.
PROGRESS - MONETIZATION OF LESS CRITICAL ASSETS
Plan to Spin Off CoGenesys Division as Independent Company :
CoGenesys has made important progress since it was created as a division of Human Genome Sciences in the first quarter of 2005, and has demonstrated its ability to generate value through the early development of promising HGS assets. In December 2005, HGS announced that it has decided to spin off its CoGenesys division as an independent company that will focus on the early development of selected gene-based product opportunities and the monetization of certain HGS intellectual property and technology assets that are unlikely to be developed by HGS due to the company's priority focus on commercialization of the compounds in its clinical development pipeline. 48 CoGenesys will remain a division of HGS pending successful completion of funding from sources outside HGS.
In 2006, HGS plans to complete the CoGenesys transaction.
PDL BioPharma License Agreement Announced
In a separate press release issued jointly earlier today by CoGenesys, a division of HGS, and PDL BioPharma, it was announced that the companies have entered into a worldwide licensing agreement that provides PDL certain exclusive rights to intellectual property for an undisclosed target antigen discovered by HGS.3 Under terms of the agreement, CoGenesys is entitled to an upfront licensing fee, development milestone payments and royalties on future sales of antibody therapeutics developed by PDL against the target. PDL also will provide CoGenesys with access to its antibody humanization technology platform, which will help enable CoGenesys' own internal discovery and development programs.
Amgen License Agreement Announced
In a press release issued January 9, 2006, HGS announced a license agreement with Amgen under which Amgen has acquired exclusive worldwide rights to develop and commercialize therapeutic biological products for human use based on a human gene discovered by HGS that may have potential applications in autoimmune diseases, immune deficiencies or suppression, and cancer. 49 Amgen also has acquired non-exclusive worldwide rights for the development and commercialization of diagnostic products for human use based on the same gene. According to the terms of the agreement, HGS will receive an upfront payment and certain annual fees, as well as development milestone payments and royalties on annual net sales for therapeutic and diagnostic products successfully developed and commercialized using such rights.
HGS views the agreement with Amgen as one more step in its monetization of HGS intellectual property and technology assets that are unlikely to be developed by HGS internally. The company will continue to explore ways to monetize less critical assets in 2006.
PROGRESS - MANUFACTURING
HGS completed construction of its Large-Scale Manufacturing facility in 2005, and expects to complete equipment and facility validation in mid-2006. The Large-Scale Manufacturing facility is designed to meet the company's increasing need for protein and antibody production capacity as its product candidates continue their progress toward commercialization. HGS also has a strong and experienced manufacturing organization. This world-class manufacturing capability is a critically important asset that gives HGS a significant competitive advantage.
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