GlaxoSmithKline and Human Genome Sciences announce initiation of Phase 3 clinical trial of Lymphostat-B(R) in systemic lupus erythematosus
- Category: Antibodies
- Published on Wednesday, 14 February 2007 02:00
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LONDON, UK and ROCKVILLE, MD, USA | Feb 13, 2007 | GlaxoSmithKline PLC (GSK) and Human Genome Sciences, Inc. (Nasdaq: HGSI) today announced the initiation of dosing in BLISS-76, one of two pivotal Phase 3 clinical trials of LymphoStat-B® (belimumab) in patients with active systemic lupus erythematosus (SLE). LymphoStat-B is being developed by HGS and GSK under a definitive development and commercialisation agreement entered into in August 2006.
“We believe that LymphoStat-B could address the significant medical need of patients suffering from SLE, and advancing this novel therapeutic antibody to Phase 3 clinical trials is a major step toward that goal,” said H. Thomas Watkins, President and Chief Executive Officer, HGS. “Today’s announcement marks an important event in the development of our company into a commercial organisation.”
“Lupus is a life-threatening illness, which can have a devastating effect on patients living with the disease and their families,” said Dr. Yvonne Greenstreet, Senior Vice President, Research & Development, GSK. “We look forward to progressing the development of LymphoStat-B through the Phase 3 programme to enable us to bring this potentially important advance in the treatment of SLE to those who need it.”
About the Design of the LymphoStat-B Phase 3 Development Programme
HGS designed the Phase 3 development programme for LymphoStat-B in collaboration with GSK and leading international SLE experts. The programme includes two double-blind, placebo-controlled, multi-centre Phase 3 superiority trials to evaluate the efficacy and safety of LymphoStat-B plus standard of care, versus placebo plus standard of care, in the treatment of patients with active SLE. HGS has initiated dosing in the first Phase 3 trial, BLISS-76, in which the duration of therapy will be 76 weeks. The data from BLISS-76 will be analysed after 52 weeks in support of a potential Biologics License Application (BLA). The second Phase 3 trial, BLISS-52, is expected to begin in the first half of 2007, and will have a 52-week duration.
The primary efficacy endpoint of both studies is the patient response rate at Week 52, as defined by: A reduction from baseline in the SELENA SLEDAI score of at least 4 points; no worsening in Physician’s Global Assessment (with worsening defined as an increase in PGA of more than 0.30 points from baseline); no new BILAG A organ domain score and no more than 1 new BILAG B organ domain score from baseline. Important secondary endpoints will include the patient response rate at Week 76, the SF-36 Health Survey physical component summary score, fatigue measures, and the percentage of patients with reduction from baseline in average prednisone dose at Weeks 40-52. Safety and tolerability will be evaluated by an Independent Data Monitoring Committee throughout both studies.
In each of the two Phase 3 trials, approximately 810 patients will be enrolled and randomised to 1 of 3 treatment groups (1 mg/kg LymphoStat-B, 10 mg/kg LymphoStat-B, or placebo). Patients will be dosed intravenously on Days 0, 14 and 28, then every 28 days for the duration of the study. To be eligible for enrollment in the Phase 3 trials, patients must be serologically active, with unequivocally positive antinuclear antibody (ANA) test results assessed at 2 independent time points (HEp-2 ANA > 1:80 and/or anti-dsDNA > 30 IU/mL). Background SLE medications must be stable for a period of at least 30 days prior to Day 0.
About Phase 2 Trial Results
The results of a Phase 2 trial of LymphoStat-B in 449 patients with active SLE show that LymphoStat-B produced statistically significant reductions in disease activity versus placebo, exhibited clinically relevant biological activity, and appeared generally safe and well tolerated with frequency and severity of adverse events similar to placebo and no increase at higher doses. Among the Phase 2 study findings was a significantly improved response rate among serologically active patients at Week 52, as defined by an improvement in SELENA SLEDAI score of 4 points or greater, no BILAG worsening, and no worsening in Physician’s Global Assessment (46% for LymphoStat-B versus 29% for placebo, p<0.01). This combination of measures is the primary efficacy endpoint in the Phase 3 trials. Among LymphoStat-B patients who chose to participate in an optional 24-week extension phase of the Phase 2 study, the percentage of serologically active SLE patients who achieved the combined response rate increased from 46% at Week 52 to 56% at Week 76, with no increase in infections or infectious events observed over time.
About the Collaboration with GSK
In August 2006, HGS and GSK entered into a definitive co-development and co-commercialisation agreement under which HGS has responsibility for conducting the LymphoStat-B Phase 3 trials, with assistance from GSK. The companies will share equally in Phase 3/4 development costs, sales and marketing expenses, and profits of any product commercialised under the agreement.
LymphoStat-B is a human monoclonal antibody that specifically recognises and inhibits the biological activity of B-lymphocyte stimulator, or BLyS®. BLyS is a naturally occurring protein discovered by HGS that is required for the development of B-lymphocyte cells into mature plasma B cells. Plasma B cells produce antibodies, the body’s first line of defense against infection. In lupus, rheumatoid arthritis, and certain other autoimmune diseases, elevated levels of BLyS are believed to contribute to the production of autoantibodies – antibodies that attack and destroy the body’s own healthy tissues. The presence of autoantibodies appears to correlate with disease severity. Preclinical and clinical studies demonstrate that B-cell antagonists can reduce autoantibody levels and help control autoimmune disease activity.
LymphoStat-B was generated by HGS through a collaboration with Cambridge Antibody Technology. It has received a Fast Track Product designation from the FDA for its potential use in treating SLE and has been selected for participation in the FDA’s Continuous Marketing Application Pilot 2 Programme. The FDA has provided a Special Protocol Assessment agreeing to the LymphoStat-B Phase 3 clinical development programme in patients with active SLE. Agreement has also been received from the European Agency for the Evaluation of Medicinal Products (EMEA) on the major components of the LymphoStat-B Phase 3 clinical development programme, including the primary efficacy endpoint measures, target patient population, and dose selection.
About Systemic Lupus Erythematosus
Systemic lupus erythematosus (SLE) is a chronic, life-threatening disease. The Lupus Foundation of America estimates that approximately 1.5 million Americans suffer from various forms of lupus, including SLE. More than 300,000 people are afflicted with SLE in the United Statesalone. Lupus can occur at any age, but appears mostly in young people between the ages of fifteen and forty-five. About 90 percent of the individuals diagnosed with lupus are women. African-American women are about three times more likely to develop lupus, and it is also more common in Hispanic, Asian and American Indian women. Symptoms may include extreme fatigue, painful and swollen joints, unexplained fever, skin rash, and kidney problems. Lupus can lead to arthritis, kidney failure, heart and lung inflammation, central nervous system abnormalities, inflammation of the blood vessels, and blood disorders. For more information on lupus, visit the Lupus Foundation of America at www.lupus.org, or the National Institute of Arthritis and Musculoskeletal and Skin Diseases at www.niams.nih.gov.
GlaxoSmithKline is one of the world’s leading research-based pharmaceutical and healthcare companies, and is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For more information, visit GlaxoSmithKline on the World Wide Web at www.gsk.com.
About Human Genome Sciences
The mission of HGS is to apply great science and great medicine to bring innovative drugs to patients with unmet medical needs.
The HGS clinical development pipeline includes novel drugs to treat hepatitis C, lupus, anthrax disease, cancer, rheumatoid arthritis and HIV/AIDS. The Company’s primary focus is rapid progress toward the commercialisation of its two lead compounds, Albuferon® for hepatitis C, and LymphoStat-B® for lupus. Phase 3 clinical trials of both compounds are now underway.
In June 2006, HGS announced that the U.S. Government exercised its option under an existing contract to purchase 20,000 doses of ABthrax™ for the treatment of anthrax disease. Other HGS drugs in clinical development include three TRAIL receptor antibodies for the treatment of hematopoietic and solid malignancies, in addition to an antibody to the CCR5 receptor for the treatment of HIV/AIDS.
For more information about HGS, please visit the Company’s web site at www.hgsi.com. For more information on LymphoStat-B (belimumab), visit www.hgsi.com/products/LSB.html. Health professionals or patients interested in LymphoStat-B clinical trials or other studies involving HGS products may inquire via the Contact Us section of the company’s web site, www.hgsi.com/products/request.html, or by calling us at (301) 610-5790, extension 3550.
HGS, Human Genome Sciences, ABthrax, Albuferon, BLyS and LymphoStat-B are trademarks of Human Genome Sciences, Inc.
GlaxoSmithKline Forward-Looking Statements
Under the safe harbor provisions of the US Private Securities Litigation Reform Act of 1995, the company cautions investors that any forward-looking statements or projections made by the company, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Factors that may affect the Group's operations are described under 'Risk Factors' in the Operating and Financial Review and Prospects in the company's Annual Report on Form 20-F for 2005.
This announcement contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. The forward-looking statements are based on Human Genome Sciences’ current intent, belief and expectations. These statements are not guarantees of future performance and are subject to certain risks and uncertainties that are difficult to predict. Actual results may differ materially from these forward-looking statements because of the Company’s unproven business model, its dependence on new technologies, the uncertainty and timing of clinical trials, the Company’s ability to develop and commercialize products, its dependence on collaborators for services and revenue, its substantial indebtedness and lease obligations, its changing requirements and costs associated with planned facilities, intense competition, the uncertainty of patent and intellectual property protection, the Company’s dependence on key management and key suppliers, the uncertainty of regulation of products, the impact of future alliances or transactions and other risks described in the Company’s filings with the Securities and Exchange Commission. In addition, the Company will continue to face risks related to animal and human testing, to the manufacture of ABthrax and to FDA concurrence that ABthrax meets the requirements of the ABthrax contract. If the Company is unable to meet the product requirements associated with the ABthrax contract, the U.S. Government will not be required to reimburse the Company for the costs incurred or to purchase any ABthrax doses. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of today’s date. Human Genome Sciences undertakes no obligation to update or revise the information contained in this announcement whether as a result of new information, future events or circumstances or otherwise.
SOURCE: GlaxoSmithKline PLC