Human Genome Sciences Announces Positive Special Protocol Assessment From FDA For Phase 3 Clinical Trials Of LymphoStat-B(TM)

Main Category: Lupus
Also Included In: Clinical Trials / Drug Trials
Article Date: 27 Oct 2006 - 0:00 PDT

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Human Genome Sciences, Inc. (Nasdaq: HGSI) today announced that it has received a Special Protocol Assessment from the U.S. Food and Drug Administration (FDA), agreeing to the Company's Phase 3 clinical development program for LymphoStat-B(TM) (belimumab) in patients with active systemic lupus erythematosus (SLE).

"We expect to initiate Phase 3 trials of LymphoStat-B before the end of 2006, and we look forward to moving ahead with site activation and patient enrollment," said H. Thomas Watkins, President and Chief Executive Officer, Human Genome Sciences. "We believe that this novel antibody drug will become an important therapeutic option for patients suffering from SLE. For HGS, advancing LymphoStat-B to late-stage clinical study is a critically important step in our evolution into a commercial organization."

The design of the LymphoStat-B Phase 3 development program includes a primary efficacy endpoint that emerged directly from the previously reported results of a Phase 2 clinical trial. The endpoint is a combined patient response rate that includes elements of the SELENA SLEDAI and BILAG disease activity indices, as well as the Physician's Global Assessment index. These measures are well known to clinical investigators with experience in SLE. The Phase 2 results show that LymphoStat-B, as measured by this combined response rate, significantly reduced disease activity in serologically active patients, the population in which the drug will be studied in Phase 3.

"The positive Special Protocol Assessment received from the FDA leaves no issues outstanding, and provides HGS with confidence that the design of the Phase 3 development program and clinical trials for LymphoStat-B is suitable to support regulatory approval," said Sally D. Bolmer, Ph.D., R.A.C., Senior Vice President, Regulatory Affairs. "The SPA agreement is the latest example of the positive and productive interactions HGS has had with the FDA throughout the development of this product, including its designation as a Fast Track Product, its selection for participation in the Pilot 2 program, and the excellent guidance we received during our end-of-Phase 2 meeting."

HGS previously disclosed that it has met with the European Agency for the Evaluation of Medicinal Products (EMEA), and has received agreement on the major components of the Phase 3 clinical development program, including the primary efficacy endpoint, target patient population, and dose selection. HGS designed the program in collaboration with GlaxoSmithKline (GSK) and leading international SLE experts.

About the Design of the LymphoStat-B Phase 3 Development Program

Under the terms of the Special Protocol Assessment, and as proposed by HGS, the Phase 3 development program for LymphoStat-B will include two double- blind, placebo-controlled, multi-center Phase 3 superiority trials, BLISS-52 and BLISS-76, which will 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. 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.

The total duration of the two studies will differ, at 52 weeks (BLISS-52) and 76 weeks (BLISS-76), respectively. Aside from duration, the two studies will have similar protocols. In each of the two Phase 3 trials, approximately 810 patients will be enrolled and randomized 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. To be eligible for enrollment in the Phase 3 trials, patients must be serologically active, with unequivocal antinuclear antibody (ANA) test results assessed at 2 independent time points (HEp-2 ANA of at least 1:80 and/or anti-dsDNA of at least 30 IU/mL). Background SLE medications must be stable for a period of at least 30 days prior to Day 0.

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.

About the Phase 2 Trial Results Reported in June 2006

In June 2006, HGS reported the full presentation of data from a Phase 2 clinical trial of LymphoStat-B in 449 patients with active SLE. The Phase 2 study was designed as a randomized, double-blind, placebo-controlled, dose- ranging superiority trial to evaluate the safety, tolerability and efficacy of LymphoStat-B plus standard of care, versus placebo plus standard of care. Participants were randomized to receive one of three different doses of LymphoStat-B or placebo (1, 4 or 10 mg/kg) administered intravenously over a 52-week treatment period, in addition to standard-of-care therapy.

The Phase 2 results show that LymphoStat-B produced statistically significant reductions in disease activity versus placebo, exhibited clinically relevant biological activity, and was safe and well tolerated. Among the Phase 2 study findings was a significantly improved response rate among seropositive 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 program design.

About the Collaboration with GSK

In August 2006, HGS and GSK entered into a definitive co-development and co-commercialization 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 commercialized under the agreement.

About LymphoStat-B

LymphoStat-B is a human monoclonal antibody that specifically recognizes and inhibits the biological activity of B-lymphocyte stimulator, or BLyS(TM). 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 is a Human Genome Sciences drug, created 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 Program.

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 States alone. 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 http://www.lupus.org, or the National Institute of Arthritis and Musculoskeletal and Skin Diseases at http://www.niams.nih.gov.

About Human Genome Sciences

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

The HGS clinical development pipeline includes drugs to treat hepatitis C, lupus, anthrax disease, cancer, rheumatoid arthritis and HIV/AIDS. The Company's primary focus is rapid progress toward the commercialization of its two lead compounds, Albuferon(TM) for hepatitis C, and LymphoStat-B(TM) for lupus. Both compounds are expected to advance to Phase 3 clinical trials in 2006.

In June 2006, HGS announced that the U.S. Government exercised its option under an existing contract to purchase 20,000 doses of ABthrax(TM) for the treatment of anthrax disease. Other HGS compounds 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 http://www.hgsi.com. For more information on LymphoStat-B, visit http://www.hgsi.com/products/LSB.html. Health professionals or patients interested in inquiring about LymphoStat-B clinical trials or any other study involving HGS products in development are encouraged to inquire via the Contact Us section of the company's web site, http://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.

SAFE HARBOR STATEMENT

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.

Human Genome Sciences, Inc.
http://www.hgsi.com

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