Human Genome Sciences Reports Results of a Phase 2 Clinical Trial of LymphoStat-B(TM) in Patients With Rheumatoid Arthritis
ROCKVILLE, Md., April 6 /PRNewswire-FirstCall/ — Human Genome Sciences, Inc. announced today that LymphoStat-B(TM) (belimumab) has met the primary efficacy and safety endpoints in a Phase 2 clinical trial in patients with rheumatoid arthritis. The Phase 2 study results show that LymphoStat-B(TM) is safe and well tolerated, biologically active, and reduces the signs and symptoms of rheumatoid arthritis at a level of statistical significance.
(Logo: http://www.newscom.com/cgi-bin/prnh/20010612/HGSLOGO )
The double-blind, placebo-controlled, multi-center Phase 2 clinical trial was designed to evaluate the safety, optimal dosing, and efficacy of LymphoStat-B, a human monoclonal antibody to B-lymphocyte stimulator (BLyS(TM)), in patients with rheumatoid arthritis.(1-2) The study was conducted in the United States and Poland. A total of 283 patients with active moderate-to-severe rheumatoid arthritis who had failed prior treatment were enrolled and randomized to receive one of three different doses (1, 4 or 10 mg/kg) of LymphoStat-B or placebo administered intravenously over a 24-week treatment period, in addition to standard-of-care therapy. All patients in the study were dosed on Days 0, 14 and 28, then every 28 days for the remainder of the 24 weeks. The study design included concurrent standard-of- care therapy, including up to two disease-modifying anti-rheumatic drugs and up to 10 mg/day of prednisone. Approximately 73% of study participants were receiving background methotrexate therapy. Approximately 38% of study participants had failed at least one TNF-alpha inhibitor. Efficacy was evaluated according to the American College of Rheumatology (ACR) criteria for defining clinical improvement in rheumatoid arthritis patients. The primary efficacy endpoint for the LymphoStat-B Phase 2 study was the rate of ACR 20 response at Week 24 (i.e., the percentage of patients who achieved at least 20% improvement on the ACR-specified measures of disease activity).(3) Secondary biological endpoints, as well as safety, were also evaluated.
Results show that LymphoStat-B is well tolerated with no clinically significant differences from placebo in adverse events, serious adverse events or laboratory abnormalities. Clinically significant infusion reactions were rare. Patients treated with LymphoStat-B showed statistically significant improvement in the primary efficacy endpoint versus the placebo group. The rate of ACR 20 response at Week 24 was 36% in the 1-mg/kg active-treatment cohort, and 31% in all active-treatment groups combined — significantly higher than the 17% rate of improvement observed for the placebo group (p=0.011 and p=0.02, respectively). In addition, trends toward a drug benefit were observed in the 4-mg/kg treatment group (28% ACR 20 response, p=0.13) and in the 10-mg/kg treatment group (29% ACR 20 response, p=0.088). As anticipated based on preclinical and clinical research to date(4-7), results demonstrate that LymphoStat-B produced statistically significant reductions in all active-treatment arms in both circulating B cells (CD 20+ and other subsets) and rheumatoid factor, versus placebo. Human Genome Sciences will continue to collect data from the current Phase 2 trial of LymphoStat-B in patients with rheumatoid arthritis through an ongoing optional extension protocol.
David C. Stump, M.D., Executive Vice President, Drug Development, said, “These results confirm and extend the observations made in our Phase 1 study of LymphoStat-B in patients with systemic lupus erythematosus. I am particularly encouraged that LymphoStat-B achieved its primary efficacy endpoint in the context of a protocol design that included heterogeneous background standard-of-care therapy for all patients enrolled in the trial. The relatively low placebo response rate suggests that this was a somewhat refractory population to treat. The results add substantively to the evidence of LymphoStat-B’s biological activity, as demonstrated by statistically significant reductions in levels of circulating CD 20+ and other B-cell subsets, and in rheumatoid factor autoantibody levels. Very importantly, the data also show that LymphoStat-B was safe and well tolerated during this 24- week exposure period. We intend to meet soon with our clinical experts, our potential partner and regulatory authorities to discuss the appropriate next steps in the development of LymphoStat-B for the treatment of rheumatoid arthritis. I look forward to the full presentation of these data at an appropriate scientific meeting later this year, and to the availability of data from our Phase 2 trial in systemic lupus erythematosus, which we anticipate having this Fall.”(8)
H. Thomas Watkins, Chief Executive Officer, said, “Autoimmune diseases such as lupus and rheumatoid arthritis cause suffering to millions of people. I am pleased by the positive outcome of the Phase 2 trial of LymphoStat-B in rheumatoid arthritis and by the growing evidence of LymphoStat-B’s biological activity. Completion of this study marks the achievement of a key 2005 milestone for Human Genome Sciences. The next milestone for LymphoStat-B is completion of the Phase 2 trial in systemic lupus erythematosus, which we expect to achieve in the Fall. Our hope is that LymphoStat-B will one day become an important treatment option for patients afflicted by lupus, rheumatoid arthritis and other autoimmune diseases.”
Several million people worldwide have rheumatoid arthritis. It is a systemic, chronic autoimmune disease characterized by inflammation of the membrane lining the joint. Symptoms typically appear during middle age and may include swelling of the joints, difficulty moving, and daily joint pain that frequently interferes with a person’s ability to conduct normal activities.
LymphoStat-B is a human monoclonal antibody that specifically recognizes and inhibits the biological activity of B-lymphocyte stimulator, or BLyS. BLyS is a naturally occurring protein discovered by Human Genome Sciences that is required for the development of B-lymphocyte cells into mature plasma B cells.(9-10) Plasma B cells produce antibodies, the body’s first line of defense against infection. Retrospective and prospective studies have shown elevated levels of BLyS in the blood of many patients with systemic lupus erythematosus, and in the blood and joint fluid of patients with rheumatoid arthritis. In lupus, rheumatoid arthritis, and certain other autoimmune diseases, elevated levels of B-lymphocyte stimulator (BLyS) are believed to contribute to the production of autoantibodies — antibodies that attack and destroy the body’s own healthy tissues.(9-21) The presence of autoantibodies, especially rheumatoid factor, appears to correlate with disease severity.(22- 23) Preclinical and clinical studies demonstrate that B-cell antagonists can reduce autoantibody levels and help control autoimmune disease activity.(4-7), (24-25)
LymphoStat-B is a Human Genome Sciences drug, created through a collaboration with Cambridge Antibody Technology.
For more information on LymphoStat-B, see http://www.hgsi.com/products/LSB.html. For more information on rheumatoid arthritis, lupus, or autoimmune diseases, visit the Arthritis Foundation at http://www.arthritis.org/, the National Institute of Arthritis and Musculoskeletal and Skin Diseases at http://www.niams.nih.gov/, or The Lupus Foundation of America at http://www.lupus.org/.
For additional information on Human Genome Sciences, please visit our web site at http://www.hgsi.com/.
Health professionals or patients interested in inquiring about LymphoStat- B trials or any other study involving HGSI products are encouraged to inquire via the Contact Us section of the Human Genome Sciences web site, http://www.hgsi.com/products/request.html, or by calling us at 301-610-5790, extension 3550.
Human Genome Sciences is a company with the mission to treat and cure disease by bringing new gene-based protein and antibody drugs to patients.
HGS, Human Genome Sciences, BLyS and LymphoStat-B are trademarks of Human Genome Sciences, Inc.
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. 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.
Footnotes:
1. (HGSI Press Release) Human Genome Sciences Completes Patient
Enrollment in a Phase 2 Clinical Trial of LymphoStat-B for the
Treatment of Rheumatoid Arthritis. July 29, 2004.
2. (HGSI Press Release) Human Genome Sciences Initiates Phase 2 Clinical
Trial of LymphoStat-B for the Treatment of Rheumatoid Arthritis.
January 8, 2004.
3. American College of Rheumatology (ACR) Subcommittee on Rheumatoid
Arthritis Guidelines. Guidelines for the management of rheumatoid
arthritis: 2002 update. Arthritis & Rheumatism 2002; 46(2):328-346.
4. (HGSI Press Release) Human Genome Sciences Reports Results of Phase 1
Clinical Trial of LymphoStat-B in Patients with Systemic Lupus
Erythematosus. October 28, 2003.
5. Furie R, Stohl W, Ginzler E, et al. Safety, pharmacokinetic and
pharmacodynamic results of a Phase 1 single and double dose-
escalation study of LymphoStat-B (human monoclonal antibody to BLyS)
in SLE patients. 67th Annual Scientific Meeting of the American
College of Rheumatology/Association of Rheumatology Health
Professionals. October 26, 2003. Abstract # 922.
6. Halpern W, Lappin P, Zanardi T, et al. Effects of LymphoStat-B, a
BLyS antagonist, when administered intravenously to cynomolgus
monkeys. 67th Annual Scientific Meeting of the American College of
Rheumatology/Association of Rheumatology Health Professionals.
October 27, 2003. Abstract # 1537.
7. Baker KP, Edwards BM, Main SH et al. Generation and characterization
of LymphoStat-B, a human monoclonal antibody that antagonizes the
bioactivities of B-Lymphocyte Stimulator. Arthritis & Rheumatism
2003; 48: 3253-3265.
8. (HGSI Press Release) Human Genome Sciences Completes Patient
Enrollment in a Phase 2 Clinical Trial of LymphoStat-B for the
Treatment of Systemic Lupus Erythematosus. July 29, 2004.
9. (HGSI Press Release) Human Genome Sciences Announces the Discovery of
a Novel Immune Stimulant. July 8, 1999.
10. Moore PA, Belvedere O, Orr A, et al. BLyS: member of the tumor
necrosis factor family and B lymphocyte stimulator. Science. 1999;
285: 260-263.
11. Tan S, Roschke V, Perry JW, Arkfeld DG, Ehresmann GR, Migone T,
Hilbert DM, and Stohl W. Local production of B lymphocyte stimulator
and APRIL in arthritic joints of patients with inflammatory
arthritis. Arthritis & Rheumatism April 2003; 48(4): 982-992.
12. Carter RH. A role for BLyS in tissue inflammation? Arthritis &
Rheumatism April 2003; 48(4): 882-885.
13. Cheema GS, Roschke V, Hilbert DM and Stohl W. Elevated serum B
lymphocyte stimulator levels in patients with systemic immune-based
rheumatic diseases. Arthritis & Rheumatism June 2001; 44(6): 1313-
1319.
14. Wang H, Marsters SA, Baker T, et al. TACI-ligand interactions are
required for T cell activation and collagen-induced arthritis in
mice. Nature Immunol. 2001; 2: 632-637.
15. Gross J, Dillon S, Mudri S, et al. TACI-Ig neutralizes molecules
critical for B cell development and autoimmune disease. Impaired B
cell maturation in mice lacking BLyS. Immunity 2001 15(2): 289-302.
16. (HGSI Press Release) High Levels of BLyS Implicated in Lupus and
Rheumatoid Arthritis Patients. October 30, 2000.
17. Gross JA, Johnston J, Mudri S, et al. TACI and BCMA are receptors
for a TNF homologue implicated in B-cell autoimmune disease. Nature.
2000; 404: 995-999.
18. Khare S.D., Saarosi I, Xia XZ, et al. Severe B cell hyperplasia and
autoimmune disease in TALL-1 transgenic mice. Proc Natl Acad Sci
USA. 2000; 97: 3370-3375.
19. MacKay F., Woodcock SA, Lawton P, et al. Mice transgenic for BAFF
develop lymphocytic disorders along with autoimmune manifestations.
J. Exp. Med. 1999; 190: 1697-1710.
20. Petri M, Stohl W, Chatham W, et al. BLyS plasma concentrations
correlate with disease activity and levels of anti-dsDNA
autoantibodies and immunoglobulins (IgG) in a SLE patient
observational study. 67th Annual Scientific Meeting of the American
College of Rheumatology/Association of Rheumatology Health
Professionals. October 27, 2003. Abstract #1712.
21. Petri M. Biomarkers in SLE: The Hopkins lupus cohort. Lupus
Foundation of America Biomarkers for the Assessment of Systemic Lupus
Erythematosus Meeting. March 2003.
22. Knijff-Dutmer E, et al. Rheumatoid factor measured by
fluoroimmunoassay: a responsive measure of rheumatoid arthritis
disease activity that is associated with joint damage. Annals of
Rheumatoid Disease. 2002; 61: 603-607.
23. Bukhari M, et al. Rheumatoid factor is the major predictor of
increasing severity of radiographic erosions in rheumatoid arthritis.
Arthritis & Rheumatism. 2002; 46(4): 906-912.
24. Tsokos, G. B-cells, be gone – B-cell depletion in the treatment of
rheumatoid arthritis. New England Journal of Medicine. 2004;
350(25): 2546-2548.
25. Edwards JCW, Szczepanski L, Szechinski J, et al. Efficacy of B-cell-
targeted therapy with rituximab in patients with rheumatoid
arthritis. New England Journal of Medicine. 2004; 350(25): 2572-
2581.
Photo: http://www.newscom.com/cgi-bin/prnh/20010612/HGSLOGOAP Archive: http://photoarchive.ap.org/PRN Photo Desk, photodesk@prnewswire.com
Human Genome Sciences, Inc.
CONTACT: Jerry Parrott, Vice President, Corporate Communications,+1-301-315-2777, or Kate de Santis, Director, Investor Relations,+1-301-251-6003, both of Human Genome Sciences, Inc.
Web site: http://www.hgsi.com/http://www.hgsi.com/products/LSB.htmlhttp://www.arthritis.org/http://www.niams.nih.gov/http://www.lupus.org/
Company News On-Call: http://www.prnewswire.com/comp/121115.html