BENLYSTA™ (belimumab)

BENLYSTA is an investigational human monoclonal antibody drug and the first in a new class of drugs called BLyS-specific inhibitors. It is being developed for the treatment of systemic lupus erythematosus (SLE) by HGS and GlaxoSmithKline (GSK) under a co-development and commercialization agreement entered into in August 2006. [1-2] BENLYSTA has successfully met its primary endpoint in two pivotal Phase 3 trials in systemic lupus. [3-6] Following discussions with regulatory authorities, HGS and GSK plan to submit marketing applications in the United States, Europe and other regions in the first half of 2010. HGS believes BENLYSTA has the potential to become the first new approved drug for people living with lupus in more than 50 years.

How BENLYSTA Works

BENLYSTA inhibits the biological activity of B-lymphocyte stimulator, or BLyS®. BLyS is a naturally occurring protein discovered by HGS [7-8], which is required for the survival and 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 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 results of prospective observational studies show a significant correlation of elevated levels of BLyS with SLE disease activity. [9-16]

BENLYSTA acts by: (1) specifically recognizing and binding to BLyS, (2) inhibiting BLyS’s stimulation of B-cell development, and (3) restoring the potential for autoantibody-producing B cells to undergo the normal process of apoptosis (programmed cell death). Preclinical and clinical studies show that BLyS antagonists such as BENLYSTA can reduce autoantibody levels in SLE. [9-53] The results of two pivotal Phase 3 trials show that belimumab can reduce SLE disease activity. [3-6]

BENLYSTA Inhibits the Biological Activity of BLyS

benlysta_biological_activity.gif

Figure 1. BENLYSTA (belimumab) specifically binds to and inhibits the biological activity of BLyS. Preclinical and clinical results to date show that BENLYSTA can reduce the levels of circulating B cells, including precursor cells to the plasma B cells that produce the body’s normal and abnormal antibodies. This suggests that BENLYSTA may prove useful in the treatment of lupus and certain other autoimmune diseases.


Collaboration with GlaxoSmithKline

In August 2006, HGS and GSK entered into a co-development and commercialization agreement under which HGS has responsibility for conducting the BENLYSTA 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. [1-2]

Potential Treatment Settings

HGS and GSK are working closely together to develop BENLYSTA (belimumab) as a potential new treatment for systemic lupus erythematosus (SLE) and other autoimmune diseases. SLE is a chronic, life-threatening autoimmune disease. Approximately five million people worldwide, including approximately 1.5 million in the United States, suffer from various forms of lupus, including SLE.

Lupus can occur at any age, but appears mostly in young people ages 15 to 45. About 90 percent of those 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, the Lupus Research Institute at www.lupusresearchinstitute.org, the National Institute of Arthritis and Musculoskeletal and Skin Diseases at www.niams.nih.gov, or Lupus Europe at www.elef.rheumanet.org.

BLyS in Patients with Autoimmune Disease

 
lsb_clip_image001_0001.jpg

Figure 2. In healthy people, the body signals autoantibody-producing B cells to kill themselves through apoptosis. In patients with autoimmune diseases, such as lupus, the BLyS protein stimulates B-cell hyperactivity and inhibits apoptosis. This allows autoantibody-producing B cells to mature and release autoantibodies into the body. Autoantibodies then attack the body’s own tissues, causing autoimmune diseases like lupus.


Phase 3 Clinical Development Program

The Phase 3 development program for belimumab includes two double-blind, placebo-controlled, multi-center Phase 3 superiority trials – BLISS-52 and BLISS-76 – to evaluate the efficacy and safety of belimumab plus standard of care, versus placebo plus standard of care, in seropositive (HEp-2 ANA > 1:80 and/or anti-dsDNA > 30 IU/mL) patients with SLE. [54-57] This is the largest clinical trial program ever conducted in lupus patients. BLISS-52 randomized and treated 865 patients at 90 clinical sites in 13 countries, primarily in Asia, South America and Eastern Europe. BLISS-76 enrolled and randomized 826 patients at 133 clinical sites in 19 countries, primarily in North America and Europe. The design of the two trials is similar, but the duration of therapy in the two studies is different – 52 weeks for BLISS-52 and 76 weeks for BLISS-76. HGS designed the Phase 3 program for belimumab in collaboration with GSK and leading international SLE experts, and the program is being conducted under a Special Protocol Assessment agreement with FDA [57].

The primary efficacy endpoint of BLISS-52 and BLISS-76 is the patient response rate at Week 52 based on the SLE Responder Index, which is defined by: (1) a reduction from baseline of at least 4 points on the SELENA SLEDAI disease activity scale (which indicates a clinically important reduction in SLE disease activity); (2) no worsening of disease as measured by the Physician’s Global Assessment (worsening defined as an increase of 0.30 points or more from baseline); (3) no new BILAG A organ domain score (which indicates a severe flare of lupus disease activity) and no more than one new BILAG B organ domain score (which indicates a moderate flare of disease activity). Analysis for the primary endpoint is based on intention-to-treat (ITT) and adjusted for baseline stratification factors, including SELENA SLEDAI score, proteinuria and race. The data from BLISS-76 were analyzed after 52 weeks in support of a potential Biologics License Application in the United States and Marketing Authorization Applications in Europe and other regions. However, the trial is ongoing and will continue for another 24 weeks.

In each of the two Phase 3 trials, patients were randomized to one of three treatment groups: 10 mg/kg belimumab (BLISS-52, n=290), 1 mg/kg belimumab (BLISS-52, n=288), or placebo (BLISS-52, n=287). Patients are dosed intravenously on Days 0, 14 and 28, then every 28 days thereafter for the duration of the study. All patients receive standard of care therapy in addition to the study medication. Safety is reviewed by an independent Data Monitoring Committee throughout both studies.

In October 2006, HGS received a Special Protocol Assessment from the FDA, agreeing that the design of the Phase 3 program and clinical trials is suitable to support regulatory approval. [57] HGS also met with the European Agency for the Evaluation of Medicinal Products (EMEA), and received agreement from EMEA on the major components of the Phase 3 program, including the primary efficacy endpoint measures, target patient population, and dose selection.

Clinical Progress to Date

BENLYSTA (belimumab) has met the primary efficacy endpoint in two pivotal Phase 3 trials, as specified by Special Protocol Assessment agreement with FDA. [3-6] The efficacy of treatment with BENLYSTA plus standard of care was superior to placebo plus standard of care in both BLISS-52 and BLISS-76, with overall adverse event rates comparable to placebo plus standard of care. HGS and GSK plan to submit marketing applications in the first half of 2010, following discussions with regulatory authorities in the United States, Europe and other regions.

BLISS-52


In July 2009, HGS and GSK announced that BENLYSTA met the primary endpoint in BLISS-52, the first of two pivotal Phase 3 trials in seropositive patients with SLE. [4] The results of BLISS-52, which were presented in full in October 2009 at the 73rd Annual Scientific Meeting of the American College of Rheumatology (ACR) [5-6], demonstrated that belimumab plus standard of care achieved a clinically and statistically significant improvement in patient response rate as measured by the SLE Responder Index at Week 52, compared with placebo plus standard of care. Study results also showed that belimumab was generally well tolerated, with adverse event rates comparable between belimumab and placebo treatment groups.

Among 865 patients randomized and treated, belimumab met its primary efficacy endpoint by achieving a superior SLE patient response rate at Week 52 vs. placebo plus standard of care.

Among 865 patients randomized and treated, belimumab met its primary efficacy endpoint by achieving a superior SLE patient response rate at Week 52 vs. placebo plus standard of care.

  • A clinically and statistically significant improvement was shown in patient response rate for belimumab plus standard of care vs. placebo plus standard of care: 57.6% for 10 mg/kg belimumab, 51.4% for 1 mg/kg belimumab, and 43.6% for placebo (p=0.0006 and p=0.013 for 10 mg/kg and 1 mg/kg belimumab, respectively).
  • The BLISS-52 patient response rate was based on the SLE Responder Index (SRI), which defines patient response by an improvement in SELENA SLEDAI score of 4 points or greater, with no clinically significant BILAG worsening, and no clinically significant worsening in Physician’s Global Assessment.
  • There were more responders in the 10 mg/kg belimumab group compared to the placebo group between Weeks 4 and 8 of the study and this difference was statistically significant at Week 16 (p<0.05 for 10 mg/kg belimumab vs. placebo). The improvement was statistically significant and sustained for 10 mg/kg and 1 mg/kg belimumab from Week 24 and Week 28, respectively, through 52 weeks (p<0.05 for both belimumab treatment groups).
  • The improvement in patient response rate was generally consistent across subgroups.
  • A dose response trend was observed, with a greater rate of patient response in the 10 mg/kg belimumab dose group.
  • Results for each individual component of the SRI strongly support the overall improvement shown for the primary endpoint.

Key findings of the BLISS-52 study also included the following:

FLARES

  • Belimumab significantly delayed time to first SLE disease flare versus placebo (SLE Flare Index/SFI): median = 119 days for 10 mg/kg belimumab, 126 days for 1 mg/kg belimumab, and 84 days for placebo (p=0.0036 and p=0.0026 for 10 mg/kg and 1 mg/kg belimumab, respectively vs. placebo). 
  • The risk of having severe SLE disease flares (SFI) was reduced over 52 weeks by 43% in the 10 mg/kg belimumab treatment group and by 24% in the 1 mg/kg belimumab treatment group vs. placebo (p=0.0055 and p=0.1342 for 10 mg/kg and 1 mg/kg belimumab, respectively). 
  • The risk of having 1 BILAG A (severe flare) or more than 1 BILAG B (moderate flare) organ domain score was reduced by 42% in the 10 mg/kg belimumab treatment group and by 13% in the 1 mg/kg treatment group vs. placebo (p=0.0016 and p=0.3722 for 10 mg/kg and 1 mg/kg belimumab, respectively).  

DISEASE ACTIVITY

  • A significantly greater percentage of patients receiving belimumab achieved a reduction in SELENA SLEDAI score of at least 4 points by Week 52 (p=0.0024 and p=0.019 for 10 mg/kg and 1 mg/kg belimumab, respectively, vs. placebo), with improvement observed for 10 mg/kg belimumab within 4-8 weeks and reaching statistical significance at Week 16 and Weeks 24-52 (p<0.05 vs. placebo). 
  • A significantly greater improvement in Physician’s Global Assessment (PGA) at Week 52 was observed in the belimumab treatment groups, with a mean percentage change from baseline of 45.7% for 10 mg/kg belimumab, 39.3% for 1 mg/kg belimumab, and 27.8% for placebo (p<0.0001 and p=0.004 for 10 mg/kg and 1 mg/kg belimumab, respectively, vs. placebo). The improvement in PGA was observed within 4-8 weeks and was sustained through 52 weeks (p<0.05 for both belimumab treatment groups).

STEROID USE

  • In patients who were receiving >7.5 mg per day of prednisone at baseline, a significantly higher percentage of patients in the 1 mg/kg belimumab treatment group vs. the placebo group had their average prednisone dose reduced by at least 25% from baseline to 7.5 mg per day or less during the last 12 weeks of study (p=0.025). A higher percentage of patients in the 10 mg/kg belimumab treatment group vs. the placebo group also had their average prednisone dose reduced by at least 25% from baseline to 7.5 mg per day or less during the last 12 weeks of study, but the difference did not reach a level of statistical significance (p=0.053).
  • In patients who were receiving <7.5 mg per day of prednisone at baseline, significantly fewer patients in the 10 mg/kg belimumab treatment group vs. the placebo group increased their prednisone use to >7.5 mg per day during the last 20 weeks of study (p<0.05). Fewer increases in prednisone use also were observed in the 1 mg/kg belimumab treatment group vs. the placebo group during the last 20 weeks of study, but the difference did not reach a level of statistical significance.

FATIGUE AND QUALITY OF LIFE

  • Improved fatigue scores were observed in the 10 mg/kg belimumab treatment group vs. the placebo group within 4-8 weeks, and both belimumab treatment groups achieved statistically significant improvement of fatigue by Week 52 (FACIT-Fatigue Scale; p<0.05 for both belimumab groups vs. the placebo group). 
  • Improvement in health-related quality of life (HRQOL) as measured by the SF-36 Physical Component Summary (PCS) score at Week 24, a prespecified major secondary endpoint, was not significantly different among treatment groups. HRQOL improvement as measured by the SF-36 PCS score at Week 52 was significantly greater in both belimumab treatment groups vs. the placebo group (p=0.025 for 10 mg/kg and p=0.027 for 1 mg/kg belimumab, respectively).

SAFETY

  • In BLISS-52, belimumab was generally well tolerated, with rates of overall adverse events, serious adverse events, infections and fatalities comparable between belimumab and placebo treatment groups. Serious infections were reported in 5.9% of patients on placebo and 6.1% of patients on belimumab. The most common adverse events were headache, arthralgia, upper respiratory tract infections, urinary tract infection and influenza, and were also comparable between belimumab and placebo treatment groups. No malignancies were reported.

BLISS-76


In November 2009, HGS and GSK announced that BENLYSTA met the primary endpoint in BLISS-76, the second of two pivotal Phase 3 trials in seropositive patients with SLE. [3] BLISS-76 topline study results through 52 weeks showed that belimumab 10 mg/kg plus standard of care achieved a statistically significant improvement in patient response rate as measured by the SLE Responder Index at Week 52, compared with placebo plus standard of care. Study results also showed that belimumab was generally well tolerated, as demonstrated by a similar rate of discontinuations due to adverse events across treatment groups, with overall adverse event rates comparable between belimumab and placebo treatment groups.

The data from the BLISS-76 study were analyzed after 52 weeks, in accord with the study protocol, in support of a potential Biologics License Application in the United States and Marketing Authorization Applications in Europe and other regions. However, the BLISS-76 study is ongoing and will continue for 24 more weeks. Additional data will be available following completion of the full 76-week study period.

Topline BLISS-76 results include the following:

Based on an intention-to-treat (ITT) analysis, belimumab 10 mg/kg met its primary efficacy endpoint of superiority versus placebo at Week 52. A statistically significant improvement was shown in patient response rate for belimumab 10 mg/kg plus standard of care, vs. placebo plus standard of care, as measured by the SLE Responder Index at Week 52: 43.2% for 10 mg/kg belimumab, 40.6% for 1 mg/kg belimumab, and 33.8% for placebo (p=0.021 and p=0.10 for 10 mg/kg and 1 mg/kg belimumab, respectively vs. placebo). The 1 mg/kg dose plus standard of care did not achieve statistically significant improvement in the current study. The SLE Responder Index defines patient response as an improvement in SELENA SLEDAI score of 4 points or greater, with no clinically significant BILAG worsening and no clinically significant worsening in Physician’s Global Assessment.

Results for prespecified major secondary efficacy endpoints in BLISS-76 were:

  • The proportion of patients with a reduction in SELENA SLEDAI score of at least 4 points by Week 52, was 46.9% for belimumab 10 mg/kg, 42.8% for belimumab 1 mg/kg, and 35.6% for placebo (p=0.0062 and p=0.087 for belimumab 10 mg/kg and 1 mg/kg, respectively vs. placebo). 
  • Improvement from baseline in Physician’s Global Assessment (PGA) at Week 24 was not statistically different between the belimumab and placebo treatment groups. Mean improvement in PGA at Week 52, a prespecified although not a major secondary endpoint, was 0.49 for belimumab 10 mg/kg, 0.55 for belimumab 1 mg/kg, and 0.46 for placebo (p=0.12 for belimumab 10 mg/kg and p=0.022 for 1 mg/kg, respectively vs. placebo). 
  • At entry into the BLISS-76 study, approximately 46% of patients were receiving steroids at a prednisone-equivalent dose of at least 7.5 mg per day. Among these patients, the percentage of patients who had their average steroid dose reduced by at least 25% from baseline to 7.5 mg per day or less during the last 12 weeks of study was 16.7% for belimumab 10 mg/kg, 19.2% for belimumab 1 mg/kg, and 12.7% for placebo (not statistically significant vs. placebo). 
  • Improvement in health-related quality of life at Week 24 as measured by the SF-36 Physical Component Summary (PCS) score was not significantly different among treatment groups. Mean improvement in the SF-36 PCS score at Week 52, a prespecified although not a major secondary endpoint, was 3.41 for belimumab 10 mg/kg, 4.37 for belimumab 1 mg/kg, and 2.85 for placebo (p=0.51 for belimumab 10 mg/kg and p=0.012 for 1 mg/kg, respectively vs. placebo).

In BLISS-76, belimumab was generally well tolerated, with rates of overall adverse events, serious and/or severe adverse events, all infections, serious and/or severe infections, and discontinuations due to adverse events comparable between treatment groups receiving belimumab plus standard of care and the treatment group receiving placebo plus standard of care.

Serious and/or severe adverse events were reported in 26.8% of patients on belimumab and 24.0% of patients on placebo. Infections were reported in 72.1% of patients on belimumab and 67.3% of patients on placebo. Serious and/or severe infections were reported in 7.2% of patients on belimumab and 8.0% of patients on placebo. Serious and/or severe infusion reactions were reported in 1.1% of patients on belimumab and 0.7% of patients on placebo. Discontinuations due to adverse events were 7.2% in the belimumab treatment groups and 7.6% in the placebo treatment group. Malignancies were reported by 2, 3, and 1 subjects in the belimumab 10 mg/kg, belimumab 1 mg/kg and placebo groups, respectively. There were three deaths in the study, with 1, 2, and 0 reported in the belimumab 10 mg/kg, belimumab 1 mg/kg and placebo groups, respectively.

Long-Term Phase 2 Continuation Study Results


Results through four years of the long-term Phase 2 continuation study of belimumab were presented in October 2009 at the ACR Annual Scientific Meeting [20] The data showed that belimumab was associated with sustained improvement or stabilization of SLE disease activity and patient response rates and with decreased frequency of SLE disease flares in seropositive patients through four years of treatment.

The evidence of sustained clinical effect from Week 52 to Week 208 in seropositive patients were treated with belimumab from initiation of the Phase 2 study included an increase from 46% at Week 52 to 57% at Week 208 in the percentage achieving the patient response rate selected as the Phase 3 primary efficacy endpoint. The overall incidence of adverse events (in general and by system organ class), serious adverse events, infections, serious infections, malignancies and laboratory abnormalities decreased or stabilized over time from Week 52 to Week 208.

How BENLYSTA Was Discovered

HGS first discovered the naturally occurring protein, BLyS or B-lymphocyte stimulator, in 1997 and published a preliminary description of its activity in the journal, Science, in July 1999. [7-8] Following that discovery, HGS initiated a program to develop human monoclonal antibodies that would specifically recognize and inhibit the biological activity of BLyS. BENLYSTA is a human monoclonal antibody that HGS generated through a collaboration with Cambridge Antibody Technology. [61]

For More Information about BENLYSTA Clinical Trials

Health professionals and patients interested in BENLYSTA (belimumab) clinical trials or other studies involving HGS products may inquire via email to This e-mail address is being protected from spam bots, you need JavaScript enabled to view it or by calling HGS at (877) 822-8472. Information about HGS clinical trials may also be found at www.clinicaltrials.gov.

Footnotes

  1. (HGSI Press Release) GlaxoSmithKline Exercises Option to LymphoStat-B. July 7, 2005. 
  2. (HGSI Press Release) Human Genome Sciences Completes Enrollment in First of Two Phase 3 LymphoStat-B Trials. April 22, 2008. 
  3. (HGSI Press Release) Human Genome Sciences and GlaxoSmithKline Announce Positive Results in Second of Two Phase 3 Trials of BENLYSTA in Systemic Lupus Erythematosus. November 2, 2009. 
  4. (HGSI and GSK Joint Press Release) Human Genome Sciences and GlaxoSmithKline Announce Full Presentation at ACR of Positive Phase 3 Study Results for BENLYSTA in Systemic Lupus Erythematosus. October 20, 2009. 
  5. Navarra S, Guzman R, Gallacher A, et al. Belimumab, a BLyS-specific inhibitor, reduced disease activity, flares and prednisone use in patients with active SLE: efficacy and safety results from the Phase 3 BLISS-52 study. 73rd Annual Scientific Meeting of the American College of Rheumatology. October 20, 2009. Oral Presentation. 
  6. (HGSI and GSK Joint Press Release) Human Genome Sciences and GlaxoSmithKline Announce Positive Phase 3 Study Results for BENLYSTA in Systemic Lupus Erythematosus. July 20, 2009. 
  7. 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. 
  8. (HGSI Press Release) Human Genome Sciences Announces the Discovery of a Novel Immune Stimulant. July 8, 1999. 
  9. 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 an SLE patient observational study. 67th Annual Scientific Meeting of the American College of Rheumatology/Association of Rheumatology Health Professionals. October 27, 2003. Abstract #1712. 
  10. Carter RH. A role for BLyS in tissue inflammation? Arthritis & Rheumatism April 2003; 48(4): 882-885. 
  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. Petri M. Biomarkers in SLE: The Hopkins lupus cohort. Lupus Foundation of America biomarkers for the assessment of systemic lupus erythematosus meeting. March 2003. 
  13. Zhang J, Roschke V, Baker K, Kimberly R, et al. Cutting edge: A role for B lymphocyte stimulator in systemic lupus erythematosus. J Immuno. 2001; 166:6-10. 
  14. 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. 
  15. 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. 
  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 SD, 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. Petrie MA, Furie RA, Merrill JT, Freimuth WW, et al. Four-year experience of belimumab, a BlyS-specific inhibitor, in systemic lupus erythematosus. 73rd Annual Scientific Meeting of the American College of Rheumatology. October 21, 2009. Oral Presentation. 
  21. (HGSI Press Release) Human Genome Sciences Reports Positive Long-Term Data for BENLYSTA (formerly LymphoStat-B) in Patients with Active Systemic Lupus Erythematosus. June 11, 2009. 
  22. Merrill JT, Furie R, Wallace DJ, Freimuth W, et al. 4 year experience of belimumab, a fully human monoclonal antibody, in the treatment of systemic lupus erythematosus (SLE). Annual Congress of the European League Against Rheumatism (EULAR 2009). June 11, 2009. Poster presentation. 
  23. (HGSI Press Release) Human Genome Sciences Reports Sustained Improvement Through Three Years on Treatment with LymphoStat-B in Patients with Active Systemic Lupus Erythematosus. June 12, 2008. 
  24. Furie R, Petri M, Weisman MH, Freimuth W, et al. Belimumab improved or stabilized SLE disease activity and reduced flare rates during 3 years of therapy. Annual Congress of the European League Against Rheumatism (EULAR 2008). June 12, 2008. Oral presentation. 
  25. Merrill JT, Wallace DJ, McKay J, Freimuth W, et al. Long-term safety profile belimumab (fully human monoclonal antibody to BLyS) in patients with systemic lupus erythematosus (SLE). Annual Congress of the European League Against Rheumatism (EULAR 2008). June 12, 2008. Poster presentation. 
  26. Chatham W, Aranow C, Furie R, Freimuth W, et al. Progressive normalization of autoantibody, immunoglobulin, and complement levels over 3 years of belimumab (fully human monoclonal antibody to BLyS) therapy in systemic lupus erythematosus (SLE) patients. Annual Congress of the European League Against Rheumatism (EULAR 2008). June 12, 2008. Poster presentation. 
  27. Ginzler EM, Wallace DJ, Chatham W, Freimuth W, et al. Belimumab (fully human monoclonal antibody to BLyS) reduced steroid use in systemic lupus erythematosus (SLE) patients during 3 years of therapy. Annual Congress of the European League Against Rheumatism (EULAR 2008). June 12, 2008. Poster presentation. 
  28. (HGSI Press Release) Human Genome Sciences Reports Positive Data from Long-Term Treatment with LymphoStat-B in Patients with Active Systemic Lupus Erythematosus. November 9, 2007. 
  29. Petri M, Furie R, Ginzler E, Freimuth W, et al. Belimumab improved or stabilized SLE disease activity and reduced flare rate over 2.5 years of therapy. 71st Annual Scientific Meeting of the American College of Rheumatology. November 9, 2007. Oral presentation. 
  30. Merrill JT, Wallace DJ, Stohl W, Freimuth W, et al. Safety profile of belimumab (fully human monoclonal antibody to BLyS) in patients with systemic lupus erythematosus (SLE) treated during a placebo-controlled trial and in a long-term continuation study. 71st Annual Scientific Meeting of the American College of Rheumatology. November 8, 2007. Poster presentation. 
  31. Stohl W, Chatham W, McKay J, Freimuth W, et al. Progressive normalization of autoantibody, immunoglobulin, and complement levels over 2.5 years of belimumab (fully human monoclonal antibody to BLyS) therapy in systemic lupus erythematosus (SLE) patients. 71st Annual Scientific Meeting of the American College of Rheumatology. November 8, 2007. Poster presentation. 
  32. (HGSI Press Release) Human Genome Sciences Reports that a Phase 2 Study of LymphoStat-B Showed Significant Reductions in Disease Activity in Patients with Active Systemic Lupus Erythematosus. June 14, 2007. 
  33. Ginzler G, Furie R, Wallace DJ, et al. Novel combined response endpoint shows that belimumab (fully human monoclonal antibody to B-lymphocyte stimulator [BLyS]) improves or stabilizes SLE disease activity in a Phase 2 trial. Annual Congress of the European League Against Rheumatism (EULAR 2007). June 14, 2007. Oral presentation. 
  34. Chatham W, Stohl W, Merrill JT, et al. Changes in circulating B cell subtype counts, antibody levels and immunoglobulins that associate with therapeutic responsiveness in SLE to BLyS protein antagonism by belimumab. Annual Congress of the European League Against Rheumatism (EULAR 2007). June 16, 2007. Poster presentation. 
  35. Strand V, Crawford B, Petri M, et al. Responders defined by SELENA SLEDAI, BILAG and Physicians Global Assessment of disease activity report stabilization and/or improvement in health-related quality of life (HRQOL) following treatment with belimumab. Annual Congress of the European League Against Rheumatism (EULAR 2007). June 16, 2007. Poster presentation. 
  36. Strand V, Petri M, Buyon J, et al. Systemic lupus erythematosus (SLE) impacts all domains of health-related quality of life (HRQOL): baseline results from five randomized controlled trials (RCTS). Annual Congress of the European League Against Rheumatism (EULAR 2007). June 16, 2007. Poster presentation. 
  37. (HGSI Press Release) Human Genome Sciences Announces Positive 76-Week Results of Phase 2 Clinical Trial of LymphoStat-B in Systemic Lupus Erythematosus. November 14, 2006. 
  38. Wallace DJ, Lisse J, Stohl W, Freimuth W, et al. Belimumab reduces SLE disease activity and demonstrates durable bioactivity at 76 weeks. 70th Annual Scientific Meeting of the American College of Rheumatology. November 14, 2006. 
  39. Stohl W, Wallace DJ, Merrill JT, et al. Changes in circulating B-cell counts, autoantibody levels and immunoglobulins that associate with therapeutic responsiveness in SLE to BLyS protein antagonism by belimumab. 70th Annual Scientific Meeting of the American College of Rheumatology. November 14, 2006.
  40. Furie R, Lisse J, Merrill JT, Petri M, Ginzler E, Freimuth W, et al. Belimumab (fully human monoclonal antibody to B-lymphocyte stimulator [BLyS]) improves or stabilizes SLE activity in a multi-center Phase 2 trial. 70th Annual Scientific Meeting of the American College of Rheumatology. November 12, 2006. 
  41. Strand V, Crawford, B, Petri M, et al. Patients with active systemic lupus erythematosus (SLE) treated with belimumab improve health-related quality of life (HRQOL) in a randomized controlled trial (RCT). 70th Annual Scientific Meeting of the American College of Rheumatology. November 12, 2006. 
  42. Strand V, Crawford, B, Petri M, et al. Therapeutic responses reflecting a reduction in SELENA SLEDAI score are associated with a stabilization or improvement in health-related quality of life (HRQOL). 70th Annual Scientific Meeting of the American College of Rheumatology. November 12, 2006. 
  43. Strand V, Petri M, Buyon J, et al. Baseline data from five controlled trials (RCTs) demonstrate that systemic lupus erythematosus (SLE) impacts all domains of health-related quality of life (HRQOL). 70th Annual Scientific Meeting of the American College of Rheumatology. November 12, 2006. 
  44. Huizinga, TW, Boling E, Valente R, et al. Genetic and environmental risk factors, disease outcome and responses to anti B-cell therapy belimumab indicate anti-CCP positive RA is a distinct disease entity. 70th Annual Scientific Meeting of the American College of Rheumatology. November 13, 2006. 
  45. (HGSI Press Release) Human Genome Sciences Announces Full Presentation of Results of Phase 2 Clinical Trial of LymphoStat-B in Systemic Lupus Erythematosus. June 22, 2006. 
  46. Wallace DJ, Lisse J, Stohl W, McKay J, et al. Belimumab (LymphoStat-B) shows bioactivity and reduces SLE disease activity. Annual Congress of the European League Against Rheumatism (EULAR 2006). June 22, 2006. Oral Presentation #0029. 
  47. Furie R, Lisse J, Merrill JT, Petri M, et al. Multiple SLE disease activity measures in a multi-center Phase 2 SLE trial demonstrate belimumab improves or stabilizes SLE activity in serologically active SLE patients. Annual Congress of the European League Against Rheumatism (EULAR 2006). June 22, 2006. Oral Presentation #0030. 
  48. Petri M, Wallace DJ, Stohl W, McKay J, et al. SLE patients with active production of anti-nuclear autoantibodies (ANA positive) have distinct patterns of lupus activity and peripheral B-cell biomarkers compared to ANA negative patients. Annual Congress of the European League Against Rheumatism (EULAR 2006). June 23, 2006. Abstract #FRI0231. 
  49. (HGSI Press Release) Human Genome Sciences Reports Phase 2 Results for LymphoStat-B (Belimumab) in Patients with Rheumatoid Arthritis. November 17, 2005. 
  50. McKay J, Chwalinska-Sadowska H, Boling E, et al. Belimumab, a fully human monoclonal antibody to B-lymphocyte stimulator (BLyS), combined with standard of care therapy reduces the signs and symptoms of rheumatoid arthritis in a heterogeneous subject population. 69th Annual Scientific Meeting of the American College of Rheumatology. November 16, 2005. Oral Presentation #1920. 
  51. (HGSI Press Release) Results of Phase 1 Clinical Trial Demonstrate that LymphoStat-B Is Safe and Biologically Active in Patients with Systemic Lupus Erythematosus. April 21, 2003 
  52. 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. October 27, 2003. Abstract # 1537. 
  53. Sekut L, Sturm B, Poortman C, Wager R, Zhang C, Abramian D, Riccobene T, Sosnovtseva S, Sung C, Roschke V, Baker KP, Hilbert DM. Characterization of a human monoclonal antibody that antagonizes B-lymphocyte stimulator bioactivities. 65th Annual Scientific Meeting of the American College of Rheumatology (2001). Abstract 1377. 
  54. (HGSI Press Release) Human Genome Sciences Announces Phase 3 Clinical Development Program for LymphoStat-B in Systemic Lupus Erythematosus. August 9, 2006. 
  55. (HGSI Press Release) Human Genome Sciences and GlaxoSmithKline Initiate Second Phase 3 Clinical Trial of LymphoStat-B in Systemic Lupus Erythematosus. May 30, 2007. 
  56. (HGSI Press Release) Human Genome Sciences and GlaxoSmithKline Announce Initiation of Phase 3 Clinical Trial of LymphoStat-B in Systemic Lupus Erythematosus. February 13, 2007. 
  57. (HGSI Press Release) Human Genome Sciences Announces Special Protocol Assessment and Agreement from FDA for Phase 3 Clinical Trials of LymphoStat-B in Systemic Lupus Erythematosus. October 26, 2006. 
  58. (HGSI Press Release) Novel Evidence-Based Systemic Lupus Erythematosus (SLE) Responder Index Described in Peer Reviewed Publication as Potentially Significant Advance in Lupus Drug Development. September 4, 2009. 
  59. Furie RA, Petrie MA, Wallace DJ, Freimuth WW, et al. Novel evidence-based systemic lupus erythematosus responder index. Arthritis Care & Research. September 15, 2009. 
  60. (HGSI Press Release) Human Genome Sciences Announces Selection of LymphoStat-B for Participation in FDA’s Continuous Marketing Application Pilot 2 Program. March 4, 2004. 
  61. (HGSI Press Release) Human Genome Sciences and Cambridge Antibody Technology Commit to Exclusive Development of Anti-BLyS Antibodies. October 30, 2000. .

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Furie RA, Petrie MA, Wallace DJ, Freimuth WW, et al. Novel evidence-based systemic lupus erythematosus responder index. Arthritis Care & Research. September 15, 2009.

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Ginzler G, Furie R, Wallace DJ, et al. Novel combined response endpoint shows that belimumab (fully human monoclonal antibody to B-lymphocyte stimulator [BLyS]) improves or stabilizes SLE disease activity in a Phase 2 trial. Annual Congress of the European League Against Rheumatism (EULAR 2007). June 14, 2007. Oral presentation.

Ginzler EM, Wallace DJ, Chatham W, Freimuth W, et al. Belimumab (fully human monoclonal antibody to BLyS) reduced steroid use in systemic lupus erythematosus (SLE) patients during 3 years of therapy. Annual Congress of the European League Against Rheumatism (EULAR 2008). June 12, 2008. Poster presentation.

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.

Huizinga, TW, Boling E, Valente R, et al. Genetic and environmental risk factors, disease outcome and responses to anti B-cell therapy belimumab indicate anti-CCP positive RA is a distinct disease entity. 70th Annual Scientific Meeting of the American College of Rheumatology. November 13, 2006.

McKay J, Chwalinska-Sadowska H, Boling E, et al. Belimumab, a fully human monoclonal antibody to B-lymphocyte stimulator (BLyS), combined with standard of care therapy reduces the signs and symptoms of rheumatoid arthritis in a heterogeneous subject population. 69th Annual Scientific Meeting of the American College of Rheumatology. November 16, 2005. Oral Presentation #1920.

Merrill JT, Furie R, Wallace DJ, Freimuth W, et al. 4 year experience of belimumab, a fully human monoclonal antibody, in the treatment of systemic lupus erythematosus (SLE). Annual Congress of the European League Against Rheumatism (EULAR 2009). June 11, 2009. Poster presentation.

Merrill JT, Wallace DJ, Stohl W, Freimuth W, et al. Safety profile of belimumab (fully human monoclonal antibody to BLyS) in patients with systemic lupus erythematosus (SLE) treated during a placebo-controlled trial and in a long-term continuation study. 71st Annual Scientific Meeting of the American College of Rheumatology. November 8, 2007. Poster presentation.

Merrill JT, Wallace DJ, McKay J, Freimuth W, et al. Long-term safety profile belimumab (fully human monoclonal antibody to BLyS) in patients with systemic lupus erythematosus (SLE). Annual Congress of the European League Against Rheumatism (EULAR 2008). June 12, 2008. Poster presentation.

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.

Nardelli B, Belvedere O, Roschke V, Moore PA, Olsen HS, Migone TS, Sosnovtseva S, Carrell JA, Feng P, Giri JG, Hilbert DM. Synthesis and release of B-lymphocyte stimulator from myeloid cells. Blood 2001 Jan 1; 97(1):198-204.

Navarra S, Guzman R, Gallacher A, et al. Belimumab, a BLyS-specific inhibitor, reduced disease activity, flares and prednisone use in patients with active SLE: efficacy and safety results from the Phase 3 BLISS-52 study. 73rd Annual Scientific Meeting of the American College of Rheumatology. October 20, 2009. Oral Presentation.

Petrie MA, Furie RA, Merrill JT, Freimuth WW, et al. Four-year experience of belimumab, a BlyS-specific inhibitor, in systemic lupus erythematosus. 73rd Annual Scientific Meeting of the American College of Rheumatology. October 21, 2009. Oral Presentation. 

Petri M. Biomarkers in SLE : The Hopkins lupus cohort. Lupus Foundation of America Biomarkers for the Assessment of Systemic Lupus Erythematosus Meeting. March 2003.  

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.

Petri M, Wallace DJ, Stohl W, McKay J, et al. SLE patients with active production of anti-nuclear autoantibodies (ANA positive) have distinct patterns of lupus activity and peripheral B-cell biomarkers compared to ANA negative patients. Annual Congress of the European League Against Rheumatism (EULAR 2006). June 23, 2006. Abstract #FRI0231.

Petri M, Furie R, Ginzler E, Freimuth W, et al. Belimumab improved or stabilized SLE disease activity and reduced flare rate over 2.5 years of therapy. 71st Annual Scientific Meeting of the American College of Rheumatology. November 9, 2007. Oral presentation.

Sekut L, Sturm B, Poortman C, Wager R, Zhang C, Abramian D, Riccobene T, Sosnovtseva S, Sung C, Roschke V, Baker KP, Hilbert DM. Characterization of a human monoclonal antibody that antagonizes B-lymphocyte stimulator bioactivities. American College of Rheumatology 2001 Annual Meeting, Abstract 1377.

Stohl W, Wallace DJ, Merrill JT, et al. Changes in circulating B-cell counts, autoantibody levels and immunoglobulins that associate with therapeutic responsiveness in SLE to BLyS protein antagonism by belimumab. 70th Annual Scientific Meeting of the American College of Rheumatology. November 14, 2006.

Stohl W, Chatham W, McKay J, Freimuth W, et al. Progressive normalization of autoantibody, immunoglobulin, and complement levels over 2.5 years of belimumab (fully human monoclonal antibody to BLyS) therapy in systemic lupus erythematosus (SLE) patients. 71st Annual Scientific Meeting of the American College of Rheumatology. November 8, 2007. Poster presentation.

Strand V, Crawford, B, Petri M, et al. Patients with active systemic lupus erythematosus (SLE) treated with belimumab improve health-related quality of life (HRQOL) in a randomized controlled trial (RCT). 70th Annual Scientific Meeting of the American College of Rheumatology. November 12, 2006.

Strand V, Crawford, B, Petri M, et al. Therapeutic responses reflecting a reduction in SELENA SLEDAI score are associated with a stabilization or improvement in health-related quality of life (HRQOL). 70th Annual Scientific Meeting of the American College of Rheumatology. November 12, 2006.

Strand V, Petri M, Buyon J, et al. Baseline data from five controlled trials (RCTs) demonstrate that systemic lupus erythematosus (SLE) impacts all domains of health-related quality of life (HRQOL). 70th Annual Scientific Meeting of the American College of Rheumatology. November 12, 2006.

Strand V, Petri M, Buyon J, et al. Systemic lupus erythematosus (SLE) impacts all domains of health-related quality of life (HRQOL): baseline results from five randomized controlled trials (RCTS). Annual Congress of the European League Against Rheumatism (EULAR 2007). June 16, 2007. Poster presentation.

Strand V, Crawford B, Petri M, et al. Responders defined by SELENA SLEDAI, BILAG and Physicians Global Assessment of disease activity report stabilization and/or improvement in health-related quality of life (HRQOL) following treatment with belimumab. Annual Congress of the European League Against Rheumatism (EULAR 2007). June 16, 2007. Poster presentation.

Tan S, Roschke V, Perry JW, Arkfeld DG, Ehresmann GR, Migone T, Hilbert DM, 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.

Wallace DJ, Lisse J, Stohl W, Freimuth W, et al. Belimumab reduces SLE disease activity and demonstrates durable bioactivity at 76 weeks. 70th Annual Scientific Meeting of the American College of Rheumatology. November 14, 2006.

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Wu Y, Bressette D, Carrell JA et al. Tumor necrosis factor (TNF) receptor superfamily member TACI Is a high affinity receptor for TNF family members APRIL and BLyS. J. Biol. Chem. 2000; 275(45): 35478—35485

Zhang J, Roschke V, Baker K, Kimberly R, et al. Cutting edge: A role for B lymphocyte stimulator in systemic lupus erythematosus. J Immuno. 2001; 166:6-10.

Non-HGS, Non-Collaborators

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.

Cambridge G, Leandro MJ, Edwards JCW, Ehrenstein MR, Salden M, and Webster D. B lymphocyte depletion in patients with rheumatoid arthritis: Serial studies of immunological parameters. American College of Rheumatology 2002 Annual Meeting, Abstract 1350.

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.

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.

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.

Khare SD, 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.

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.

Leandro MJ, Edwards JCW, Cambridge G. Clinical outcome in 22 patients with rheumatoid arthritis treated with B lymphocyte depletion. Ann Rheum Dis 2002; 61: 883-888.

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.

Schiemann B, Gommerman JL, Vora K, Cachero TG, Shulga-Morskaya S, Dobles M, Frew E, Scott ML. An essential role for BAFF in the normal development of B cells through a BCMA-independent pathway. Science. 14 September, 2001 ; 293: 2111-2114.

Schneider P, MacKay F, Steiner V, Hofmann K, Bodmer JL, Holler N, Ambrose C, Lawton P, Bixler S, Acha-Orbea H, Valmori D, Romero P, Werner-Favre C, Zubler RH, Browning JL, Tschopp J. BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth. J. Exp Med 1999 Jun 7; 189(11): 1747-56.

Thompson JS, Bixler SA, Qian F, Vora K, Scott ML, Cachero TG, Hession C, Schneider P, Sizing ID, Mullen C, Strauch K, Zafari M, Benjamin CD, Tschopp J, Browning JL, Ambrose C. BAFF-R, a Novel TNF Receptor That Specifically Interacts with BAFF. Science. 14 September 2001 ; 293: 2108-2111.

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.

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.

Xia XZ, Treanor J, Senaldi G, et al. TACI is a TRAF-interacting receptor for TALL-1, a tumor necrosis factor family member involved in B cell regulation. J. Exp. Med. 2000; 192: 137-143.

Yan M, Wang H, Chan B, et al. Activation and accumulation of B cells in TACI-deficient mice. Nature Immunology. 2000; 2: 638-643.

To view announcements on LymphoStat-B and BLyS, click on the following:

Human Genome Sciences and GlaxoSmithKline Announce Positive Results in Second of Two Phase 3 Trials of BENLYSTA in Systemic Lupus Erythematosus - November 2, 2009:

Human Genome Sciences and Glaxosmithkline Announce Full Presentation at ACR of Positive Phase 3 Study Results For BENLYSTA™ in Systemic Lupus Erythematosus - October 20, 2009

Novel Evidence-Based Systemic Lupus Erythematosus (SLE) Responder Index Described in Peer Reviewed Publication as Potentially Significant Advance in Lupus Drug Development - September 4, 2009

Human Genome Sciences And Glaxosmithkline Announce Positive Phase 3 Study Results For Benlysta™ In Systemic Lupus Erythematosus - July 20, 2009

Human Genome Sciences Reports Positive Long-Term Data for BENLYSTA™ (formerly Lymphostat-B®) in Patients with Active Systemic Lupus Erythematosus -June 11, 2008 

Human Genome Sciences Completes Enrollment in Second Phase 3 Lymphostat-B® Trial -August 27, 2008 

Human Genome Sciences Reports Positive Long-Term Data for LymphoStat-B in Patients with Active Systemic Lupus Erythematosus - June 12, 2008

Human Genome Sciences Completes Enrollment in First of Two Phase 3 LymphoStat-B® Trials - April 22, 2008

Human Genome Sciences Reports Positve Data from Long-Term Treatment with LymphoStat-B in Patients with Active Systemic Lupus Erythematosus - November 9. 2007

Human Genome Sciences Reports that a Phase 2 Study of Lymphostat-B® Showed Significant Reductions in Disease Activity in Patients with Active Systemic Lupus Erythematosus - June 14, 2007

Human Genome Sciences and GlaxoSmithKline Initiate Second Phase 3 Clinical Trial of LymphoStat-B® in Systemic Lupus Erythematosus - May 30, 2007

Human Genome Sciences and Glaxosmithkline Announce Initiation of Phase 3 Clinical Trial of Lymphostat-B® in Systemic Lupus Erythematosus - February 13, 2007

Human Genome Sciences Announces Positive Special Protocol Assessment from FDA for Phase 3 Clinical Trials of Lymphostat-B™ in Systemic Lupus Erythematosus - November 14, 2006

Human Genome Sciences Announces Positive Special Protocol Assessment from FDA for Phase 3 Clinical Trials of Lymphostat-B™ in Systemic Lupus Erythematosus - October 26, 2006

Human Genome Sciences Announces Phase 3 Clinical Development Program for Lymphostat-B™ in Systemic Lupus Erythematosus - August 9, 2006

Human Genome Sciences Announces Full Presentation of Results of Phase 2 Clinical Trial of Lymphostat-B™ in Systemic Lupus Erythematosus - June 22, 2006

Human Genome Sciences Reports Phase 2 Results for Lymphostat-B™ (Belimumab) in Patients with Rheumatoid Arthritis - November 17, 2005

Human Genome Sciences Reports Results of a Phase 2 Clinical Trial of LymphoStat-B™ in Patients with Systemic Lupus Erythematosus - October 5, 2005

GlaxoSmithKline Exercises Option to LymphoStat-B™ - July 7, 2005

Human Genome Sciences Reports Results of a Phase 2 Clinical Trial of LymphoStat-B™ in Patients with Rheumatoid Arthritis - April 6, 2005

Human Genome Sciences Completes Patient Enrollment in a Phase 2 Clinical Trial of Lymphostat-B™ for the Treatment of Rheumatoid Arthritis - July 29, 2004

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

Human Genome Sciences Announces Selection of Lymphostat-BTM for Participation in FDA's Continuous Marketing Application Pilot 2 Program - March 4, 2004

Human Genome Sciences Initiates Phase 2 Clinical Trial of Lymphostat-BTM for the Treatment of Rheumatoid Arthritis - January 8, 2004

Human Genome Sciences Reports Results of Phase 1 Clinical Trial of Lymphostat-B™ in Patients With Systemic Lupus Erythematosus - October 28, 2003

Human Genome Sciences Initiates Phase 2 Clinical Trial of LymphoStat-B for the Treatment of Systemic Lupus Erythematosus - September 25, 2003

Results of Phase I Clinical Trial Demonstrate That LymphoStat-B is Safe and Biolocically Active in Patients with Systemic Lupus Erythematosus - April 21, 2003

Human Genome Sciences Initiates Trials of a New Drug for Systemic Lupus Erythematosus and Other Autoimmune Diseases - November 1, 2001

Human Genome Sciences Announces Trial For Treatment of Immunoglobulin-A Deficiency - September 19, 2001

Human Genome Sciences Receives Orphan Drug Designation for BLyS Therapeutic Protein for Treatment of Common Variable Immunodeficiency - February 27, 2001

High Levels of BLyS Implicated in Lupus and Rheumatoid Arthritis Patients - October 30, 2000

Human Genome Sciences and Cambridge Antibody Technology Commit to Exclusive Development of Anti-BLyS Antibodies - October 30, 2000

Human Genome Sciences and Dow Agree To Develop HGS' Radiolabeled B-Lymphocyte Stimulator - October 30, 2000

Human Genome Sciences to Initiate Human Clinical Trials of BLyS - June 23, 2000

Human Genome Sciences Announces the Discovery of a Novel Immune Stimulant - July 8, 1999