Human Genome Sciences Announces Presentation of Additional Phase 3 SLE Study Results for BENLYSTA (Belimumab) at International Congress on SLE

Fri Jun 25, 2010 4:00pm IST

* Reuters is not responsible for the content in this press release.

http://www.businesswire.com/news/home/20100625005117/en

ROCKVILLE, Md.--(Business Wire)--
Human Genome Sciences, Inc. (Nasdaq:HGSI) today announced the presentation of
additional results from BLISS-76, one of two pivotal Phase 3 trials of BENLYSTA
(belimumab) in seropositive patients with systemic lupus erythematosus (SLE).
The additional data will be presented in Vancouver at the 9th International
Congress on Systemic Lupus Erythematosus on Friday and Saturday, June 25-26. 

"The BLISS-76 Phase 3 results presented at the International Congress on SLE
include new data showing that belimumab treatment, consistent with its mechanism
of action, resulted in selective and significantly greater reductions in levels
of B-cell and plasma B-cell subsets, with significant preservation of memory
B-cells," said William W. Freimuth, M.D., Ph.D., Vice President, Clinical
Research - Immunology, Rheumatology and Infectious Diseases, HGS. "Importantly,
belimumab did not significantly affect the ability of SLE patients to maintain a
protective response to vaccines, a finding that is consistent with the
preservation of memory B-cells." 

KEY BLISS-76 FINDINGS PRESENTED AT THE INTERNATIONAL CONGRESS ON SLE

BLISS-76 Patient Response Rates (SRI)

BLISS-76 data recently presented at the 2010 Congress of the European League
Against Rheumatism (EULAR) demonstrated that belimumab 10 mg/kg plus standard of
care met the primary endpoint of the Phase 3 study by achieving a statistically
significant improvement in patient response rate as measured by the SLE
Responder Index (SRI) at Week 52, compared with placebo plus standard of care.
At Week 76, belimumab plus standard of care also showed higher response rates
compared with placebo plus standard of care as measured by SRI; however, this
major secondary endpoint did not reach statistical significance.

* The SRI 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. 
* Post hoc exploratory analyses of BLISS-76 data at Weeks 52 and 76 evaluated
SRI response using greater SELENA SLEDAI reductions (-5, -6, -7, -8, -9 and -10
points) than the 4-point reduction used for the primary endpoint. Using these
higher SELENA SLEDAI thresholds, a greater treatment effect was observed, with
significant improvements in SRI response for the 10 mg/kg treatment group at
both Week 52 and Week 76 (p<0.05 vs. placebo). New data will be presented at the
International Congress on SLE from analyses of SRI response using SELENA SLEDAI
reductions of -8, -9, and - 10 points (included below).

                                                                                                                                     
                     SRI Rate at Week 52                                       SRI Rate at Week 76                                   
 SELENA              Placebo            1 mg/kg            10 mg/kg      Placebo            1 mg/kg            10 mg/kg  
 SLEDAI              N=275              N=271              N=273         N=275              N=271              N=273     
 ≥4-point            33.5%              40.6%              43.2%*        32.4%              39.1%              38.5%     
 reduction                                                                                                               
 ≥5-point            20.4%              31.0%**            32.6%***      21.8%              28.4%              30.8%*    
 reduction                                                                                                               
 ≥6-point            18.9%              28.8%**            30.8%**       20.4%              26.9%              28.9%*    
 reduction                                                                                                               
 ≥7-point            13.4%              19.4%              21.3%*        13.9%              21.7%*             21.8%*    
 reduction                                                                                                               
 N=649                                                                                                                   
 ≥8-point            13.3%              18.5%              21.4%*        12.9%              19.9%*             21.9%**   
 reduction****                                                                                                           
 N=631                                                                                                                   
 ≥9-point            8.2%               14.0%              15.4%         4.8%               14.7%**            15.4%**   
 reduction****                                                                                                           
 N=440                                                                                                                   
 ≥10-point           8.6%               13.9%              15.4%         5.0%               14.6%**            14.0%*    
 reduction****                                                                                                           
 N=420                                                                                                                   
                                                                                                                         


* p<0.05** p<0.01*** p<0.001**** New data

B-Cell Subsets

Belimumab acts by specifically recognizing, binding to, and inhibiting the
biological activity of the naturally occurring protein BLyS (B-lymphocyte
stimulator). 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 cells. The presence of autoantibodies
appears to correlate with disease severity. In the BLISS-76 study, belimumab
treatment resulted in selective and, vs. placebo, significantly greater median
percent reductions in levels of B-cell and plasma B-cell subsets, with
preservation of memory B-cells. The median percent changes from baseline
included the following:

* Greater reductions in CD20+ cells were observed at Week 8 in both belimumab
treatment groups, reached statistical significance by Week 24 and increased
through Week 52 and Week 76 (all p<0.0001 for both belimumab doses vs. placebo).

* Significantly greater reductions in CD20+/CD27- naïve cells were observed at
Week 8 in both belimumab treatment groups and increased through Weeks 24, 52 and
76 (all p<0.0001 for both belimumab doses vs. placebo). 
* Greater reductions in CD20+/CD69+ activated cells were observed at Week 24 in
both belimumab treatment groups, reached statistical significance for belimumab
10 mg/kg by Week 52 which was maintained through Week 76, and reached
significance for belimumab 1 mg/kg by Week 76 (all p<0.05 vs. placebo). 
* Greater reductions in CD20+/CD138+ plasmacytoid cells were observed at Week 8
in both belimumab treatment groups, reached statistical significance by Week 24
(p<0.05, vs. placebo), and increased or were maintained through Weeks 52
(p<0.001 vs. placebo) and 76 (p<0.001 and p<0.01 for belimumab 10 mg/kg and 1
mg/kg respectively vs. placebo). 
* A significantly greater reduction in CD20-/CD138+ plasma cells was observed at
Week 8 in the belimumab 10 mg/kg group, which was maintained through Weeks 24,
52 and 76 (all p<0.01 vs. placebo). In the belimumab 1 mg/kg group, the greater
reduction reached statistical significance by Week 24 (p<0.05 vs. placebo);
however, statistical significance for the lower dose was not maintained through
Weeks 52 and 76). 
* A significantly greater reduction in CD20-/CD27BR short-lived plasma cells was
observed at Week 8 in the belimumab 10 mg/kg group, which was maintained through
Weeks 24, 52 and 76 (all p<0.01 vs. placebo). Greater reductions were also
observed In the belimumab 1 mg/kg group, but the difference did not reach
statistical significance. 
* A significantly greater reduction in CD19+/CD27 BR/CD38BR SLE subset cells was
observed at Week 8 in the belimumab 10 mg/kg group (p<0.01 vs. placebo), which
was maintained through Weeks 24, 52 and 76 (all p<0.001 vs. placebo). Greater
reductions were also observed In the belimumab 1 mg/kg group, but the difference
did not reach statistical significance. 
* Significantly greater increases in CD20+/CD27+ memory cells were observed at
Week 8 in both belimumab treatment groups and increased through Weeks 24, 52 and
76 (p<0.0001 at Weeks 8, 24 and 52, and p<0.05 at Week 76 for belimumab 10 mg/kg
vs. placebo).

Effect on Protective Immune Response

* Belimumab did not significantly affect the ability of SLE patients to maintain
a protective response to pneumococcal, tetanus and influenza vaccines, which is
consistent with the preservation of memory B-cells.

Safety

* In BLISS-76 through 76 weeks, belimumab was generally well tolerated, with
rates of adverse events overall, 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 29.0% of patients on
belimumab and 26.2% of patients on placebo. Infections were reported in 74.3% of
patients on belimumab and 69.1% of patients on placebo. Serious and/or severe
infections were reported in 7.7% of patients on belimumab and 8.4% 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 7.5% in the belimumab treatment groups and 8.4% in the
placebo treatment group. A total of seven malignancies were reported in
BLISS-76: 2, 4, and 1 in the belimumab 10 mg/kg, belimumab 1 mg/kg and placebo
groups, respectively. A total of three deaths were reported in the study: 1, 2,
and 0 in the belimumab 10 mg/kg, belimumab 1 mg/kg and placebo groups,
respectively.

About the BENLYSTA (belimumab) Phase 3 Development Program

The Phase 3 development program for belimumab included 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. Both BLISS-52 and BLISS-76 have
now been completed. 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 randomized and treated 819 patients at 136 clinical sites in 19
countries, primarily in North America and Europe. 

The design of the two trials was similar, but the duration of therapy in the two
studies was different - 52 weeks for BLISS-52 and 76 weeks for BLISS-76. The
data from the BLISS-76 Phase 3 study were analyzed after 52 weeks in accord with
the study protocol, in support of the BLA and MAA submissions. The BLISS-76
study then continued for an additional 24 weeks through the full 76-week
treatment period, with the objective of generating additional information about
belimumab based on a variety of secondary endpoints. 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. 

About BENLYSTA (belimumab)

Belimumab is an investigational human monoclonal antibody drug that specifically
recognizes 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 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 suggest that belimumab can reduce autoantibody levels in SLE.
The results of two pivotal Phase 3 trials, BLISS-52 and BLISS-76, suggest that
belimumab can reduce SLE disease activity. 

In June 2010, GSK submitted a Marketing Authorization Application to the
European Medicines Agency, seeking approval to market belimumab in Europe for
treatment of autoantibody-positive patients with SLE, and HGS submitted a
Biologics License Application (BLA) to the U.S. Food and Drug Administration
seeking approval to market belimumab in the United States. No new drug for lupus
has been approved by regulatory authorities in more than 50 years. 

About the Collaboration with GlaxoSmithKline PLC (GSK)

In 2006, HGS and GSK entered into a definitive co-development and
commercialization agreement under which HGS is conducting the belimumab 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 Systemic Lupus Erythematosus

Systemic lupus erythematosus (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. No new drug for lupus has been approved by
regulatory authorities in more than 50 years. 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.lupus-europe.org. 

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 lupus, inhalation anthrax,
hepatitis C and cancer. 

For more information about HGS, please visit the Company`s web site at
www.hgsi.com. Health professionals and patients interested in clinical trials of
HGS products may inquire via e-mail to medinfo@hgsi.com or by calling HGS at
(877) 822-8472. 

HGS, Human Genome Sciences and BENLYSTA are trademarks of Human Genome Sciences,
Inc. Other trademarks referenced are the property of their respective owners. 

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 Human Genome
Sciences` unproven business model, its dependence on new technologies, the
uncertainty and timing of clinical trials and regulatory approvals, Human Genome
Sciences` 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 facilities,
intense competition, the uncertainty of patent and intellectual property
protection, Human Genome Sciences` 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 SEC. 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.
Media Contact:
Jerry Parrott
Vice President, Corporate Communications
301-315-2777
or
Investor Contact:
Peter Vozzo
Senior Director, Investor Relations
301-251-6003 

Copyright Business Wire 2010