Human Genome Sciences Announces Positive 76-Week Results of Phase 2 Clinical Trial of LymphoStat-B(TM) in Systemic Lupus Erythematosus
Tuesday November 14, 7:00 am ET
- LymphoStat-B(TM) reduces signs and symptoms of SLE disease and demonstrates durable biological activity at 76 weeks -
- Phase 3 clinical trials to begin before year-end 2006 -
ROCKVILLE, Md., Nov. 14 /PRNewswire-FirstCall/ -- Human Genome Sciences, Inc. (Nasdaq: HGSI - News) announced today that the 76-week results of a Phase 2 clinical trial demonstrated that LymphoStat-B(TM) (belimumab) reduced disease activity in patients with serologically active systemic lupus erythematosus (SLE), exhibited durable biological activity, and appeared safe and well tolerated. In the LymphoStat-B treatment groups, the percentage of serologically active SLE patients who achieved the combined response rate selected as the primary efficacy endpoint for Phase 3 trials of LymphoStat- B(TM) increased from 46% at Week 52 to 56% at Week 76, with no increase in infections or infectious events observed over time.
The results were presented today in two oral presentations in Washington, DC at the 70th Annual Meeting of the American College of Rheumatology/ Association of Rheumatology Health Professionals (ACR/ARHP). Additional LymphoStat-B results were reported in poster presentations throughout the meeting.
"The data that have emerged from the 24-week extension of the Phase 2 trial of LymphoStat-B show continued improvement beyond the first 52 weeks of treatment," said Daniel J. Wallace, M.D., Clinical Professor of Medicine, David Geffen School of Medicine, UCLA (based at Cedars-Sinai Medical Center, Los Angeles). "The reductions we see in SLE biomarkers, as well as the improvements observed in health-related quality of life, appear to correlate with therapeutic response. In serologically active patients, LymphoStat-B significantly reduced SLE disease activity, as evidenced by changes in multiple biomarkers and clinical indicators, including the combined response rate chosen as the primary efficacy endpoint of the Phase 3 trials. We look forward to continuing its evaluation as a potential treatment for SLE."
"The results presented at this year's ACR/ARHP meeting confirm and extend the growing body of evidence that LymphoStat-B has the potential to help meet the significant unmet need that we see in the SLE patient population," said William W. Freimuth, M.D., Ph.D., Vice President, Clinical Research - Immunology, Rheumatology and Infectious Diseases, Human Genome Sciences. "We are encouraged that 96% of the patients who completed the 52-week Phase 2 study chose to participate in the 24-week extension phase. Many of these patients were first randomized into the trial as long as three years ago and continue on treatment today. This provides us with a substantial longitudinal safety data base as we prepare to initiate Phase 3 trials before the end of 2006."
About the Phase 2 Trial Results
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. A total of 449 patients with active SLE 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. Serologically active patients accounted for 72% (323/449) of the total Phase 2 study population. 86% (386/449) of the patients were receiving background prednisone therapy, either alone or in combination. At Week 52, patients were offered the opportunity to participate in an optional 24-week extension phase. In the extension phase, all placebo patients received LymphoStat-B at a dose of 10 mg/kg, while patients in the LymphoStat-B 10 mg/kg treatment arm continued on the 10 mg/kg dose, and patients in the 1 mg/kg and 4 mg/kg LymphoStat-B treatment arms were offered the choice of continuing on the same dose or receiving LymphoStat-B at a dose of 10 mg/kg.
Of the patients who completed 52 weeks of treatment, 96% (351/364) elected to enter the 24-week extension phase of the trial, and 92% (321/351) of those who entered completed it. Of those completing the extension phase, 83% (265/321) continue to receive LymphoStat-B. The study began in October 2003.
In June 2006, HGS reported the full presentation of 52-week data from the Phase 2 trial of LymphoStat-B in patients with SLE. The 52-week results demonstrated that LymphoStat-B significantly reduced disease activity in patients with serologically active SLE, exhibited clinically relevant biological activity, and appeared safe and well tolerated. Among the Phase 2 study findings was a significantly improved response rate among serologically active patients at Week 52, as defined by an improvement in SELENA SLEDAI score of 4 points or greater, no BILAG worsening, and no worsening in Physician's Global Assessment (46% for LymphoStat-B versus 29% for placebo, p<0.01). This combination of measures is the primary efficacy endpoint in the Phase 3 program design.
The data presented at the ACR/ARHP annual meeting demonstrated that LymphoStat-B continued to reduce the signs and symptoms of SLE disease activity throughout the 24-week extension phase of the study, demonstrated durable biological activity at Week 76, and appeared safe and well tolerated, with frequency and severity of adverse events similar to placebo and with no increase at higher doses. The evidence of continuing improvement from Week 52 to Week 76 includes:
-- An increase from 46% to 56% in the response rate among serologically
active patients, as defined by an improvement in SELENA SLEDAI score of
4 points or greater, no worsening in Physician's Global Assessment
(with worsening defined as an increase in PGA of more than 0.30
points), no new BILAG A organ domain score and no more than 1 new BILAG
B organ domain score from baseline. This combination of measures at 52
weeks is the primary efficacy endpoint of the Phase 3 trials.
-- An increase from 29% to 38% in the reduction in SLE disease activity
among serologically active patients, as measured by SELENA SLEDAI.
-- An increase from 33% to 41% among serologically active patients who
showed no worsening in the Physician's Global Assessment.
-- An increase in the mean improvement in health-related quality of life
from 3.0 points to 3.4 points among serologically active patients, as
measured by the SF-36 Physical Component Summary score.
-- A durable reduction in anti-dsDNA autoantibodies (at least 50% or
negative) among patients who were positive for anti-dsDNA at baseline
(27% at Week 52; 28% at Week 76).
-- Durable or increased reductions from Week 52 to Week 76 in B-cell
subsets including total CD20+, naive (CD20+/CD27-), activated
(CD20+/CD69+), and plasmacytoid (CD20+/CD138+).
-- An increase in C4 complement among patients with low C4 complement at
baseline (33% at Week 52; 46% at Week 76).
-- Stable reductions in immunoglobulins, with no increase in infections or
infectious events over time.
In addition, the 52-Week data showed that, in serologically active SLE patients, LymphoStat-B:
-- Significantly delayed the time to SLE flare after six months (p<0.04);
-- Reduced the frequency of SLE flares after six months;
-- Significantly reduced the frequency of patients transitioning from low-
dose prednisone (less than or equal to 7.5 mg/day) to high-dose
prednisone (>7.5 mg/day) (p<0.05 over multiple time-points);
-- Significantly reduced the number of patients experiencing BILAG
Neurological and Musculoskeletal organ domain flares at Week 52
(Neurological p=0.04; Musculoskeletal p<0.01; and Cardiovascular-
Respiratory (p=0.06); and
-- Produced significant and clinically meaningful improvements in health-
related quality of life in serologically active SLE patients.
The 76-week results of the LymphoStat-B Phase 2 trial, as well as the results of other studies presented at the ACR/ARHP meeting, demonstrated that therapeutic responses in patients with active SLE, as measured by the combined response index selected as the primary efficacy endpoint of the LymphoStat-B Phase 3 trials, correlated well with changes in SLE biomarkers and improvements observed in health-related quality of life. In the Phase 2 study, relative to baseline, responders across all groups (LymphoStat-B and placebo) exhibited greater changes in biomarkers for SLE disease and reported more improvement in health-related quality of life than was observed in non- responders.
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 demonstrated 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.
For links to scientific presentations and posters referenced, or for more information about LymphoStat-B, visit hgsi.com. |
