578 - Safety Profile of Belimumab, a B-Lymphocyte Stimulator–Specific Inhibitor, in Phase 2 and 3 Clinical Trials of Patients with Active Systemic Lupus Erythematosus

Sunday, November 6, 2011: 9:00 AM-6:00 PM
Hall F2 - Poster Hall (McCormick Place West)
D.J. Wallace1, S. Navarra2, M. Petri3, A. Gallacher4, R. Gúzman5, M. Thomas6, R.A. Furie7, O. Zamani8, R.A. Levy9, R.F. van Vollenhoven10, S. Cooper11, Z.J. Zhong11, W. Freimuth11, L. Pineda11, R. Cervera12 and BLISS-52 and -76 and LBSL02/99 Study Groups13, 1Cedars-Sinai/UCLA, Los Angeles, CA, 2University of Santo Tomas Hospital, Manila, Philippines, 3Johns Hopkins University School of Medicine, Baltimore, MD, 4Hospital Británico de Buenos Aires, Buenos Aires, Argentina, 5IDEARG, SaludCoop, Bogotá, Colombia, 6Kerala Institute of Medical Sciences, Kerala, India, 7North Shore-LIJ Health System, Lake Success, NY, 8Rheumazentrum Favoriten, Wien, Austria, 9Hospital Universitário Pedro Ernesto, Rio de Janeiro, Brazil, 10The Karolinska Institute, Stockholm, Sweden, 11Human Genome Sciences, Inc., Rockville, MD, 12Hospital Clinic, Barcelona, Spain, 13Multicenter
Presentation Number: 578

Background/Purpose: To present integrated safety data of belimumab in 3 double-blind studies of systemic lupus erythematosus (SLE), including the full wk-76 data from BLISS-76.

Method: Safety data from 2133 patients with SLE who participated in one phase 2 (LBSL02, N=449) and two phase 3 (BLISS-52, N = 865; BLISS-76, N = 819), multicenter, double-blind, clinical studies of belimumab were evaluated.  Belimumab (1 and 10 mg/kg in all studies; 4 mg/kg in LBSL02 only) or placebo was given by intravenous (IV) infusion on days 0, 14, and 28, and q28d thereafter for 52 weeks in LBSL02, 48 weeks in BLISS-52, and 72 weeks in BLISS-76.  All patients received ≥1 standard therapy (or a combination), eg, corticosteroids, antimalarials, immunosuppressants, and nonsteroidal anti-inflammatory drugs.  Clinical and laboratory assessments were performed during scheduled visits and adverse events (AEs) were evaluated as they occurred. AE rates were based on the double-blind, placebo-controlled phase 2 and phase 3 studies. Malignancy rate was based on exposure to belimumab in all SLE studies (phases 1–3 and open-label continuation; IV and subcutaneous routes).

Result: Rates of AEs overall, by severity and seriousness, and as the cause of discontinuations were similar between placebo and belimumab. Depression was more common with belimumab 1 and 10 mg vs standard therapy alone (6.1% and 5.2% vs 3.7%, respectively). The suicidality rate was the same across treatment groups (0.1%). Infection rates, including lower respiratory infections, as well as infusion/hypersensitivity reactions were numerically higher with belimumab, while all others were comparable with placebo. In all belimumab SLE studies (double-blind and continuation), the rate/100 patient-years (pt-y) of malignancy (excluding nonmelanoma skin cancer) was 0.45, and of mortality was 0.55. No single cause of death predominated; etiologies included infection, cardiovascular disease, and suicide.  

Conclusion: Based on data from 2133 patients (with >4600 pt-y of exposure), belimumab was generally well tolerated when used in combination with a wide range of standard SLE therapy. (ClinicalTrials.gov: NCT00071487/00583362; NCT00424476; NCT00410384.)

 

Integrated Safety Data Through Wk 76a

 

Standard Therapy Plus

 

Placebo

(N = 675)

% Patients

Belimumab 1 mg/kg

(N = 673)

% Patients

Belimumab

10 mg/kg

(N = 674)

% Patients

AE in general

92.7

93.3

93.0

Discontinuation due to AE

7.4

6.4

6.8

Serious/severe AE

22.4

24.1

23.3

Death 

0.4

0.7

0.9

Infection in general

67.4

71.9

70.8

Discontinuation due to infection

1.2

0.7

0.6

Serious/severe infection

6.8

7.6

6.1

Infection of special interest

 

 

 

       Cellulitis

6.7

8.9

6.4

       Sepsis

0.4

0.6

0.7

       Fungal

3.4

3.1

2.5

       Herpes virus

8.0

8.3

6.8

       All respiratory

49.5

52.0

53.0

             Lower respiratory

8.9

11.9

12.3

      Possible opportunisticb

0

0

0.3

Serious/severe infusion/hypersensitivity reactions

0.6

1.2

1.2

Malignant neoplasm

0.3

0.7

0.4

Malignant Neoplasm/Mortality With Belimumab vs Placebo

 

Phase 2/3 Double-blind, Placebo-Controlled

All SLE Studies (Double-blind and Continuation)

Placebo

(N = 675)

(692 pt-y)

Belimumab

(N = 1458)

(1516 pt-y)

Placebo

(N = 688)

(702 pt-y)

Belimumab

(N = 1982)f

(3976 pt-y)

Malignant Neoplasmc,d

Patients with events, n (%)

2 (0.3)

3 (0.2)

2 (0.3)

18 (0.9)

Rate/100 patient-years (95% CI)

0.29

(0.04-1.04)

0.20

(0.04-0.58)

0.28

(0.03-1.03)

0.45

(0.27-0.72)

Mortalitye

Patients with events, n (%)

3 (0.4)

11 (0.75)

3 (0.4)

22 (1.1)

Rate/100 patient-years (95% CI)

0.43

(0.09-1.27)

0.73

(0.36-1.30)

0.43

(0.09-1.25)

0.55

(0.35-0.84)

aPooled data of belimumab 1 and 10 mg/kg compared with placebo; the 4-mg/kg dose (n = 111) was included only in LBSL02, where its safety profile was similar to that of placebo and belimumab 1 and 10 mg/kg in LBSL02; no malignancy, death, or hypersensitivity was reported with the 4-mg/kg dose;  bthere were 2 cases of latent tuberculosis (TB), 1 extrapulmonary TB, 2 Mycobacterium non-TB (1 atypical extrapulmonary and 1 avium complex pulmonary), 1 cytomegalovirus pneumonia, 1 coccidioidomycosis, and 1 Acinetobacter sepsis after day 0; cexcludes non-melanoma skin cancer; dmalignancy rate/100 pt-y of 0.53 (95% CI: 0.48, 0.59) was reported in an international SLE cohort followed for an average of 8 y (76,948 pt-y) (Bernatsky S, Boivin JF, Joseph L, et al. An international cohort study of cancer in systemic lupus erythematosus. Arthritis Rheum. 2005;52:1481-90);  emortality rate/100 pt-y of 1.63 (1.54, 1.72) was reported in an international SLE cohort followed for an average of 8 y (76,948 pt-y) (Bernatsky S, Boivin JF, Joseph L, et al. Mortality in systemic lupus erythematosus. Arthritis Rheum. 2006;54:2550-7); fincludes phases 1‒3 and open-label continuation studies in SLE as of February 2011.

 


Keywords: belimumab and systemic lupus erythematosus (SLE)

Disclosure: D. J. Wallace, Human Genome Sciences, GlaxoSmithKline, 5 ; S. Navarra, Pfizer , 5, Human Genome Sciences, GlaxoSmithKline, Pfizer, MSD, Roche, 8 ; M. Petri, Human Genome Sciences, GlaxoSmithKline, 2, Human Genome Sciences, GlaxoSmithKline, 5 ; A. Gallacher, Human Genome Sciences, Inc., 5 ; R. Gúzman, None; M. Thomas, None; R. A. Furie, Human Genome Sciences, Inc., 2, Human Genome Sciences, GlaxoSmithKline, 5, Human Genome Sciences, GlaxoSmithKline, 8 ; O. Zamani, None; R. A. Levy, Human Genome Sciences/GlaxoSmithKline, 5, Human Genome Sciences/GlaxoSmithKline, 8 ; R. F. van Vollenhoven, Abbott, GlaxoSmithKline, Merck, Roche, Pfizer, UCB Pharma, 2, Abbott, GlaxoSmithKline, Human Genome Sciences, Merck, Roche, Pfizer, UCB Pharma, 5 ; S. Cooper, Human Genome Sciences, Inc., 1, Human Genome Sciences, Inc., 3 ; Z. J. Zhong, Human Genome Sciences, Inc., 1, Human Genome Sciences, Inc., 3 ; W. Freimuth, Human Genome Sciences, Inc., 1, Human Genome Sciences, Inc., 3 ; L. Pineda, Human Genome Sciences, Inc., 1, Human Genome Sciences, Inc., 3 ; R. Cervera, GlaxoSmithKline, Human Genome Sciences, Inc., 5 .