The study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not

The study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not reflect the overall results obtained on studies of a product. Before prescribing any product mentioned in this Register, healthcare professionals should consult prescribing information for the product approved in their country. GSK Medicine: Belimumab Study Number: BEL113750 Title: A 52 week study of belimumab versus placebo in the treatment of subjects with systemic lupus erythematosus (SLE) located in Northeast Asia Rationale: The estimated prevalence of SLE in China is considerable and is higher than that in the EU 5 regions (UK, Germany, France, Spain, and Italy).The purpose of this study was to evaluate the efficacy and safety of belimumab administered intravenously (IV) to adult subjects with SLE in Northeast Asia. Phase: III Study Period: 23 May 2011 15 Sep 2015 (Double-blind primary analysis data cut-off date) Study Design: This is a Phase 3, multi-centre, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of belimumab in subjects with active SLE in Northeast Asia. The study consists of a screening period (up to 35 days), a 52-week blinded treatment period, optional open-label treatment, and a follow-up period for subjects not receiving open-label treatment. Subjects who met screening entry criteria were randomized to 1 of 2 treatment groups in a 2:1 ratio: 10 mg/kg belimumab or placebo. Randomization was stratified by screening Safety of Estrogen in Lupus National Assessment (SELENA) SLE Disease Activity Index (SLEDAI) score ( 9 vs. 10), complement levels (low C3 and/or C4 vs. no low C3 or C4), and country of origin (Korea, Japan, China). Subjects who were randomised were to be dosed with investigational product during the blinded treatment period on Days 0, 14, 28 and then every 28 days through Week 48, with a final evaluation at Week 52. Following completion of the blinded treatment period, subjects in China had the option to continue treatment with belimumab in an open-label extension period; the open-label extension period is ongoing. Japan and Korea subjects completing the blinded treatment period may have been eligible to participate in an identical open-label treatment period by enrolling in the BEL114333 continuation study; BEL114333 is ongoing. Subjects not entering the open-label extension period or continuation study were required to return for follow-up visits approximately 8 weeks and 16 weeks after their last dose of investigational product and, in addition, have an assessment of immunogenicity at least 6 months after the last dose of investigational product and/or unblinding of the study (whichever occurred later). Centres: The study was conducted at 49 sites in 3 countries (9 in Korea, 16 in Japan, and 24 in China) Indication: Systemic Lupus Erythematosus Treatment: Investigational product was belimumab 10 mg/kg or placebo control administered by IV infusion on Days 0, 14, 28 and then every 28 days through Week 48. Objectives: The primary objective was to demonstrate the efficacy and safety of belimumab 10 mg/kg compared to placebo, in subjects with SLE in Northeast Asia when added to standard of care therapy at 52 weeks in the blinded period, and the long-term safety and tolerability of belimumab in China subjects with SLE in the open-label period. Primary Outcome (Endpoints)/Efficacy: The primary efficacy endpoint is the SLE responder index (SRI) response rate at Week 52 of the blinded period. SRI response is defined as: 4 point reduction from baseline in SELENA SLEDAI score, AND No worsening (increase of <0.30 points from baseline) in Physician s Global Assessment (PGA), AND No new British Isles Lupus Assessment Group of SLE Clinics (BILAG) A organ domain score or 2 new BILAG B organ domain scores compared with baseline at the time of assessment (i.e., at Week 52 of the blinded period). Secondary Outcome (Endpoints)/Efficacy: Secondary endpoints were: 1. Percent of subjects with 4 point reduction from baseline in SELENA SLEDAI score at Week 52 of the blinded period. 2. Percent of subjects with an SRI7 response defined as a 7 point reduction from baseline in SELENA SLEDAI score, no worsening (increase of <0.30 points from baseline) in PGA, no new BILAG A organ domain score or 2 new BILAG B organ domain scores compared with baseline at the time of assessment (i.e., at Week 52 of the blinded period). 3. Number of days of daily prednisone dose 7.5 mg/day and/or reduced by 50% from baseline over 52 weeks during the blinded period. 4. Time to first severe modified SLE Flare Index (SFI) flare over 52 weeks during the blinded period. Statistical Methods: Double-blind data were locked for the primary analysis (SRI response at Week 52) after data through the Week 52 visit for subjects entering the open-label extension period (i.e., BEL113750 for subjects in China) or continuation study (i.e., BEL114333 for subjects in Japan and Korea) and data through at least 6 months of 1

follow-up (includes 6-month immunogenicity assessment) for subjects not entering the open-label period or the continuation study had been collected, verified and validated. Open-label data will be reported separately. Efficacy analyses were performed on the Modified Intention-To-Treat (MITT) population, defined as all subjects who are randomized and treated with at least one dose of study treatment with the exclusion of subjects from site 086485; as determined prior to unblinding of the double-blind period, 28 subjects from site 086485 were excluded due to issues related to source documentation and disease assessments. Efficacy endpoints were divided into 3 families for hierarchical evaluation based on a pre-specified sequence for the interpretation of statistical significance: 1) Primary efficacy measure (percent of SRI responders at Week 52), 2) Secondary Disease Activity (percent of subjects with 4 point reduction from baseline in SELENA SLEDAI score at Week 52; percent of SRI7 responders at Week 52), and 3) Secondary Disease Management (number of days of daily prednisone dose 7.5 mg/day and/or reduced by 50% from baseline over 52 weeks; time to first severe SFI flare over 52 weeks). To control the type I error rate for multiple comparisons between belimumab vs. placebo for the primary endpoint and subsequent significance tests among the secondary efficacy endpoints, progression through the testing hierarchy of families was dependent upon achieving statistical significance (p 0.05) for each previous family, utilizing the Hochberg procedure to account for the two endpoints in the Secondary Disease Activity and Secondary Disease Management families. Safety analyses were performed on the Safety population, defined as all subjects who are randomized and treated with at least one dose of study treatment. The MITT and Safety analyses were performed according to the treatment that a subject was randomized to receive, regardless of the actual treatment received. Analysis of Primary Efficacy Endpoint: The percentage of subjects achieving an SRI response at Week 52 was presented for belimumab and placebo. A logistic regression model was used to estimate the odds of an SRI response for belimumab vs. placebo. The independent variables in the model included treatment group, country, baseline SELENA SLEDAI score ( 9 vs. 10), and complement levels (low C3 and/or C4 vs. no low C3 or C4). The SRI response at Week 52 data were summarized by the number and percentage of subjects achieving a response by treatment group, the treatment difference versus placebo, the odds ratio and 95% confidence interval (CI) versus placebo and a p-value for the odds ratio. Analysis of Secondary Efficacy Endpoints: The percentage of subjects with a 4 point reduction from baseline in SELENA SLEDAI score at Week 52 was compared between belimumab and placebo using a logistic regression model. The independent variables in the model included treatment group, country, baseline SELENA SLEDAI score ( 9 vs. 10), and complement levels (low C3 and/or C4 vs. no low C3 or C4). The analysis of SRI7 response was conducted for MITT population subjects who had a baseline SELENA SLEDAI score 7. The percentage of subjects achieving an SRI7 response at Week 52 was compared between belimumab and placebo using a logistic regression model. The independent variables in the model included treatment group, country, baseline SELENA SLEDAI score ( 9 vs. 10) and complement levels (low C3and/or C4 vs. no low C3 or C4). The endpoint was summarized by the number and percentage of subjects achieving a response by treatment group, the treatment difference versus placebo, the odds ratio and 95% confidence interval (CI) versus placebo. All analyses of the number of days of daily prednisone dose 7.5 mg/day and/or reduced by 50% from baseline were conducted for subjects in the MITT population who used prednisone >7.5 mg/day at baseline. The number of days of daily prednisone dose 7.5 mg/day and/or reduced by 50% over time through each scheduled visit in the 52-week double-blind phase was compared between belimumab and placebo using a rank analysis of covariance model. The independent variables in the model included treatment group, baseline prednisone dose level, country, baseline SELENA SLEDAI score ( 9 vs. 10), and complement levels (low C3 and/or C4 vs. no low C3 or C4). The endpoint was summarized by the unadjusted mean, median, standard deviation, 25th and 75th percentiles, and minimum and maximum by treatment group. The time to the 1st severe SFI flare over 52 weeks was compared between belimumab and placebo using the Cox proportional hazard model, adjusting for country, baseline SELENA SLEDAI score ( 9 vs. 10), and baseline complement levels (low C3 and/or C4 vs. no low C3 or C4). The endpoint was summarized by the number and percentage of subjects having a severe SFI by treatment group, the hazard ratio and 95% confidence interval (CI) versus placebo. Study Population: Male or female subjects 18 years or older in age with a clinical diagnosis of SLE according to the American College of Rheumatology (ACR) classification criteria, with 4 or more of the 11 ACR criteria being present, and clinically active SLE disease, defined as a SELENA SLEDAI disease activity score of 8 at screening, on a stable SLE treatment regimen for at least 30 days prior to Day 0, and sero-positive for anti-nuclear antibody or anti-dsdna. Subject Disposition Number of Subjects:: Planned, N 234 468 Randomised, N 236 471 Safety Population, N (%) 235 (99.6) 470 (99.8%) MITT Population, N (%) 226 a (95.8) 451 a (95.8%) 2

Completed, n (%) 170 (75.2) 372 (82.5) Total Number Subjects Withdrawn, n (%) 56 (24.8) 79 (17.5) Withdrawn due to Adverse Events, n (%) 22 (9.7) 27 (6.0) Withdrawn due to Lack of Efficacy, n (%) 11 (4.9) 7 (1.6) Withdrawn for other reasons, n (%) 23 (10.2) 45 (10.0) Demographics N (MITT) 226 451 Females: Males 210:16 419:32 Mean Age, years (SD) 31.7 (9.18) 32.3 (9.65) Asian East Asian Heritage, n (%) 195 (86.3) 403 (89.4) a. All 28 subjects randomised at site 086485 are excluded due to issues related to source documentation and disease assessments. Primary Efficacy Results: SRI Response at Week 52 n 217 446 Response, n (%) 87 (40.1) 240 (53.8) Observed difference vs., % 13.72 Odds ratio (95% CI) vs. 1.99 (1.40, 2.82) p-value 0.0001 Secondary Outcome Results: 4 point reduction from baseline in SELENA SLEDAI score at Week 52 n 218 447 Response, n (%) 92 (42.2) 249 (55.7) Observed difference vs., % 13.50 Odds ratio (95% CI) vs. 2.00 (1.41, 2.83) SRI7 response at Week 52 n 183 367 Response, n (%) 43 (23.5) 119 (32.4) Observed difference vs., % 8.93 Odds ratio (95% CI) vs. 1.76 (1.13, 2.74) Days of daily prednisone dose 7.5 mg/day and/or reduced by 50% from baseline over 52 weeks (among subjects with baseline daily prednisone dose >7.5 mg/day) n 184 352 Median (Minimum, Maximum) 0.0 (0, 365) 0.0 (0, 364) 25 th percentile (Q1), 75 th percentile (Q3) 0.0, 172.0 0.0, 213.5 Time to first severe SFI flare over 52 weeks n (%) with severe flare 50 (22.1) 54 (12.0) Hazard ratio (HR) (95% CI) vs. placebo 0.50 (0.34, 0.73) Safety Results: Adverse event (AEs) information was collected from the start of study treatment until the last follow-up contact. Serious AEs (SAEs) were to be collected over the same time period as for AEs. However, SAEs assessed as related to study participation (e.g., investigational product, protocol-mandated procedures, invasive tests, or change in existing therapy) or related to a GSK concomitant medication, were to be recorded from the time a subject consented to participate in the study up to and including any follow up contact. A treatment-emergent AE (i.e., on therapy AE) was defined as an AE that emerged on or after the first treatment dose, having been absent pre-treatment, or that worsened relative to the pre-treatment state. Adverse events that occurred during the 52-week double-blind treatment period are summarized below. (N=235) Most Frequent Adverse Events On-Therapy n (%) n (%) Subjects with any AE(s), n (%) 178 (75.7) 352 (74.9) (N=470) 3

Upper respiratory tract infection 39 (16.6) 65 (13.8) Nasopharyngitis 26 (11.1) 56 (11.9) Pyrexia 21 (8.9) 30 (6.4) Viral upper respiratory tract infection 15 (6.4) 34 (7.2) Cough 16 (6.8) 30 (6.4) Diarrhoea 14 (6.0) 28 (6.0) Herpes zoster 12 (5.1) 29 (6.2) Headache 16 (6.8) 23 (4.9) Urinary tract infection 11 (4.7) 21 (4.5) Upper respiratory tract infection bacterial 13 (5.5) 16 (3.4) Abdominal pain 8 (3.4) 17 (3.6) Urinary tract infection bacterial 2 (0.9) 20 (4.3) Nausea 4 (1.7) 17 (3.6) Hypokalemia 8 (3.4) 11 (2.3) Serious Adverse Events - On-Therapy n (%) [n considered by the investigator to be related to study medication] (N=235) (N=470) Subjects with any SAEs, n (%) [related] 43 (18.3) [9] 58 (12.3) [19] Herpes zoster 2 (0.9) [2] 6 (1.3) [3] Lupus nephritis 5 (2.1) [1] 5 (1.1) [1] Pyrexia 4 (1.7) [1] 2 (0.4) [1] Pneumonia 1 (0.4) [1] 2 (0.4) [1] Abdominal pain 0 2 (0.4) [0] Appendicitis 0 2 (0.4) [0] Hepatic function abnormal 0 2 (0.4) [1] Renal failure 0 2 (0.4) [2] Pyelonephritis acute 0 2 (0.4) [1] Uterine leiomyoma 0 2 (0.4) [0] Lupus encephalitis 1 (0.4) [1] 1 (0.2) [1] Pancytopenia 1 (0.4) [0] 1 (0.2) [0] Skin infection 1 (0.4) [1] 1 (0.2) [0] Acute psychosis 0 1 (0.2) [0] Arthritis salmonella 0 1 (0.2) [0] Bacterial pyelonephritis 0 1 (0.2) [1] Brain stem infarction 0 1 (0.2) [0] Cardiomyopathy 0 1 (0.2) [0] Cataract 0 1 (0.2) [0] Cellulitis 0 1 (0.2) [0] Cerebral infarction 0 1 (0.2) [0] Cervix carcinoma 0 1 (0.2) [0] Contusion 0 1 (0.2) [0] Cytomegalovirus infection 0 1 (0.2) [0] Deep vein thrombosis 0 1 (0.2) [0] Dermatitis allergic 0 1 (0.2) [1] Disseminated tuberculosis 0 1 (0.2) [1] Ectopic pregnancy 0 1 (0.2) [0] Escherichia urinary tract infection 0 1 (0.2) [1] Fractured sacrum 0 1 (0.2) [0] Gastroenteritis 0 1 (0.2) [0] Glaucoma 0 1 (0.2) [0] Haematuria 0 1 (0.2) [1] Haemorrhoidal haemorrhage 0 1 (0.2) [0] Humerus fracture 0 1 (0.2) [0] 4

Hyperkalaemia 0 1 (0.2) [0] Infectious colitis 0 1 (0.2) [1] Jaw fracture 0 1 (0.2) [0] Ligament rupture 0 1 (0.2) [0] Lupus cystitis 0 1 (0.2) [0] Lupus pancreatitis 0 1 (0.2) [0] Lupus pneumonitis 0 1 (0.2) [0] Lupus vasculitis 0 1 (0.2) [1] Meningitis tuberculous 0 1 (0.2) [1] Metrorrhagia 0 1 (0.2) [0] Necrosis ischaemic 0 1 (0.2) [0] Otitis media acute 0 1 (0.2) [0] Pancreatitis chronic 0 1 (0.2) [1] Pneumonia mycoplasmal 0 1 (0.2) [0] Pneumonia streptococcal 0 1 (0.2) [1] Pulmonary hypertension 0 1 (0.2) [0] Retinal detachment 0 1 (0.2) [0] Road traffic accident 0 1 (0.2) [0] Scapula fracture 0 1 (0.2) [0] Sepsis 0 1 (0.2) [1] Suicidal ideation 0 1 (0.2) [0] Synovial cyst 0 1 (0.2) [0] Thyroid adenoma 0 1 (0.2) [0] Tuberculous pleurisy 0 1 (0.2) [1] Viral upper respiratory tract infection 0 1 (0.2) [1] Lung infection 2 (0.9) [0] 0 Proteinuria 2 (0.9) [0] 0 Salmonella sepsis 2 (0.9) [0] 0 SLE arthritis 2 (0.9) [0] 0 Allergic colitis 1 (0.4) [0] 0 Anogenital warts 1 (0.4) [0] 0 Arterial rupture 1 (0.4) [0] 0 Benign breast neoplasm 1 (0.4) [0] 0 Blood creatinine increased 1 (0.4) [0] 0 Cellulitis streptococcal 1 (0.4) [1] 0 Cystitis 1 (0.4) [0] 0 Dysarthria 1 (0.4) [0] 0 Enteritis infectious 1 (0.4) [0] 0 Epilepsy 1 (0.4) [0] 0 Erythema multiforme 1 (0.4) [0] 0 Femoral neck fracture 1 (0.4) [0] 0 Gastrointestinal fungal infection 1 (0.4) [0] 0 Generalised oedema 1 (0.4) [0] 0 Histiocytosis haematophagic 1 (0.4) [0] 0 Hydronephrosis 1 (0.4) [0] 0 Hypoproteinaemia 1 (0.4) [0] 0 Interstitial lung disease 1 (0.4) [0] 0 Intervertebral disc protrusion 1 (0.4) [0] 0 Leukopenia 1 (0.4) [0] 0 Lupus pleurisy 1 (0.4) [0] 0 Lymph node tuberculosis 1 (0.4) [0] 0 Oesophageal varices haemorrhage 1 (0.4) [0] 0 Ovarian adenoma 1 (0.4) [0] 0 Patella fracture 1 (0.4) [0] 0 Phlebitis 1 (0.4) [0] 0 5

Pneumonia bacterial 1 (0.4) [0] 0 Polyserositis 1 (0.4) [0] 0 Respiratory failure 1 (0.4) [0] 0 Spleen tuberculosis 1 (0.4) [1] 0 Suicide attempt 1 (0.4) [0] 0 Systemic lupus erythematosus rash 1 (0.4) [0] 0 Tenosynovitis 1 (0.4) [0] 0 Tuberculosis liver 1 (0.4) [1] 0 Upper respiratory tract infection bacterial 1 (0.4) [0] 0 Ureteric stenosis 1 (0.4) [0] 0 Urinary tract infection enterococcal 1 (0.4) [0] 0 Varicose vein 1 (0.4) [0] 0 Vasculitis 1 (0.4) [0] 0 Subjects with fatal SAEs, n (%) [related] Respiratory Failure 1 (0.4) [0] 0 Conclusion: The SRI response rate at Week 52 was statistically greater in belimumab-treated subjects compared with placebo-treated subjects; the odds of a subject being a SRI responder on belimumab was 1.99 (95% CI: 1.40, 2.82) times the odds of a subject being a SRI responder on placebo (p=0.0001). A greater proportion of subjects in the belimumab group had a 4 point reduction from baseline in SELENA SLEDAI score at Week 52 than subjects in the placebo group, and the SRI7 response rate at Week 52 was greater in belimumab-treated subjects compared with placebo-treated subjects. Among subjects receiving >7.5 mg/day prednisone at baseline, the distributions of the number of days in the 52-week treatment period in which their daily prednisone dose was reduced to 7.5 mg/day and/or by 50% from baseline were similar between treatment groups though more subjects reported a larger number of days (median [Q1, Q3]) in the belimumab group (0 days [0 days, 213.5 days]) than the placebo group (0 days [0 days, 172 days]).. Belimumab-treated subjects had a 50% lower risk of experiencing a severe flare (HR=0.50) relative to placebo-treated subjects. The overall incidence of AEs was similar between treatment groups (placebo, 75.7%; belimumab, 74.9%). The two most common treatment-emergent adverse events in both treatment arms were upper respiratory tract infection and nasopharyngitis. The incidence of all SAEs was proportionally higher with placebo-treated subjects (43 [18.3%]) than with belimumab-treated subjects (58 [12.3%]). The most common treatment-emergent SAEs in placebo-treated subjects were lupus nephritis and pyrexia. The most common treatment-emergent SAEs in belimumab-treated subjects were herpes zoster and lupus nephritis. There was one fatality reported in the placebo group and none in belimumab group. 6