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

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1 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:GlaxoSmithKline (GSK) Biologicals Fluarix /Influsplit SSW 2013/2014 vaccine Study Number: (FLUARIX-072) Title: A Phase III study for evaluation of immunogenicity and reactogenicity of Fluarix/Influsplit SSW 2013/2014 in people 18 years of age and above. Fluarix (Flu): GlaxoSmithKline (GSK) Biologicals trivalent inactivated split virion influenza vaccine. Rationale: The purpose of this study was to test the immunogenicity and safety of the Flu vaccine containing the influenza strains recommended for the season. Phase: III Study Period: 12-July-2013 to 02-August-2013 Study Design: Open-label, non-randomised, multi-centre study with 2 parallel age groups (18-60 years and >60 years). Centres: 4 centres in Germany. Indication: Immunization of adults against influenza Treatment: The study groups were as follows: Adult Group: Subjects aged years received 1 dose of Flu vaccine at Day 0. Elderly Group: Subjects aged >60 years received 1 dose of Flu vaccine at Day 0. The study vaccine was administered intramuscularly in the deltoid region of the non-dominant arm. Objectives: To evaluate the humoral response [anti-haemagglutinin (HA) antibodies tested by Haemagglutination Inhibition (HI)] against each vaccine strain in adults years and >60 years of age, 21 days after vaccination with Flu vaccine. Primary Outcome/Efficacy Variable: Immunogenicity Observed variable: Humoral immune response in terms of anti-ha antibodies against each of the 3 vaccine influenza strains. Derived variables: The following parameters were calculated with 95% confidence intervals (CIs): At Days 0 and 21 Geometric mean titres (GMTs) of anti-ha antibody titres. Seroprotection rates* (SPR). At Day 21 Seroconversion rates** (SCR). Mean geometric increase*** ([MGI] also known as the seroconversion factor [SCF]). Seroprotection power**** (SPP). *SPR was defined as the percentage of vaccinees with serum HI titre 1:40. **SCR was defined as the percentage of vaccines with either a pre-vaccination titre < 1:10 and a post-vaccination tire 1:40 or a pre-vaccination titre 1:10 and at least 4-fold increase in post-vaccination titre. ***MGI/SCF was defined as the fold increase in serum HI geometric mean titres post-vaccination compared to Day 0. ****SPP was defined as the percentage of subjects who had a pre-vaccination titre < 1:40 and a post-vaccination titre 1:40. Secondary Outcome/Efficacy Variable(s): Safety Occurrence of solicited local and general symptoms Percentage, intensity and duration of solicited local symptoms during a 4-day follow-up period after vaccination (i.e. day of vaccination and 3 subsequent days). Percentage, intensity, duration and relationship to vaccination of solicited general symptoms during a 4-day follow-up period after vaccination (i.e. day of vaccination and 3 subsequent days). Occurrence of unsolicited symptoms Percentage, intensity and relationship to vaccination of unsolicited symptoms during a 21-day follow-up period after vaccination (i.e. day of vaccination and 20 subsequent days). Occurrence of serious adverse events (SAEs) Percentage, intensity and relationship to vaccination of SAEs during the entire study period.

2 Immunogenicity Observed variable: Humoral immune response in terms of anti-ha antibodies against each of the 3 vaccine influenza strains, in subjects aged years and >60 years who had and who had not received an influenza vaccine during the 2 influenza seasons prior to season 2012/2013. Derived variables: The following parameters were calculated with s: At Days 0 and 21 GMTs of anti-ha antibody titres and SPRs, in subjects who had and who had not received an influenza vaccine during the 2 influenza seasons prior to season 2012/2013. At Day 21 SCRs and MGI in subjects who had and who had not received an influenza vaccine during the 2 influenza seasons prior to season 2012/2013. Statistical Methods: The analyses were performed on the Total Vaccinated cohort and the According-to-Protocol (ATP) cohort for immunogenicity. The Total Vaccinated cohort included all vaccinated subjects for whom data were available. The ATP cohort for immunogenicity included all evaluable subjects (i.e., those meeting all eligibility criteria, complying with the procedures and intervals defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity outcome variables were available. This included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination. Analysis of Immunogenicity The analysis was performed on the ATP cohort for immunogenicity. For the humoral immune response in terms of anti-ha antibodies against each of the 3 vaccine influenza strains, the following parameters (with s) were calculated for each group: Seropositivity rates and GMTs of anti-ha antibody titres at Days 0 and 21. SCRs, MGI and SPP at Day 21. SPRs at Days 0 and 21. For the humoral immune response in terms of anti-ha antibodies against each of the 3 vaccine influenza strains in subjects who had and who had not received an influenza vaccine during the 2 influenza seasons prior to season 2012/2013, the following parameters were calculated with s for each treatment group: Seropositivity rates and GMTs of anti-ha antibody titres at Days 0 and 21. SPR at Days 0 and 21. SCRs and MGI at Day 21. Analysis of Safety: The analysis was performed on the Total Vaccinated cohort. For each solicited local and general symptom, the percentages of subjects with the symptom reported within 4-day (Days 0-3) following the vaccination were tabulated with exact for each group. The same tabulation was performed for grade 3 symptoms, as well as for solicited general symptoms assessed by the investigator as causally related to vaccination. The durations of these solicited local and general symptoms during the 4-day (Days 0-3) post-vaccination period were also tabulated. The percentage of subjects with at least one unsolicited adverse events (AEs) within the 21 days (Days 0-20) following the vaccination was tabulated for each group according to the Medical Dictionary for Regulatory Activities (MedDRA) preferred terms. The same tabulation was performed for grade 3 unsolicited AEs and for unsolicited AEs assessed by the investigator as related to vaccination. The percentage of subjects reporting SAEs and that of SAEs assessed by the investigators as related to the vaccination were tabulated according to the MedDRA preferred terms for each group during the entire study period. Study Population: Healthy or with well-controlled chronic diseases male or female subjects aged 18 years or above at the time of the vaccination who did not participate in the previous year s Flu registration study (116663). Females of childbearing potential had to practice adequate contraception for 30 days prior to vaccination, had a negative pregnancy test the day of vaccination and had agreed to continue such precautions for 2 months after vaccination. A written informed

3 consent was obtained from the subjects prior to study entry. Number of Subjects: Adult Group Elderly Group Planned, N Enrolled, N (Total Vaccinated cohort) Completed, n (%) 60 (100) 60 (100) Total Number Subjects Withdrawn, n (%) 0 (0.0) 0 (0.0) Withdrawn due to Adverse Events, n (%) 0 (0.0) 0 (0.0) Withdrawn due to Lack of Efficacy, n (%) Not Applicable Not Applicable Withdrawn for other reasons, n (%) 0 (0.0) 0 (0.0) Demographics Adult Group Elderly Group N (Total Vaccinated cohort) Sex, n (%) Females 38 (63.3) 34 (56.7) Males 22 (36.7) 26 (43.3) Mean Age, years (SD) 42.6 (11.50) 68.2 (5.49) Median Minimum, Maximum 20, 61 61,83 White - Caucasian / European heritage, n (%) 60 (100) 60 (100) Primary Efficacy Results: Seropositivity rates and GMTs for HI antibody titre at Day 0 and Day 21 (ATP cohort for immunogenicity) 1:10 GMT Antibody Group Timing N n % LL UL Value LL UL Flu A/Christchurch/16/2010 (H1N1) Adult PRE PI(D21) Elderly PRE PI(D21) Flu A/Texas/50/2012 (H3N2) Adult PRE PI(D21) Elderly PRE PI(D21) Flu B/Massachusetts/2/2012 (Yamagata) Adult PRE PI(D21) Elderly PRE PI(D21) GMT = geometric mean antibody titre calculated on all subjects N = number of subjects with available results n/% = number/percentage of subjects with titre within the specified range = 95% confidence interval; LL = Lower Limit, UL = Upper Limit PRE = Pre-vaccination at Day 0 PI(D21) = Post-vaccination at Day 21 Primary Efficacy Results: SPR for HI antibody titre at Day 0 and Day 21 (ATP cohort for immunogenicity) SPR Antibody Group Timing N n % LL UL Flu A/Christchurch/16/2010 (H1N1) Adult PRE PI(D21) Elderly PRE PI(D21) Flu A/Texas/50/2012 (H3N2) Adult PRE PI(D21) Elderly PRE PI(D21) Flu B/Massachusetts/2/2012 (Yamagata) Adult PRE PI(D21) Elderly PRE

4 PI(D21) SPR = Seroprotection rate N = Number of subjects with available results n/% = number/percentage of seroprotected subjects (HI titre 1:40) PRE = Pre-vaccination at Day 0 PI(D21) = Post-vaccination at Day 21 Primary Efficacy Results: SCR for HI antibody titre at Day 21 (ATP cohort for immunogenicity) SCR Antibody Group N n % LL UL Flu A/Christchurch/16/2010 (H1N1) Adult Elderly Flu A/Texas/50/2012 (H3N2) Adult Elderly Flu B/Massachusetts/2/2012 (Yamagata) Adult Elderly Seroconversion defined as: For initially seronegative subjects, antibody titre 1:40 after vaccination For initially seropositive subjects, antibody titre after vaccination 4 fold the pre-vaccination antibody titre N = Number of subjects with pre- and post-vaccination results available n/% = number/percentage of seroconverted subjects Primary Efficacy Results: MGI for HI antibody titre at Day 21 (ATP cohort for immunogenicity) MGI Antibody Group N Value LL UL Flu A/Christchurch/16/2010 (H1N1) Adult Elderly Flu A/Texas/50/2012 (H3N2) Adult Elderly Flu B/Massachusetts/2/2012 (Yamagata) Adult Elderly N = Number of subjects with pre- and post-vaccination results available MGI = Geometric mean of the within -subject ratios of the post-vaccination reciprocal HI titre to the Day 0 reciprocal HI titre Primary Efficacy Results: SPP for HI antibody titre at Day 21 (ATP cohort for immunogenicity) SPP Antibody Group N n % LL UL Flu A/Christchurch/16/2010 (H1N1) Adult Elderly Flu A/Texas/50/2012 (H3N2) Adult Elderly Flu B/Massachusetts/2/2012 (Yamagata) Adult Elderly SPP = Seroprotection Powers N = number of subjects unprotected at pre-vaccination and with available results n/% = number/percentage of subjects unprotected at pre-vaccination and protected at Day 21 Secondary Outcome Results: Seropositivity rates and GMTs for HI antibody titre at Day 0 and Day 21 by influenza vaccination status in subjects who had and who had not received an influenza vaccine during the 2 influenza seasons prior to season 2012/2013 (ATP cohort for immunogenicity) 1:10 GMT Antibody Group Sub-group Timing N n % LL UL Value LL UL

5 Flu A/Christchurch/16/2010 (H1N1) Adult Yes PRE PI(D21) No PRE PI(D21) Elderly Yes PRE PI(D21) No PRE PI(D21) Flu A/Texas/50/2012 (H3N2) Adult Yes PRE PI(D21) No PRE PI(D21) Elderly Yes PRE PI(D21) No PRE PI(D21) Flu B/Massachusetts/2/2012 Adult Yes PRE (Yamagata) PI(D21) No PRE PI(D21) Elderly Yes PRE PI(D21) No PRE PI(D21) Yes = Subjects received an influenza vaccine during the 2 influenza seasonal prior to season No = Subjects did not receive an influenza vaccine during the 2 influenza seasonal prior to season GMT = geometric mean antibody titre calculated on all subjects N = number of subjects with available results n/% = number/percentage of subjects with titre within the specified range = 95% confidence interval; LL = Lower Limit, UL = Upper Limit PRE = Pre-vaccination at Day 0 PI(D21)= Post-vaccination at Day 21 Secondary Outcome Results: SPR for HI antibody titre at Day 0 and Day 21 by influenza vaccination status in subjects who had and who had not received an influenza vaccine during the 2 influenza seasons prior to season 2012/2013 (ATP cohort for immunogenicity) SPR Antibody Group Sub-group Timing N n % LL UL Flu A/Christchurch/16/2010 (H1N1) Adult Yes PRE PI(D21) No PRE PI(D21) Elderly Yes PRE PI(D21) No PRE PI(D21) Flu A/Texas/50/2012 (H3N2) Adult Yes PRE PI(D21) No PRE PI(D21) Elderly Yes PRE PI(D21) No PRE PI(D21) Flu B/Massachusetts/2/2012 (Yamagata) Adult Yes PRE PI(D21)

6 No PRE PI(D21) Elderly Yes PRE PI(D21) No PRE PI(D21) Yes = Subjects received an influenza vaccine during the 2 influenza seasonal prior to season No = Subjects did not receive an influenza vaccine during the 2 influenza seasonal prior to season N = Number of subjects with available results n/% = number/percentage of seroprotected subjects (HI titre 1:40) PRE = Pre-vaccination at Day 0 PI(D21)= Post-vaccination at Day 21 Secondary Outcome Results: SCR for HI antibody titre at Day 21 by influenza vaccination status in subjects who had and who had not received an influenza vaccine during the 2 influenza seasons prior to season 2012/2013 (ATP cohort for immunogenicity) SCR Antibody Group Sub-group N n % LL UL Flu A/Christchurch/16/2010 (H1N1) Adult Yes No Elderly Yes No Flu A/Texas/50/2012 (H3N2) Adult Yes No Elderly Yes No Flu B/Massachusetts/2/2012 (Yamagata) Adult Yes No Elderly Yes No Yes = Subjects received an influenza vaccine during the 2 influenza seasonal prior to season No = Subjects did not receive an influenza vaccine during the 2 influenza seasonal prior to season Seroconversion defined as: For initially seronegative subjects, antibody titre 1:40 after vaccination For initially seropositive subjects, antibody titre after vaccination 4 fold the pre-vaccination antibody titre N = Number of subjects with pre- and post-vaccination results available n/% = number/percentage of seroconverted subjects Secondary Outcome Results: MGI for HI antibody titre at Day 21 by influenza vaccination status in subjects who had and who had not received an influenza vaccine during the 2 influenza seasons prior to season 2012/2013 MGI Antibody Group Sub-group N Value LL UL Flu A/Christchurch/16/2010 (H1N1) Adult Yes No Elderly Yes No Flu A/Texas/50/2012 (H3N2) Adult Yes No Elderly Yes No Flu B/Massachusetts/2/2012 (Yamagata) Adult Yes No Elderly Yes No

7 Yes = Subjects received an influenza vaccine during the 2 influenza seasonal prior to season No = Subjects did not receive an influenza vaccine during the 2 influenza seasonal prior to season N = Number of subjects with pre- and post-vaccination results available MGI = Geometric mean of the within -subject ratios of the post-vaccination reciprocal HI titre to the Day 0 reciprocal HI titre Secondary Outcome Results: Number (%) of subjects reporting solicited local symptoms during the 4-day (Days 0-3) post-vaccination period (Total Vaccinated cohort) Adult Group Elderly Group 95 % CI 95 % CI Symptom Intensity N n % LL UL N n % LL UL Ecchymosis Any >100mm Induration Any >100mm Pain Any Redness Any >100mm Swelling Any >100mm N = number of subjects with the documented dose n/% = number/percentage of subjects reporting at least once the symptom = Exact 95% confidence interval; LL = lower limit; UL = upper limit Any = occurrence of any specified solicited symptoms regardless of intensity grade Grade 3 pain = Significant pain at rest which prevented normal every day activities. Secondary Outcome Results: Number of days of solicited local symptoms during the 4-day post-vaccination period (Total Vaccinated cohort) Symptom Group N Mean Median Induration Elderly Pain Adult Elderly Redness Adult Elderly Swelling Adult Elderly N = Number of subjects with the symptom and without the missing confirmed grade Secondary Outcome Results: Number (%) of subjects reporting solicited general symptoms during the 4-day (Days 0-3) post-vaccination period (Total Vaccinated cohort) Adult Group Elderly Group 95 % CI 95 % CI Symptom Intensity/Relationship N n % LL UL N n % LL UL Arthralgia Any Related Fatigue Any Related Gastrointestinal symptoms Any Related Headache Any Grade Related Myalgia Any Related

8 Shivering Any Related Sweating Any Related Temperature/(Axillary) 37.5 C >39.0 C Related N= number of subjects with the documented dose n/%= number/percentage of subjects reporting the symptom at least once when the intensity is maximum Any = occurrence of any specified solicited symptoms regardless of intensity grade or relationship to vaccination Grade 3 symptom = Symptom that prevented normal activities Related = Symptom assessed by the investigator as causally related to the vaccination. = Exact 95% confidence interval; LL = lower limit, UL = upper limit Secondary Outcome Results: Number of days of solicited general symptoms during the 4-day post-vaccination period (Total Vaccinated cohort) Symptom Group N Mean Median Arthralgia Adult Elderly Fatigue Adult Elderly Gastrointestinal symptoms Adult Elderly Headache Adult Elderly Myalgia Adult Elderly Sweating Adult Elderly Shivering Adult Temperature Elderly N = Number of subjects with the symptom and without the missing confirmed grade Safety Results: Number (%) of subjects reporting the occurrence of unsolicited AEs, within the 21-day (Days 0-20) postvaccination period (Total Vaccinated cohort) Most Frequent Adverse Events On-Therapy (occurring within Days 0-20 following vaccination) Adult Group N=60 Elderly Group N=60 Subjects with any AE(s), n (%) 5 (8.3) 3 (5.0) Subjects with Grade 3 AEs, n (%) 0 (0.0) 0 (0.0) Subjects with Related AEs, n (%) 0 (0.0) 1 (1.7) Vertigo - 1 (1.7) Toothache 1 (1.7) - Nasopharyngitis 1 (1.7) - Rhinitis - 1 (1.7) Arthropod bite 1 (1.7) 1 (1.7) Headache 1 (1.7) - Dysphonia - 1 (1.7) Dyspnoea 1 (1.7) 1 (1.7) Epistaxis - 1 (1.7) -: AE absent Grade 3 = AE that prevented normal activity Related = AE assessed by the investigator as causally related to the study vaccination Safety Results: Number (%) of subjects reporting SAEs, during the entire study period (Days 0-180) (Total Vaccinated cohort) Serious adverse event, n (%) [n considered by the investigator to be related to study medication] All SAEs Adult Group Elderly Group

9 N=60 N=60 Subjects with any SAE(s), n (%)[n assessed by investigator as related] 0 (0.0) [0] 0 (0.0) [0] Fatal SAEs Adult Group N=60 Elderly Group N=60 Subjects with fatal SAE(s), n (%)[n assessed by investigator as related] 0 (0.0) [0] 0 (0.0) [0] Conclusion: At Day 0, GMTs for HI antibodies against the H1N1, H3N2 and Yamagata strains were 27.3, 15.8 and 105.0, respectively in the Adult Group. At that same time point, in the Elderly Group, GMTs for HI antibodies against the H1N1, H3N2 and Yamagata strains were 15.7, 14.2 and 95.2, respectively. At Day 21, GMTs for HI antibodies against the H1N1, H3N2 and Yamagata strains were 444.6, 73.8 and 424.6, respectively in the Adult Group. At that same time point, in the Elderly Group, GMTs for antibodies against the H1N1, H3N2 and Yamagata strains were 197.0, 80.0 and 327.5, respectively. At Day 0, 41.7%, 20.0% and 88.3% of subjects in the Adult Group and 23.3%, 20.0% and 91.7% of subjects in the Elderly Group were seroprotected against the H1N1, H3N2 and Yamagata strains, respectively. At Day 21, 96.7%, 83.3% and 100% of subjects in the Adult Group and 93.3%, 73.3% and 100% of subjects in the Elderly Group were seroprotected against the H1N1, H3N2 and Yamagata strains, respectively. At Day 21, 73.3%, 51.7% and 50.0% of subjects in the Adult Group and 76.7%, 48.3% and 38.3% of subjects in the Elderly Group were seroconverted against the H1N1, H3N2 and Yamagata strains, respectively. At Day 21, MGI for antibody titre against the H1N1, H3N2 and Yamagata strains was 16.3, 4.7 and 4.0, respectively in the Adult Group and 12.6, 5.6 and 3.4 against the H1N1, H3N2 and Yamagata strains, respectively in the Elderly Group. At Day 21, in the Adult Group the seroprotection power was, 94.3%, 79.2% and 100% against the H1N1, H3N2 and Yamagata strains, respectively. At the same time point, in the Elderly Group seroprotection power was, 91.3%, 66.7% and 100% against the H1N1, H3N2 and Yamagata strains, respectively. Within the 21-day post vaccination period, 5 subjects (8.3%) in Adult Group and 3 subjects (5.0%) in Elderly Group reported at least one unsolicited AE. There were no SAEs reported during the entire study period (Day 0 to Day 21). Date Updated: 23-October-2014