Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1    Pharmacodynamic properties
Pharmacotherapeutic group: Meningococcal vaccines, ATC code: J07AH08.



Menveo_DR V4.0_notification_13.06.2019_clean                              Page 6 of 16 Immunogenicity

The efficacy of Menveo has been inferred by measuring the production of serogroup-specific anti-capsular antibodies with bactericidal activity. Serum bactericidal activity (SBA) was measured using human serum as the source of exogenous complement (hSBA). The hSBA was the original correlate of protection against meningococcal disease.

Immunogenicity was evaluated in randomised, multicenter, active controlled clinical trials that enrolled children (2-10 years of age), adolescents (11-18 years of age), adults (19-55 years of age) and older adults (56-65 years of age).

Immunogenicity in children 2 to 10 years of age

In the pivotal study V59P20 immunogenicity of Menveo was compared to ACWY-D; 1170 children were vaccinated with Menveo and 1161 received the comparator vaccine in the per protocol populations. In two supportive studies V59P8 and V59P10 immunogenicity of Menveo was compared to ACWY-PS.

In the pivotal, randomised, observer-blind study V59P20, in which participants were stratified by age (2 through 5 years and 6 through 10 years), the immunogenicity of a single dose of Menveo one month post vaccination was compared with the single dose of ACWY-D. Immunogenicity results one month after Menveo vaccination among subjects aged 2-5 years and 6-10 years are summarized below in Table 1 
Table 1:      Serum bactericidal antibody responses following Menveo one month after vaccination among subjects aged 2-5 years and 6-10 years

2-5 years                                   6-10 years
Serogroup             hSBA ≥1:8                  hSBA GMTs            hSBA ≥1:8            hSBA GMTs (95% CI)                   (95% CI)             (95% CI)             (95% CI) A                   N=606                      N=606                N=551                N=551 72%                        26                   77%                  35 (68, 75)                   (22, 30)             (74, 81)             (29, 42) C                   N=607                      N=607                N=554                N=554 68%                        18                   77%                  36 (64, 72)                   (15, 20)             (73, 80)             (29, 45) W-135                 N=594                      N=594                N=542                N=542 90%                        43                   91%                  61 (87, 92)                   (38, 50)             (88, 93)             (52, 72) Y                   N=593                      N=593                N=545                N=545 76%                        24                   79%                  34 (72, 79)                   (20, 28)             (76, 83)             (28, 41) 
In another randomised, observer-blind study (V59P8) US children were immunized with a single dose of either Menveo (N=284) or ACWY-PS (N=285). In the children 2-10 years of age, as well as in each age strata (2-5 and 6-10 years), immune response as measured by percentage of subjects with seroresponse, hSBA≥1:8 and GMTs were not only non-inferior to comparator vaccine ACWY-PS, but all were statistically higher than the comparator for all serogroups and all immune measurements at 1 month post vaccination.
At 1 year post vaccination, Menveo continued to be statistically higher than ACWY-PS for serogroups A, W-135 and Y, as measured by percentage of subjects with hSBA≥1:8 and GMTs. Menveo was non-inferior on these endpoints for serogroup C (Table 2). The clinical relevance of higher post-vaccination immune responses is not known.

Table 2:      Immunogenicity of one dose of Menveo or ACWY-PS in subjects 2 through 10 years of age, measured at one month and twelve months post-vaccination

Serogroup                  1 month post-vaccination                         12 months post-vaccination 
Menveo_DR V4.0_notification_13.06.2019_clean                             Page 7 of 16 hSBA ≥1:8                  hSBA GMTs                hSBA ≥1:8               hSBA GMTs (95% CI)                   (95% CI)                 (95% CI)                 (95% CI) Menveo     ACWY-PS          Menveo ACWY-PS          Menveo ACWY-PS           Menveo      ACWY-PS A          N=280        N=281          N=280       N=281       N=253       N=238        N=253        N=238 79%          37%            36          6.31        23%         13%          3.88            3 (74, 84)     (31, 43)       (30, 44) (5.21, 7.64)   (18, 29)     (9, 18)   (3.39, 4.44) (2.61, 3.44) C          N=281        N=283          N=281       N=283       N=252       N=240        N=252        N=240 73%          54%            26           15         53%         44%           11           9.02 (68, 78)     (48, 60)       (21, 34)    (12, 20)    (47, 59)    (38, 51)    (8.64, 13)    (7.23, 11) W-135         N=279        N=282          N=279       N=282       N=249       N=237        N=249        N=237 92%          66%            60           14         90%         45%           42           7.57 (88, 95)     (60, 71)       (50, 71)    (12, 17)    (86, 94)    (38, 51)     (35, 50)    (6.33, 9.07) Y          N=280        N=282          N=280       N=282       N=250       N=239        N=250        N=239 88%          53%            54           11         77%         32%           27           5.29 (83, 91)     (47, 59)       (44, 66)   (9.29, 14)   (71, 82)    (26, 38)     (22, 33)    (4.34, 6.45) 
In a randomised, observer-blind study (V59P10) conducted in Argentina, children were immunized with a single dose of either Menveo (N=949) or ACWY-PS (N=551). Immunogenicity was assessed in a subset of 150 subjects in each vaccine group. The immune response observed in the children 2-10 years of age was very similar to those observed in the V59P8 study shown above: immune response to Menveo at 1 month post vaccination, as measured by percentage of subjects with seroresponse, hSBA≥1:8 and GMTs, was non-inferior to ACWY-PS.

A randomised, observer-blind study was conducted in children 12 to 59 months of age in Finland and Poland (V59P7). A total of 199 subjects 2-5 years of age were in the Menveo per protocol immunogenicity population and 81 subjects 3-5 years of age were in the ACWY-PS group.

At 1 month post-first vaccination, the percentages of subjects with hSBA ≥ 1:8 were consistently higher in the Menveo group for all four serogroups (63% vs 39%, 46% vs 39%, 78% vs 59%, and 65% vs 57% for Menveo as compared to ACWY-PS for serogroups A, C, W-135, and Y, respectively).

In a randomized, observer-blind study (V59_57) conducted in US, immunogenicity of a 2-dose series and a single dose of Menveo was compared in children 2 through 5 and 6 through 10 years of age (N=715).

At baseline, the percentage of subjects with hSBA ≥1:8 across the two age strata was 1%-5% for serogroup A, 13%-28% for serogroup C, 42%-64% for serogroup W-135, and 6%-19% for serogroup Y. At 1 month post last vaccination, the percentages of subjects with hSBA ≥1:8 in the 2-dose group and in the single dose group across the two age strata were: 90%-95% vs 76%–80% for serogroup A, 98%-99% vs 76%-87% for serogroup C, 99% vs 93%-96% for serogroup W-135, and 96% vs 65%-69% for serogroup Y. GMTs were higher in the 2-dose group than the single dose group at 1 month after vaccination in both age strata; however, this difference was less pronounced in the older age stratum.
At 1 year post last vaccination, the percentages of subjects with hSBA ≥1:8 after the 2-dose series and the single dose were both lower than at 1 month post-vaccination (30% after the 2-dose series, 11%-20% after the single dose for serogroup A; 61%-81% and 41%-55% for serogroup C; 92%-94% and 90%-91% for serogroup W-135; 67%-75% and 57%-65% for serogroup Y). The differences between hSBA GMTs in the 2-dose and the single dose groups at 1 year after vaccination were lower than those seen at 1 month post-vaccination.
The clinical benefit of a 2-dose vaccination series in children 2 through 10 years of age is not known.

Persistence of immune response and booster response in children 2 to 10 years of age 
Antibody persistence at 5 years after primary vaccination was assessed in study V59P20E1, this was an extension of study V59P20. There was antibody persistence observed against serogroups C, W-135 and Y, with the percentages of subjects with hSBA ≥ 1:8 being 32% and 56% against serogroup C in subjects 2-5 and 6-10 years of age, respectively, 74% and 80% against serogroup W-135, and 48% and 53% against serogroup Y. GMTs were respectively 6.5 and 12 for serogroup C, 19 and 26 for serogroup W-135, and 8.13 and 10 for serogroup Y. For serogroup A, 14% and 22% of subjects 2-5 and 6-10 years of age, respectively, had hSBA ≥ 1:8 (GMTs 2.95 and 3.73).
Menveo_DR V4.0_notification_13.06.2019_clean                              Page 8 of 16 The children also received a booster dose of Menveo, 5 years after a single dose primary vaccination. All subjects in both age groups had hSBA ≥ 1:8 across all serogroups, with antibody titers several fold higher than seen after the primary vaccination (Table 3).

Table 3: Persistence of immune responses 5 years after primary vaccination with Menveo, and immune responses 1 month after a booster dose among subjects aged 2 - 5 years and 6 -10 years at the time of primary vaccination

Serogroup                          2-5 years                                             6-10 years 5 year persistence      1 month after booster          5 year persistence      1 month after booster hSBA          hSBA                      hSBA                           hSBA          hSBA      hSBA GMTs hSBA ≥1:8                 hSBA ≥1:8
≥1:8         GMTs                      GMTs                           GMTs           ≥1:8      (95% CI) (95% CI)                  (95% CI)
(95% CI)      (95% CI)                  (95% CI)                       (95% CI)      (95% CI) 
A           N=96         N=96             N=95      N=95          N=64             N=64         N=60          N=60 2.95
14%                         100%         361           22%              3.73         100%         350 (2.42,
(7, 22)                    (96, 100)   (299, 436)     (13, 34)       (2.74, 5.06)   (94, 100)   (265, 463) 3.61)
C           N=96         N=96           N=94        N=94          N=64             N=64          N=60         N=60 32%           6.5          100%         498           56%               12          100%          712 (23, 43)    (4.75, 8.9)    (96, 100)   (406, 610)     (43, 69)        (7.72, 19)    (94, 100)   (490, 1036) W-135          N=96         N=96           N=95        N=95          N=64             N=64          N=60         N=60 1534                                                     1556
74%           19           100%                       80%              26           100% (1255,                                                   (1083,
(64, 82)     (14, 25)      (96, 100)                  (68, 89)         (18, 38)     (94, 100) 1873)                                                     2237)
Y           N=96         N=96             N=94      N=94           N=64            N=64         N=59          N=59 1693                                                     1442
48%          8.13          100%                       53%               10          100%
(1360,                                                   (1050,
(38, 58)    (6.11, 11)     (96, 100)                  (40, 66)        (6.51, 16)    (94, 100) 2107)                                                     1979)


Immunogenicity in individuals 11 years of age and above

In the pivotal study (V59P13), adolescents or adults received either a dose of Menveo (N = 2649) comparator vaccine ACWY-D (N = 875). Sera were obtained both before vaccination and 1 month after vaccination.

In another study (V59P6) conducted in 524 adolescents, the immunogenicity of Menveo was compared to that of ACWY-PS.

Immunogenicity in adolescents

In the 11-18 year old population of the pivotal study, V59P13, the immunogenicity of a single dose of Menveo one month post vaccination is compared with the ACWY-D. Immunogenicity results at one month after Menveo are summarized below in Table 4.

Table 4:      Serum bactericidal antibody responses following Menveo one month after vaccination among subjects aged 11-18 years

GMT                            hSBA ≥ 1:8
Serogroup                         N
(95% CI)                          (95% CI)
A                              1075                     29 (24, 35)                      75% (73, 78) C                              1396                     50 (39, 65)                      85% (83, 87) W-135                           1024                    87 (74, 102)                      96% (95, 97) Y                              1036                     51 (42, 61)                      88% (85, 90) 
In the subset of subjects aged 11-18 years who were seronegative at baseline (hSBA < 1:4), the proportion of subjects who achieved a hSBA ≥ 1:8 after a dose of Menveo were as follows: serogroup A 75% (780/1039); serogroup C 80% (735/923); serogroup W-135 94% (570/609); serogroup Y 81% (510/630).
Menveo_DR V4.0_notification_13.06.2019_clean                                     Page 9 of 16 In the non-inferiority study, V59P6, immunogenicity was assessed among adolescents aged 11-17 years who had been randomised to receive either Menveo or ACWY-PS. Menveo was shown to be non-inferior to ACWY-PS vaccine for all four serogroups (A, C, W-135 and Y) based on seroresponse, proportions achieving hSBA ≥1:8, and GMTs.

Table 5:        Immunogenicity of one dose of Menveo or ACWY-PS in adolescents, measured at one month post vaccination
 hSBA ≥1:8                                   hSBA GMTs
Serogroup                             (95% CI)                                    (95% CI) Menveo                 ACWY-PS             Menveo                ACWY-PS A                    N=140                   N=149               N=140                  N=149 81%                     41%                 33                     7.31 (74, 87)                (33, 49)            (25, 44)             (5.64, 9.47) C                    N=140                   N=147               N=140                  N=147 84%                     61%                 59                      28 (77, 90)                (53, 69)            (39, 89)               (19, 41) W-135                   N=138                   N=141               N=138                  N=141 91%                     84%                 48                      28 (84, 95)                (77, 89)            (37, 62)               (22, 36) Y                    N=139                   N=147               N=139                  N=147 95%                     82%                 92                      35 (90, 98)                (75, 88)           (68, 124)               (27, 47) 
At one year post vaccination in these same subjects, compared with ACWY-PS, a higher proportion of subjects vaccinated with Menveo had hSBA ≥1:8 for serogroups C, W-135, and Y, with comparable levels for serogroup A. Similar findings were observed in the comparison of hSBA GMTs.

Persistence of immune response and booster response in adolescents
In study V59P13E1, the persistence of immune responses against serogroups A, C, W-135 and Y was assessed at 21 months, 3 years and 5 years post primary vaccination among subjects aged 11-18 years at the time of vaccination. The percentages of subjects with hSBA ≥ 1:8 remained constant against serogroups C, W-135, and Y from 21 months to 5 years postvaccination in the Menveo group and decreased slightly over time against serogroup A (Table 6). At 5 years after primary vaccination, there were significantly higher percentages of subjects with hSBA ≥ 1:8 in the Menveo group than in the vaccine-naive control subjects against all the four serogroups.

Table 6:        Persistence of immune responses approximately 21 months, 3 years and 5 years after vaccination with Menveo (subjects were aged 11-18 years at the time of vaccination) 
Percentages of subjects with hSBA≥1:8         hSBA GMTs
Serogroup                Timepoint
Menveo                            Menveo
N=100                           N=100
45                         6.57 (4.77-9.05)
21 months
(35, 55)
A                                                    38                         5.63 (3.97-7.99) 3 years
(28, 48)
35                         4.43 (3.13-6.26)
5 years
(26, 45)
N=100                           N=100
61                           11 (8.12-15)
21 months
(51, 71)
C
68                            16 (11-25)
3 years
(58, 77)
5 years                        64                           14 (8.83-24) Menveo_DR V4.0_notification_13.06.2019_clean                           Page 10 of 16 Percentages of subjects with hSBA≥1:8          hSBA GMTs
Serogroup                Timepoint
Menveo                            Menveo
(54, 73)
N=99                             N=99
86                            18 (14-25)
21 months
(77, 92)
W-135                                                  85                            31 (21-46) 3 years
(76, 91)
85                            32 (21-47)
5 years
(76, 91)
N=100                           N=100
71                            14 (10-19)
21 months
(61, 80)
Y                                                     69                            14 (9.68-20) 3 years
(59, 78)
67                            13 (8.8-20)
5 years
(57, 76)

A booster dose of Menveo was administered 3 years after primary vaccination with Menveo or ACWY-D.
Both groups showed a robust response to the booster dose of Menveo at one month after vaccination (100% of subjects had hSBA ≥ 1:8 across serogroups) and this response largely persisted through 2 years after the booster dose for serogroups C, W-135 and Y (with 87% to 100% of subjects with hSBA ≥ 1:8 across serogroups). A small decline was observed in percentages of subjects with hSBA ≥ 1:8 against serogroup A, although percentages were still high (77% to 79%). GMTs declined over time as expected but remained between 2- and 8-fold higher than prebooster values (Table 8).

In study V59P6E1, at one year post vaccination, the percentage of Menveo recipients with hSBA ≥ 1:8 remained significantly higher compared with ACWY-PS recipients for serogroups C, W-135 and Y, and similar between the two study groups for serogroup A. hSBA GMTs for serogroups W-135 and Y were higher among Menveo recipients. In 5 years post vaccination, the percentage of Menveo recipients with hSBA ≥ 1:8 remained significantly higher compared with ACWY-PS recipients for serogroups C and Y. Higher hSBA GMTs were observed for serogroups W-135 and Y (Table 7).

Table 7:       Persistence of immune responses approximately 12 months and 5 years after vaccination with Menveo and ACWY-PS (subjects were aged 11-18 years at the time of vaccination) 
Percentages of subjects with hSBA GMTs hSBA≥1:8
Serogroup        Timepoint                                 P Value                                    P Value Menveo ACWY-PS Menveo vs               Menveo        ACWY-PS        Menveo vs ACWY-PS                                     ACWY-PS
N=50        N=50                       N=50            N=50
41%         43%                        5.19            6.19
12 months                                  0.73                                        0.54 A                           (27, 56)    (28, 59)                 (3.34, 8.09)    (3.96, 9.66) 30%         44%                        5.38            7.75
5 years                                   0.15                                        0.24 (18, 45)    (30, 59)                 (3.29, 8.78)     (4.83, 12)
N=50        N=50                       N=50            N=50
82%         52%                         29              17
12 months                                 <0.001                                       0.22 C                           (68, 91)    (37, 68)                   (15, 57)       (8.55, 33) 76%         62%                         21              20
5 years                                   0.042                                       0.92 (62, 87)    (47, 75)                   (12, 37)        (12, 35)
N=50        N=50                       N=50            N=50
92%         52%                         41              10
12 months                                 <0.001                                     <0.001 W-135                          (80, 98)    (37, 68)                   (26, 64)       (6.41, 16) 72%         56%                         30              13
5 years                                   0.093                                      0.012 (58, 84)    (41, 70)                   (18, 52)       (7.65, 22)

Menveo_DR V4.0_notification_13.06.2019_clean                           Page 11 of 16 Percentages of subjects with hSBA GMTs hSBA≥1:8
Serogroup        Timepoint                                 P Value                                           P Value Menveo ACWY-PS Menveo vs                   Menveo          ACWY-PS         Menveo vs ACWY-PS                                            ACWY-PS
N=50        N=50                           N=50              N=50
78%         50%                            34                9.28
12 months                                   0.001                                             <0.001 Y                           (63, 88)    (35, 65)                       (20, 57)          (5.5, 16) 76%         50%                            30                8.25
5 years                                   0.002                                             <0.001 (62, 87)    (36, 64)                       (18, 49)         (5.03, 14) 
A booster dose of Menveo was administered 5 years after primary vaccination with Menveo or ACWY-PS.
At 7 days after the booster dose, 98%-100% of subjects who previously received Menveo and 73%-84% of subjects who previously received ACWY-PS achieved hSBA ≥1:8 against serogroups A, C, W-135 and Y. At one month post vaccination, the percentages of subjects with hSBA≥1:8 were 98%-100% and 84%-96%, respectively.

A significant increase in the hSBA GMTs against all four serogroups was also observed at 7 and 28 days after the booster dose (Table 8).

Table 8:      Response to Booster: bactericidal antibody responses to Menveo booster administered at 3 or 5 years after the primary vaccination with Menveo or ACWY-PS in subjects aged 11-17 years

Percentages of subjects with hSBA≥1:8                       hSBA GMTs V59P13E1               V59P6E1            V59P13E1                    V59P6E1 Serogroup      Time point      (3 years post         (5 years post       (3 years post              (5 years post vaccination)          vaccination)        vaccination)               vaccination) Menveo       Menveo       ACWY-PS         Menveo            Menveo         ACWY-PS N=42          N=49          N=49          N=42              N=49             N=49 21%           29%           43%           2.69              5.16             7.31 Pre-booster
(10, 37)      (17, 43)      (29, 58)    (1.68, 4.31)       (3.46, 7.7)      (4.94, 11) 100%           73%                             1059              45
7 days             -                                         -
A                                         (93, 100)      (59, 85)                      (585, 1917)        (25, 80) 100%           98%           94%          326                819              147                  28 days
(92, 100)     (89, 100)      (83, 99)    (215, 494)        (514, 1305)       (94, 232) 79%                                       22
2 years                           -             -                                -              -
(63, 90)                                 (12, 41)
N=42          N=49          N=49         N=42               N=49            N=49 55%           78%           61%           16                 20             19 Pre-booster
(39, 70)      (63, 88)      (46, 75)    (8.66, 31)          (13, 33)        (12, 31) 100%           78%                             1603            36
7 days             -                                         -
C                                         (93, 100)      (63, 88)                      (893, 2877)       (20, 64) 100%          100%           84%           597               1217            51                  28 days
(92, 100)     (93, 100)      (70, 93)   (352, 1014)        (717, 2066)       (30, 86) 95%                                       124
2 years                           -             -                                -              -
(84-99)                                  (62-250)
N=41          N=49          N=49          N=41              N=49            N=49 88%           73%           55%            37                29              12 Pre-booster
(74, 96)      (59, 85)      (40, 69)     (21, 65)           (17, 49)       (7.02, 19) 100%           84%                             1685             34
7 days             -                                         -
W-135                                        (93, 100)      (70, 93)                      (1042, 2725)      (21, 54) 100%          100%           92%         673                 1644             47                  28 days
(91, 100)     (93, 100)      (80, 98)   (398, 1137)        (1090, 2481)      (32, 71) 100%                                      93
2 years                           -             -                                -
(91, 100)                                (58, 148)


Menveo_DR V4.0_notification_13.06.2019_clean                               Page 12 of 16 Percentages of subjects with hSBA≥1:8                         hSBA GMTs V59P13E1               V59P6E1              V59P13E1                   V59P6E1 Serogroup       Time point     (3 years post         (5 years post         (3 years post             (5 years post vaccination)          vaccination)          vaccination)              vaccination) Menveo       Menveo       ACWY-PS           Menveo            Menveo        ACWY-PS N=42          N=49          N=49            N=42              N=49            N=49 74%           78%           51%              14                28              7.8 Pre-booster
(58, 86)      (63, 88)      (36, 66)       (8.15, 26)         (18, 45)       (4.91, 12) 98%           76%                               2561             21
7 days             -                                           -
Y                                         (89, 100)      (61, 87)                        (1526, 4298)      (13, 35) 100%          100%           96%            532                2092             63                  28 days
(92, 100)     (93, 100)     (86, 100)      (300, 942)        (1340, 3268)      (41, 98) 95%                                         55
2 years                          -             -                                 -               -
(84, 99)                                   (30, 101)

Immunogenicity in adults

In the pivotal immunogenicity trial, V59P13, immune responses to Menveo were assessed among adults aged 19 to 55 years. Results are presented in Table 9. In the subset of subjects aged 19-55 years who were seronegative at baseline, the proportion of subjects who achieved a hSBA ≥ 1:8 after a dose of Menveo were as follows: serogroup A 67% (582/875); serogroup C 71% (401/563); serogroup W-135 82% (131/160); serogroup Y 66% (173/263).

Table 9:      Serum bactericidal antibody responses following Menveo one month after vaccination among subjects aged 19-55 years

GMT                                 hSBA ≥ 1:8
Serogroup                      N
(95% CI)                               (95% CI)
A                        963                      31 (27, 36)                           69% (66, 72) C                        902                      50 (43, 59)                           80% (77, 83) W135                      484                     111 (93, 132)                          94% (91, 96) Y                        503                      44 (37, 52)                           79% (76, 83) 
The onset of immune response after the primary vaccination with Menveo in healthy subjects 18 through 22 years of age was evaluated in study V59P6E1. At 7 days post vaccination, 64% of subjects achieved hSBA ≥1:8 against serogroup A and 88% through 90% of subjects had bactericidal antibodies against serogroups C, W-135 and Y. At one month post vaccination, 92% through 98% of subjects had hSBA ≥1:8 against serogroups A, C, W-135 and Y. A robust immune response as measured by hSBA GMTs against all serogroups was also observed at 7 days (GMTs 34 through 70) and 28 days (GMTs 79 through 127) after a single dose vaccination.

Immunogenicity in older adults

The comparative immunogenicity of Menveo vs. ACWY-PS was evaluated in subjects aged 56-65 years, in study V59P17. The proportion of subjects with hSBA ≥ 1:8 was non-inferior to ACWY-PS for all four serogroups and statistically superior for serogroups A and Y (Table 10).

Table 10:     Immunogenicity of one dose of Menveo or ACWY-PS in adults aged 56-65 years, measured at one month post vaccination.

Menveo                                      ACWY-PS
Serogroup                             hSBA ≥ 1:8                                    hSBA ≥ 1:8 (95% CI)                                      (95% CI)
N=83                                          N=41
A                                     87%                                           63% (78, 93)                                      (47, 78)
C                                    N=84                                          N=41 Menveo_DR V4.0_notification_13.06.2019_clean                                 Page 13 of 16 90%                                    83%
(82, 96)                               (68, 93)
N=82                                   N=39
W-135                                   94%                                    95% (86, 98)                               (83, 99)
N=84                                   N=41
Y                                    88%                                    68% (79, 94)                               (52, 82)

Available data in children 2 to 23 months of age

The immunogenicity of Menveo in children 2 to 23 months of age was evaluated in several studies. Although a high percentage of subjects achieved hSBA titres above 1:8 following 4-dose series of Menveo, with lower percentages in studies of 2-dose series and of a single dose, Menveo was compared to another meningococcal vaccine in only one pivotal study, where it failed to show a response at least equivalent to a monovalent conjugated serotype C vaccine (after a single dose at the age of 12 months). Currently available data are not sufficient to establish the efficacy of Menveo in children under 2 years of age. See section 4.2 for information on paediatric use.

Pharmacokinetic Properties

5.2    Pharmacokinetic properties

Not applicable.