Vaxchora in Children and Adolescents

James McCarty, MD

Clinical Professor of Pediatrics, Stanford University

Consultant, Emergent BioSolutions

25 February 2021
Agenda

2 ACIP CHOLERA PRESENTATION

• Overview of Vaxchora clinical program

• PXVX-VC-200-006 study 

• Acceptability / Palatability

• Safety 

• Immunogenicity

• Summary
Vaxchora Clinical Development Program

3

Study Age Range Dose # Subjects† (Active) Objectives Results

Phase 1

0021 18 to 50 4.34 x 108 CFU 66 (55)

Safety

Immunogenicity

Kinetics (shedding)

Well-tolerated

SVA 88.9% (D14)

Stool+ 11% (throughD7)

Challenge 

Phase 3

0032

18 to 45 5 x 108 CFU 197 (95)

Efficacy (challenge)

Immunogenicity

SVA 79.8% (D8)

SVA 89.4% (D11)

Efficacy 90.3% (D11)

Efficacy 79.5% (D91)

Lot Consistency 

Phase 3

0043

18 to 45 1 x 109 CFU 3146 (2795)

Lot consistency

Safety

Immunogenicity

Met consistency criteria

Well-tolerated

SVA: 93.5% (D11)

Older Adult 

Phase 3

0054

46 to 64 1 x 109 CFU 398 (299)

Safety

Immunogenicity

Bridging

Well-tolerated

SVA 90.4%(D11)

Non-inferior to 004

Pediatric

Phase 4

0065,6

2 to 17 1 x 109 CFU 550 (468)

Safety

Immunogenicity

Bridging

Well-tolerated

SVA 98.5%(D11)

Non-inferior to 004

†Placebo in the phase 1 trial was lactose powder in water. Placebo was physiological saline in all other trials. 

CFU=colony-forming unit; SVA=serum vibriocidal antibody.

1. Chen WH, et al. Clin Vaccine Immunol. 2014;21(1):66-73. 2. Chen WH, et al. Clin Infect Dis. 2016;62(11):1329-1335. 3. McCarty JM, et al. Vaccine. 2018;36:833-840. 4. McCarty JM, et al. Vaccine. 2019;37:1389-1397. 5. McCarty 

JM, et al. Am J Trop Med Hyg. 2020;102(1):48-57. 6. McCarty JM, et al. Am J Trop Med Hyg. 2020, online ahead of print.

ACIP CHOLERA PRESENTATION
The Efficacy of Vaxchora Was Assessed in a

Placebo-Controlled Challenge Study (003)1

4

1. Chen WH, et al. Clin Infect Dis. 2016;62(11):1329-1335. 2. Haney DJ, et al. Clin Vaccine Immunol. 2017;24:e00098-e117. 

Vaxchora

(N=95)

Saline Placebo

(N=102)

Healthy Adults

(18–45 years) randomized 1:1, double-blinded

Day 11 

Challenge

(N=35)

Day 91 

Challenge

(N=33)

Day 11 

Challenge

(N=33)

Day 91 

Challenge

(N=33)

No 

Challenge

(N=27)

No 

Challenge

(N=36)

• Protective efficacy against moderate (≥3.0 - 5 L) to severe (≥5.0 L) cholera diarrhea was 90.3% at Day 11 

and 79.5% at Day 911

• Vibriocidal antibody seroconversion was determined to be an immune correlate of protection2

ACIP CHOLERA PRESENTATION
Vaxchora 006 Pediatric Study Design1,2

SVA=serum vibriocidal antibody 

1. McCarty JM, et al. Am J Trop Med Hyg. 2020;102(1):48-57. 2. McCarty JM, et al. Am J Trop Med Hyg. 2020; online ahead of print.

5

6 to 11

Years

N=185 Placebo 

N=27

Vaxchora 

N=158

12 to 17

Years

N=189 Placebo 

N=26

Vaxchora 

N=163

2 to 5

Years

N=245 Placebo 

N=35

Vaxchora 

N=210

Main Study

Vaxchora 

Vaxchora 

Vaxchora 

Vaxchora 

Placebo Crossover

Long-Term Immunogenicity (Sub-study)

Analysis Endpoints:

• Immunogenicity (SVA)

• Seroconversion rate at Day 11

• Cumulative seroconversion at Day 29

• Geometric mean titer (GMT)

• 12 to 17 years: through Day 730

• 2 to 11 years: through Day 29

• Safety

• Solicited adverse events through Day 8

• Unsolicited adverse events (including 

serious adverse events)

• Dosing and Palatability

• Percent of dose consumed

• Reported palatability (subjective)

ACIP CHOLERA PRESENTATION
Screened

Randomized

Dosed

Evaluable at Day 11

Completed Day 181

Completed Day 730

(12 to 17 sub study only)

Vaxchora 006 Pediatric Study

Enrollment and Disposition1,2

1. McCarty JM, et al. Am J Trop Med Hyg. 2020;102(1):48-57. 2. McCarty JM, et al. Am J Trop Med Hyg. 2020; online ahead of print.

6 ACIP CHOLERA PRESENTATION
Vaxchora 006 Pediatric Study

Demographics

7 ACIP CHOLERA PRESENTATION

• Mean age: 9.0 years

• 51.6% male

• Racial demographics

• 59.5% - White

• 31.3% - Black

• 7.7% - Multiracial

• 0.9% - Asian

• 0.6% - American Indian / Alaskan Native

• Ethnic demographics

• 8.7% Hispanic or Latinx

1. Data on file, Emergent BioSolutions Inc, Bedell L, 2020.
Vaxchora 006 Pediatric Study 

Dosing and Palatability1,2

*The unblinded dose administrator had the option to add PureVia Stevia sweetener to the oral solution at the request of the parent and/or participant.

†Percentage of subjects who received any amount of dose (Dose Given).

1. Bennett SR, CISTM, 2019. 2. McCarty JM, et al. Am J Trop Med Hyg. 2020;102(1):48-57. 

8

Age Group 2 to 5 6 to 11 12 to 17

Vaxchora

N=150

Placebo

N=26

Vaxchora

N=158

Placebo

N=27

Vaxchora

N=163

Placebo

N=26

Dose volume, mL 50 50 100 100 100 100

Dose given 146 (97.3%) 26 (100%) 156 (98.7%) 26 (96.3%) 163 (100%) 26 (100%)

Sweetener added*† 144 (98.6%) 26 (100%) 149 (95.5%) 25 (96.2%) 144 (88.3%) 22 (84.6%)

Complete dose consumed† 116 (79.5%) 19 (73.1%) 142 (91.0%) 25 (96.2%) 162 (99.4%) 26 (100%)

≥80% of dose consumed† 121 (82.9%) 22 (84.6%) 152 (97.4%) 25 (96.2%) 162 (99.4%) 26 (100%)

Palatability†:

Very good 44 (30.1%) 6 (23%) 28 (17.9%) 3 (11.5%) 8 (4.9%) 2 (7.7%)

Good 28 (19.2%) 9 (35%) 27 (17.3%) 1 (3.8%) 29 (17.8%) 6 (23.1%)

Neutral 19 (13.0%) 3 (12%) 37 (23.7%) 10 (38.5%) 64 (39.3%) 10 (38.5%)

Bad 24 (16.4%) 4 (15%) 30 (19.2%) 6 (23.1%) 50 (30.7%) 7 (26.9%)

Very bad 31 (21.2%) 4 (15%) 34 (21.8%) 6 (23.1%) 12 (7.4%) 1 (3.8%)

ACIP CHOLERA PRESENTATION
Safety Overview of Vaxchora (004 & 006)1 Percent of Subjects

0

10

20

30

40

50

60

70

2- to 5-year olds

(N=148)

6- to 11-years olds

(N=162)

12- to 17-year olds† 

(N=166)

Adults*

(N=2789)

Solicited AEs

Related

Solicited AEs

Unsolicited AEs

Related

Unsolicited AEs

Serious AEs

(N=150) (N=158) (N=163)

*In the adult population all solicited AEs were presumed to be related.

†There were no related serious AEs; 1 unrelated serious AEs of right leg fracture was noted.

AE=adverse events.

1. Bennett SR, CISTM, 2019.

9 ACIP CHOLERA PRESENTATION

 
Solicited AEs by Specific Event and Frequency (006)1,2

*AE=adverse event.

1. McCarty JM, et al. Am J Trop Med Hyg. 2020;102(1):48-57. 2. McCarty JM, et al. Am J Trop Med Hyg. 2020; online ahead of print.

10

Abdominal pain and lack of appetite were frequent in the vaccine group in the 12- to 17-year cohort but were not significantly 

higher compared to placebo. Vomiting, diarrhea, and fever were relatively infrequent in all age groups.

0

10

20

30

40

50

Vaxchora Placebo

12- to 17-Years Cohort

Percent of subjects reporting AEs

0

10

20

30

40

50

Vaxchora

6- to 11-Years Cohort

Placebo

Percent of subjects reporting AEs

Vaxchora

2- to 5-Years Cohort

0

10

20

30

40

50

Percent of subjects reporting AEs

Placebo

ACIP CHOLERA PRESENTATION
Serious Adverse Events (SAEs) (006)1,2

11

•

•

SAEs were reported in 0.2% (1/468) of Vaxchora recipients and 1.3% (1/75) 

of placebo recipients within 6 months post-vaccination 

None of these events were considered related to vaccination

1. McCarty JM, et al. Am J Trop Med Hyg. 2020;102(1):48-57. 2. McCarty JM, et al. Am J Trop Med Hyg. 2020; online ahead of print..

ACIP CHOLERA PRESENTATION
Primary Endpoint: SVA Seroconversion at Day 11 (006) 

(Adult vs Pediatric; Vaxchora Only)1,2,3

SVA=serum vibriocidal antibody.

1. McCarty JM, et al. Am J Trop Med Hyg. 2020;102(1):48-57. 2. McCarty JM, et al. Am J Trop Med Hyg. 2020; online ahead of print. 3. McCarty JM, et al. Vaccine. 2018;36:833-840. 

12

Age Group 2 to 5 6 to 11 12 to 17 Adults 

18 to 45

N, evaluable 103 139 157 2687

N, seroconverted 101 136 156 2513

Percent seroconversion 

(98.3% CI)

98.1 

(91.5–99.6)

97.8 

(92.5–99.4)

99.4 

(95.4–99.9)

93.5 

(92.3–94.6)

Difference:

(pediatrics minus adults)

(96.7% CI)

+4.6 

(-1.0 to +6.4)

+4.3 

(-0.3 to +6.2)

+5.8

(+2.4 to +7.1) N/A

P-value 

(Fisher’s Exact test) 0.0628 0.0455 0.0009 N/A

Primary objectives met for each age cohort.

Noninferiority with adults (lower bound of 96.7% CI for difference >-10%).

Minimum seroconversion (lower bound of 98.3% CI >70%).

Adult reference population from study 200-0043

ACIP CHOLERA PRESENTATION
SVA Seroconversion at Day 11 (006)1,2 

98.1 97.8 99.4 93.5

0

20

40

60

80

100

 2- to 5-year-olds 6- to 11-year-olds 12- to 17-year-olds 18-to 45-year-olds

Vaxchora seroconversion, %

Noninferiority criteria for seroconversion were met for each age cohort 

and seroconversion rates were similar to adults*

*95% CI for ages 2–5 years=91.5%–99.6%, 6–11 years=93.8%–99.3%, 12–17 years=96.5%–99.9%, 18–45 years=92.3%–94.6%.

SVA=serum vibriocidal antibody.

1. McCarty JM, et al. Am J Trop Med Hyg. 2020;102(1):48-57. 2. McCarty JM, et al. Am J Trop Med Hyg. 2020; online ahead of print.

13 ACIP CHOLERA PRESENTATION
Cumulative SVA Seroconversion at Day 29 (006)

(Pediatric Only; Vaxchora vs Placebo)1,2

98.1

0

97.8

8.3

100

0

0

10

20

30

40

50

60

70

80

90

100

2 to 5:

Vaxchora

(N=103)

2 to 5:

Placebo

(N=20)

6 to 11:

Vaxchora

(N=139)

6 to 11:

Placebo

(N=24)

12 to 17:

Vaxchora

(N=157)

12 to 17:

Placebo

(N=23)

Percent of subjects, %

*Vaxchora 95% CI for ages 2–5 years=91%–98.8%, 6–11 years=93.8%–99.3%, 12–17 years=97.6%–100%. Placebo 95% CI for ages 2–5 years=94.4%–99.7%1 

SVA=serum vibriocidal antibody.

1. McCarty JM, et al. Am J Trop Med Hyg. 2020;102(1):48-57. 2. McCarty JM, et al. Am J Trop Med Hyg. 2020; online ahead of print.

14 ACIP CHOLERA PRESENTATION
Log 10 Titer SVA GMT

Study Day

1 11 29 91 181

GMTs of Serum Vibriocidal Antibody Through Day 181 (006)1,2

Children and Adults

1

2

3

4

SVA=serum vibriocidal antibody; GMT=geometric mean titer.

1. McCarty JM, et al. Am J Trop Med Hyg. 2020;102(1):48-57. 2. McCarty JM, et al. Am J Trop Med Hyg. 2020; online ahead of print.

15

In the 2-5 years and 6-11 years age groups, titers were followed to day 29 only. 

In the 12- to 17-years age group, SVA GMTs in Vaxchora recipients remained significantly higher than placebo at day 181.

ACIP CHOLERA PRESENTATION
Vaxchora Long Term Immunogenicity Subset (006)1

Adolescents 12-17 years of age

16

Time Point SVA Seroconversion Rate GMT GMFI

Vaxchora

(n=72)

Placebo

(n=23)

Vaxchora 

(n=72)

Placebo

(n=23)

Vaxchora 

(n=72)

Placebo

(n=23)

Day 11 100% 0 9035.4 41.2 279.2 0.9

Day 29 100% 0 2791.7 42.5 86.3 1.0

Day 91 88.9% 0 391.7 42.5 12.1 1.0

Day 181 83.1% 0 223.0 38.7 6.9 0.9

Day 365 68.6% N/A 158.4 N/A 4.8 N/A

Day 547 73.1% N/A 175.6 N/A 5.2 N/A

Day 730 64.5% N/A 133.8 N/A 4.1 N/A

SVA=serum vibriocidal antibody; GMT=geometric mean titer; GMFI=geometric mean fold increase.

N/A: Seroconversion was measured in placebo subjects through Day 181.

1. McCarty JM, et al. ASTMH Annual Meeting, 2020.

ACIP CHOLERA PRESENTATION
Partial Dosing: SVA Seroconversion at Day 11 (006)

Stratified by Portion of Dose Consumed1*

*Among Vaxchora subjects (modified intent-to-treat population) who consumed less than 80% of expected dose. 

SVA=serum vibriocidal antibody.

1. Data on file, Emergent BioSolutions.

17

Age Group < 50% of Dose 50 to < 80% of Dose Total 

(< 80% of Dose)

2 to 5 years 11/16 (68.8%) 6/6 (100%) 17/22 (77.3%)

6 to 11 years 6/9 (66.7%) 1/1 (100%) 7/10 (70.0%)

12 to 17 years 1/1 (100%) 0/0 1/1 (100%)

All age 

groups 18/26 (69.2%) 7/7 (100%) 25/33 (75.8%)

ACIP CHOLERA PRESENTATION
Summary

18

•

•

•

•

Vibriocidal antibody seroconversion rates in children and adolescents 2 to 17 

years of age immunized with Vaxchora were non-inferior to seroconversion rates 

in adults

Vaxchora was well-tolerated in the pediatric population, with no vaccinerelated serious adverse events

In an immunogenicity subset of Vaxchora recipients 12-17 years of age, serum

vibriocidal antibody GMTs remained elevated 2 years post-vaccination

Vibriocidal antibody seroconversion occurred in most children who received 

only partial doses of the vaccine

ACIP CHOLERA PRESENTATION
Conclusion

19

•

•

Vaxchora is a single-dose vaccine with demonstrated safety and efficacy 

Vaxchora may be used for the prevention of cholera in travelers 2-17 years of 

age visiting high risk areas

ACIP CHOLERA PRESENTATION
Discussion
Backup
22

The Efficacy of Vaxchora Was Assessed in a

Placebo-Controlled Challenge Study (003)1

Results

1. Chen WH, et al. Clin Infect Dis. 2016;62(11):1329-1335.

Placebo

All Challenge

Vaxchora

D11 Challenge

Vaxchora

D91 Challenge

N 66 35 33

Mild diarrhea (< 3L), n (%) 22 (33.3) 3 (8.6) 11 (33.3)

Moderate (3-5 L), n (%) 11 (16.7) 1 (2.9) 2 (6.1)

Severe (>5L), n (%) 28 (42.4) 1 (2.9) 2 (6.1)

Moderate or severe, n (%) 39 (59.1) 2 (5.7) 4 (12.1)

Protective efficacy (%) n/a 90.3 79.5

ACIP CHOLERA PRESENTATION
In the Human Challenge Study (003), Vibriocidal Antibody 

Seroconversion Was Determined to Be an Immune Correlate of 

Protection1,2

Fold increase in vibriocidal titer 

(baseline to 10 days post-vaccination)

Cumulative diarrhea (L)

P

P

P

PP

P

P

P

P

P

P

P

P

P

P

P

P

P

P

P

P

P

P

P

P

P

P

P

P

P

P

P

P

P

P

P

P

P

P

P

P

P

P

P

P

P

P

P

P

P

P

P

P

P

P

P

P

P

P

V

1 4 16 64 256 1024

0

1

16

4

2

8

Placebo Subjects (n = 66)

Vaccinees (n = 68)

Severe Cholera

Moderate Cholera

r=0.71, P<0.01

P V V V

V

V

V

V

V

V

V

V

V

V

V V

V

V

V V

V

V V

V

VV VV V V

V

V VV V

V

V

V

V

V

V V

V

V

V

V

V V V V V V

V

V

V

V

V

V

V

V VV V

V

V V

V

V

23

1. Chen WH, et al. Clin Infect Dis. 2016;62(11):1329-1335. 2. PaxVax, Inc. Data on file.

ACIP CHOLERA PRESENTATION
Vaxchora with Sweetener or Flavoring Added: 

Potency Testing

24

•

•

•

•

•

Internal testing evaluated the potency of Vaxchora over a 30-minute period after 

sweetener was stirred in to 50 mL reconstituted vaccine

The amount of CFU remained within the pre-specified range (4 x 108 to 2 x 109) 

of live attenuated Vibrio cholerae CVD 103-HgR with the addition of:

1 gram of PureVia®, Truvia®, Splenda® Naturals, SweetLeaf®, or Sweet 

Additions® brand stevia

OR

Up to 4 grams of sucrose (table sugar)

FLAVORx® children’s medicine flavoring was not compatible with the vaccine, likely 

because it contains propylene glycol, which is bactericidal to some organisms

ACIP CHOLERA PRESENTATION

CFU = colony forming units

1. Data on file, Emergent BioSolutions Inc, Duffin P, 2020.

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