Adventure awaits - before they go, consider cholera protection

Why VAXCHORA?¹

Indication and usage

VAXCHORA is a vaccine indicated for active immunization against disease caused by Vibrio cholerae serogroup O1 in persons 2 through 64 years of age traveling to cholera-affected areas.

Limitations of Use: The effectiveness of VAXCHORA has not been established in persons living in cholera-affected areas. The effectiveness of VAXCHORA has not been established in persons who have pre-existing immunity due to previous exposure to V. cholerae or receipt of a cholera vaccine. VAXCHORA has not been shown to protect against disease caused by V. cholerae serogroup O139 or other non-O1 serogroups.

The Advisory Committee on Immunization Practices (ACIP) recommends VAXCHORA for people 2 through 64 years of age who are traveling to an area with active cholera transmission.^2*

To read the full recommendation and see the most recent updates, visit the CDC website.

*The CDC considers cholera transmission to be active in a country when any of the following criteria are met:

• • WHO reports a cholera outbreak (e.g., annual reports, outbreak bulletins, disease outbreak news)
  • A country reports more than 100 suspected cholera cases in the previous 12 months as documented by reliable, publicly available sources such as WHO or the Ministries of Health
  • CDC experts have reviewed available information and have determined that cholera is likely present even if not officially reported

CDC, Centers for Disease Control and Prevention; WHO, World Health Organization.

Demonstrated Efficacy Profile¹

Efficacy in adults

Study 2 — Challenge Study in Adults Aged 18-45

Study Design: VAXCHORA was studied in a randomized, double-blind, saline placebo–controlled V. cholerae challenge study conducted in U.S. subjects 18 through 45 years of age (N=197) with no prior history of cholera infection or travel to a cholera-endemic area in the previous 5 years were randomized according to a 1:1 ratio to receive 1 dose of VAXCHORA or placebo. The co-primary objectives were to demonstrate the efficacy of a single dose of VAXCHORA in the prevention of moderate to severe diarrhea following challenge at 10 days and 3 months post-vaccination.^1,3,a,b

Pre-specified criteria for success were that the lower bound of the two-sided 95% confidence interval for vaccine efficacy must be ≥30% in both the 10 Day and 3 Month challenge groups.¹

VAXCHORA demonstrated vaccine efficacy against the occurrence of moderate to severe diarrhea following challenge with V. cholerae O1 El Tor Inaba at 10 days and 3 months post-vaccination.

VAXCHORA recipients were divided into 2 cohorts, 1 challenged
at 10 days and the other at 3 months post-vaccination.

Cohort 1

68 healthy volunteers received VAXCHORA (N=35) or placebo (N=33) in the 10-day challenge¹

Efficacy 10 days after vaccination¹

In the 10-day challenge group, 2 volunteers receiving VAXCHORA (2/35, 5.7%) developed moderate to severe diarrhea after challenge with V. cholerae.¹

Cohort 2

66 healthy volunteers received VAXCHORA (N=33) or placebo (N=33) in the 3-month challenge¹

Efficacy 3 months after vaccination¹

In the 3-month challenge group, 4 volunteers taking VAXCHORA (4/33, 12.1%) developed moderate to severe diarrhea after challenge withV. cholerae.¹

In the case of each cohort (10-day and 3-month), evaluation of the relative efficacy of VAXCHORA was made in comparison to the combined outcomes among recipients of placebo in both cohorts.¹

The majority of placebo recipients (39/66, 59.1%) developed moderate or severe diarrhea after being challenged with V. cholerae.¹

• ^a Moderate to severe diarrhea defined as ≥3.0 L or ≥5.0 L, respectively, within 10 days after being challenged with V. cholerae 01 El Tor Inaba.³
• ^b Vaccine efficacy=[(Attack Rate in Placebo Group – Attack Rate in Vaccine Group)/Attack Rate in Placebo Group] x 100.

Immunogenicity (seroconversion) Trials — Studies 1, 4, and 5

A series of immunogenicity trials further contributed to the demonstration of VAXCHORA's efficacy, particularly in other age groups than were enrolled in Study 2. In these studies, immune response to VAXCHORA was based on seroconversion. A vibriocidal antibody assay was used to measure serum levels of neutralizing antibodies against the vaccine strain (classical Inaba), and seroconversion was defined as a ≥4-fold rise in serum vibriocidal antibody from baseline to 10 days post vaccination. Based on an observed association in Study 2 (the challenge study in adults aged 18-45 years) between seroconversion and protection from V. cholerae disease, seroconversion rate at 10 days post-vaccination was used to evaluate response to vaccination in these immunogenicity trials.¹

Study 1 — Immunogenicity Study in Adults Aged 18-45

Study Design: Study 1 was a randomized, double-blind, saline placebo-controlled safety and immunogenicity study conducted in the US and Australia. A total of 3146 subjects 18 through 45 years of age not previously exposed to cholera were randomized 8:1 to receive 1 dose of VAXCHORA or placebo.¹

Seroconversion occurred in 93.5% of vaccine recipients versus 4% of placebo recipients 10 days after vaccination¹

Seroconversion after 10 days

Seroconversion rates (95% CI) were: vaccine recipients, 93.5% (92.5%, 94.4%); placebo, 4% (2%, 7%).¹

Study 4 — Immunogenicity Study in Adults Aged 46-64

Study Design: Study 4 was a randomized, double-blind, placebo-controlled safety and immunogenicity study conducted in the US. A total of 398 subjects 46 through 64 years of age with no prior history of cholera infection or travel to a cholera-endemic area in the previous 5 years were randomized 3:1 to receive 1 dose of VAXCHORA or placebo.¹

Vibriocidal antibody seroconversion rates for the classical Inaba strain were compared at 10 days post-vaccination between subjects 46 through 64 years of age in Study 4 and subjects 18 through 45 years of age in Study 1.

VAXCHORA demonstrated a seroconversion rate of 90.4% in adults 46 through
64 years of age¹

Study 4

Subjects 46 through 64 years of age
(VAXCHORA N=291^a)

Seroconversion rates (95% CI) were: Study 4, 90.4% (86.4%, 93.5%); Study 1 (subjects 18 through 45 years of age; VAXCHORA N=2687), 93.5% (92.5%, 94.4%); difference in seroconversion rates -3.1% (-6.7%, 0.4%).^b

• ^a N represents number of subjects with analyzable samples at Day 1 and Day 11.
• ^b Prespecified success criterion was that the lower bound of the 2-sided 95% CI on the difference in seroconversion rate (Study 4 minus Study 1) must be greater than -10 percentage points.

Efficacy in children and adolescents

Study 5 — Immunogenicity Study in Children and Adolescents Aged 2–17

Study Design: Study 5 was a randomized, double-blind, saline placebo-controlled safety and immunogenicity study conducted in the US. A total of 550 subjects 2 through 17 years of age not previously exposed to cholera were randomized 6:1 to receive one dose of VAXCHORA or placebo. Randomization was stratified by age into 3 cohorts: Cohort 1: 12 to <18 years of age; Cohort 2: 6 to <12 years of age; Cohort 3: 2 to <6 years of age.¹

Classical Inaba vibriocidal antibody seroconversion rates at 10 days post-vaccination were compared with seroconversion rates in adults 18 through 45 years of age in Study 1.

VAXCHORA demonstrated a seroconversion rate of 98.5% in subjects 2 through 17 years of age at 10 days post-vaccination¹

Study 5

Subjects 2 through 17 years of age
(VAXCHORA N=399^a)

Seroconversion rates (98.3% CI) were: Study 5, 98.5% (96.2%, 99.4%); Study 1 (subjects 18 through 45 years of age; VAXCHORA N=2687), 93.5% (92.3%, 94.6%); difference in seroconversion rates 5.0% (2.8%, 6.4%).^b

• ^a N represents number of subjects with analyzable samples at Day 1 and Day 11 in the immunogenicity evaluable population.
• ^b Prespecified success criterion was that the lower bound of the 2-sided 96.7% CI on the difference in seroconversion rate (Study 5 minus Study 1) must be greater than -10 percentage points. Co-primary criterion required the lower limit of the 98.3% CI to be ≥70% for the VAXCHORA group.

Adverse Reactions¹

Adverse reactions in adults

The safety of VAXCHORA was evaluated in more than 3000 volunteers aged 18 to 64 years in 4 randomized, placebo-controlled, multicenter clinical trials.

In a pooled analysis of the 4 clinical studies, 0.6% (20/3235) of VAXCHORA recipients and 0.5% (3/562) of placebo recipients reported a serious adverse event within 6 months post-vaccination. None of these events were considered to be related to vaccination.

Adverse reactions in children and adolescents

The safety of VAXCHORA in children was evaluated in a randomized, placebo-controlled, multicenter clinical trial that included a total of 543 children 2 through 17 years of age. Randomization was stratified by age, and children were enrolled in 3 separate age cohorts: 12-<18 years (Cohort 1), 6 -<12 years (Cohort 2), and 2-<6 years (Cohort 3).

The safety analysis set included 468 VAXCHORA recipients and 75 placebo recipients.

In this trial, 0.2% (1/468) of VAXCHORA recipients and 1.3% (1/75) of placebo recipients reported a serious adverse event within 6 months post-vaccination.

Dosage and Administration¹

VAXCHORA helps deliver cholera protection in just 1 dose

Preparation and administration of VAXCHORA

How Supplied/Storage and Handling¹

How supplied¹

Storage and handling¹

• Store VAXCHORA buffer component and active component packets refrigerated at 36°F to 46°F (2°C to 8°C)
• Protect from light and moisture
• Packages may be stored at 48°F to 77°F (9°C to 25°C) for no more than 24 hours prior to reconstitution
• Dispose of the cup, packets, and stirrer according to standard procedures for medical waste

For medical inquiries about VAXCHORA, please contact Medical Information at
(844) 422-8274 or medical.information_na@bavarian-nordic.com.