First Cholera Vaccine Approved.

June 10, 2016

The U.S. Food and Drug Administration approved Vaxchora, a vaccine for the prevention of cholera caused by serogroup O1 in adults 18 through 64 years of age traveling to cholera-affected areas.

Vaxchora is the only FDA-approved vaccine for the prevention of cholera.

Cholera, a disease caused by Vibrio cholerae bacteria, is acquired by ingesting contaminated water or food and causes a watery diarrhea that can range from mild to extremely severe. Often the infection is mild; however, severe cholera is characterized by profuse diarrhea and vomiting, leading to dehydration. It is potentially life threatening if treatment with antibiotics and fluid replacement is not initiated promptly. According to the World Health Organization, serogroup O1 is the predominant cause of cholera globally.

DESCRIPTION

Vaxchora is a live, weakened vaccine that is taken as a single, oral liquid dose of approximately three fluid ounces at least 10 days before travel to a cholera-affected area.

VAXCHORA (Cholera Vaccine, Live, Oral) is a live, attenuated bacterial vaccine suspension for oral administration containing the V. cholerae strain CVD 103-HgR. CVD 103-HgR was constructed from the serogroup O1 classical Inaba strain 569B by deleting the catalytic domain sequence of both copies of the ctxA gene, which prevents the synthesis of active cholera toxin (CT).

This attenuated strain remains able to synthesize the immunogenic non-toxic B subunit of CT (encoded by the ctxB gene). In addition, a marker was inserted into the hemolysin gene locus (hlyA) to enable differentiation of the vaccine strain from wild type V. cholerae O1.

The vaccine strain is grown in fermentors under controlled conditions in medium containing casamino acids, yeast extract, mineral salts, and an anti-foaming agent.

The bacteria are collected by filtration, diafiltered, and concentrated before addition of a stabilization solution containing ascorbic acid (an antioxidant), Hy-Case SF (hydrolyzed casein [a protein derived from cow’s milk], a cryoprotectant), sodium chloride (a stabilizer), and sucrose (a cryoprotectant). The stabilized bacteria are lyophilized, milled, and blended with dried lactose (a desiccant and bulking agent). The active component blend is filled into packets.

After reconstitution, VAXCHORA contains 4 x 108 to 2 x 109 colony forming units (CFU) of live attenuated V. cholerae CVD 103-HgR. The resulting suspension should be slightly cloudy and may contain white particulates.

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CLINICAL PHARMACOLOGY

Mechanism of Action

VAXCHORA contains live attenuated cholera bacteria that replicate in the gastrointestinal tract of the recipient. Immune mechanisms conferring protection against cholera following receipt of VAXCHORA have not been determined. However, rises in serum vibriocidal antibody 10 days after vaccination with VAXCHORA were associated with protection in a human challenge study.

INDICATIONS AND USAGE

VAXCHORA is a vaccine indicated for active immunization against disease caused by Vibrio cholerae serogroup O1. VAXCHORA is approved for use in adults 18 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.

DOSAGE AND ADMINISTRATION

  • For oral administration only.
  • Administer a single oral dose of VAXCHORA a minimum of 10 days before potential exposure to cholera.
  • The safety and effectiveness of revaccination with VAXCHORA have not been established.
  • Instruct recipients to avoid eating or drinking for 60 minutes before or after oral ingestion of VAXCHORA.

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SAFETY & EFFICACY

Vaxchora’s efficacy was demonstrated in a randomized, placebo-controlled human challenge study of 197 U.S. volunteers from 18 through 45 years of age. Of the 197 volunteers, 68 Vaxchora recipients and 66 placebo recipients were challenged by oral ingestion of Vibrio cholerae, the bacterium that causes cholera. Vaxchora efficacy was 90 percent among those challenged 10 days after vaccination and 80 percent among those challenged three months after vaccination.  The study included provisions for administration of antibiotics and fluid replacement in symptomatic participants. To prevent transmission of cholera into the community, the study included provisions for administration of antibiotics to participants not developing symptoms.

Two placebo-controlled studies to assess the immune system’s response to the vaccine were also conducted in the U.S. and Australia in adults 18 through 64 years of age. In the 18 through 45 year age group, 93 percent of Vaxchora recipients produced antibodies indicative of protection against cholera. In the 46 through 64 years age group, 90 percent produced antibodies indicative of protection against cholera. The effectiveness of Vaxchora has not been established in persons living in cholera-affected areas.

The safety of Vaxchora was evaluated in adults 18 through 64 years of age in four randomized, placebo-controlled, multicenter clinical trials; 3,235 study participants received Vaxchora and 562 received a placebo.

CONTRAINDICATIONS

Do not use in persons who have a history of severe allergic reaction (e.g., anaphylaxis) to any ingredient of VAXCHORA or to a previous dose of any cholera vaccine

WARNINGS AND PRECAUTIONS

  • The safety and effectiveness of VAXCHORA have not been established in immunocompromised persons.
  • VAXCHORA may be shed in the stool of recipients for at least 7 days.
  • There is a potential for transmission of the vaccine strain to nonvaccinated close contacts (e.g., household contacts). Use caution when considering whether to administer VAXCHORA to individuals with immunocompromised close contacts.

ADVERSE REACTIONS

The most common adverse reactions (incidence > 3%) were tiredness (30%), headache (28%), abdominal pain (18%), nausea/vomiting (17%), lack of appetite (16%) and diarrhea (4%).

DRUG INTERACTIONS

  • Avoid concomitant administration of VAXCHORA with systemic antibiotics since these agents may be active against the vaccine strain.
  • Do not administer VAXCHORA to patients who have received oral or parenteral antibiotics within 14 days prior to vaccination.
  • Immune responses to VAXCHORA may be diminished when VAXCHORA is administered concomitantly with chloroquine. Administer VAXCHORA at least 10 days before beginning antimalarial prophylaxis with chloroquine.

The FDA granted the Vaxchora application fast track designation andpriority review status.

In addition, the FDA awarded the manufacturer of Vaxchora a tropical disease priority review voucher, under a provision included in the Food and Drug Administration Amendments Act of 2007. This provision aims to encourage the development of new drugs and biological products for the prevention and treatment of certain tropical diseases.

Vaxchora is manufactured by PaxVax Bermuda Ltd., located in Hamilton, Bermuda.

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