New Drug Update - Vaxchora®

Jack MaoUniversity of Pittsburgh School of Pharmacy

PharmD Candidate, Class of 2017

Vaxchora®

• Live oral cholera vaccine• Manufacturer: Paxvax, Inc.• Approved by FDA in June 2016

Dosing/Route of Administration

• Dose: Single dose (100 mL of reconstituted suspension)• Route of administration: oral

Pharmacology

• Therapeutic class: vaccine• Mechanism of action• Live attenuated vaccine• Vaccine strain in Vaxchora® creates an incomplete, nontoxic version of

the cholera toxin• Vaxchora® live attenuated cholera bacteria replicate in the

gastrointestinal tract, which stimulates immune response (creation of antigen-specific antibodies against strain), providing immunity against cholera bacteria

• Reason for introduction• Approved for active immunization against disease caused by Vibrio

cholerae serogroup O1 (no protection against O139 or other non-O1 groups)

• Approved for use in adults 18 through 64 years of age traveling to cholera-affected areas

Therapeutic Information

• Indications• Vibrio cholerae serogroup O1 prophylaxis

• Unlabeled uses• No uses off-label

Contraindications/Precautions

• Contraindications• Severe hypersensitivity (anaphylaxis) to oral cholera vaccine

components or to a previous dose of any cholera vaccine

Contraindications/Precautions (cont.)• Precautions• Immunologic response may be diminished in

immunocompromised patients• Caution use in patients with immunocompromised close

contacts; transmission of vaccine strain to non-vaccinated close contacts may occur through stool shedding from the recipient for at least 7 days

Adverse Effects

• Fatigue (31.3%)• Headache (28.9%)• Abdominal pain (18.7%)• Nausea/vomiting (18.3%)• Lack of appetite (16.5%)• Diarrhea (3.9%)• Fever (0.6%)

Drug Interactions

• Chemotherapeutic agents (i.e. cisplatin, axitinib, afatinib, etc.) for irradiation, antimetabolites, alkylating agents, cytotoxic drugs, corticosteroids (i.e. prednisone, prednisolone, dexamethasone; when used in greater than physiologic doses)• Increased risk of infection by live vaccine due to decreased immune

response• Those whose disease is in remission, have restored immunocompetence,

and have discontinued chemotherapy for at least 3 months are eligible to receive

• Systemic antibiotics (i.e. azithromycin, cefazolin, cefixime, cefoxitin, etc.)• Prevent sufficient degree of multiplication of vaccine strain bacteria to occur

in order to induce protective immune response • Do not administer Vaxchora® to patients who have received oral or

parenteral antibiotics within 14 days prior to vaccination.

Drug Interactions (cont.)

• Chloroquine (antimalarial prophylaxis)• Decreased immune response when administered concurrently

with Vaxchora®• Administer Vaxchora® at least 10 days before beginning

chloroquine

Renal/Hepatic Adjustment

• No renal/hepatic adjustment necessary

Monitoring Parameters

• Have not been established at this time (further post-marketing follow-up studies needed to determine)

Patient Education

• Prevents cholera• Side effects may include tiredness, headache, lack of appetite,

abdominal pain, nausea/vomiting/diarrhea• Prevent transmission of vaccine strain to close contacts by

thoroughly washing hands after using the bathroom and before preparing or handling food for at least 14 days after dose

• Take drug at least 60 minutes before or 60 minutes after food & drinks.

• Call your doctor right away should you experience any of these symptoms (allergic reaction to drug):• Itching or hives, swelling in face or hands, swelling or tingling in

mouth or throat, chest tightness, trouble breathing

Patient Education (cont.)

• If you are pregnant while taking this vaccine, register for the pregnancy registry by calling 1-800-533-5899

• Exercise caution regarding food and water consumed in cholera-affected areas in accordance with recommendations from the Centers for Disease Control & Prevention for the prevention of cholera in travelers (https://www.cdc.gov/cholera/prevention.html)

Primary literature – Study 2

• Two studies cited in FDA approval/package insert to support use

• One was efficacy study (Study 2)• Randomized, double-blind study saline placebo-controlled V.

cholerae challenge study• 197 subjects ages 18-45 with no prior history of cholera infection

or travel to cholera-endemic area in previous 5 years randomized in 1:1 ratio to receive Vaxchora® or placebo (95 Vaxchora® recipients, 102 placebo recipients after randomization)

• Subjects admitted to inpatient unit, had nothing by mouth from midnight before ingestion of challenge strain (except water and 120 mL sodium bicarbonate buffer 1 minute prior to strain ingestion), and had nothing by mouth 90 minutes after ingestion of challenge strain

Primary literature – Study 2 (cont.)• Challenge consisted of 1 x 105 CFU live wild type V-cholerae El Tor

Inaba N16961 in 30 mL NaHCO3 buffer• Challenges split into 2 cohorts of either 10-day or 3 month challenges;

primary objective: demonstrate efficacy of single Vaxchora® dose in prevention of moderate to severe diarrhea following challenge at 10 days and 3-months post vaccination

• Severe diarrhea criteria• Defined as cumulative diarrhea purge ≥ 3 L within 10 days after

challenge• Diarrheal stool • Defined as ≥ 2 unformed stools (takes shape of container) in 48-hr

period ≥ 200 g or single unformed stool ≥ 300 g• Vaxchora® recipients challenged at 10 days and 3 months

compared with pooled group of placebo saline recipients challenged at 10 days and 3 months

Primary literature – Study 2 (cont.)• Of 95 Vaxchora® recipients, 68 were challenged; 35 were

challenged at 10 days, 33 at 3 months post-vaccination• Of 102 placebo recipients, 66 were challenged; 33 at 10 days,

33 at 3 months post vaccination• Vaccine efficacy against occurrence of moderate to severe

diarrhea• At 10 days: 90.3 % [95% CI 62.7%, 100.0%]• At 3 months: 79.5% [95% CI 49.9%, 100.0%]

Primary literature – Study 2 addendum

Primary literature 2 – Study 1+4• Study 1• Conducted in U.S. and Australia – a randomized double-blind,

saline placebo-controlled safety + immunogenicity study• 3146 subjects ages 18-45 not previously exposed to cholera

randomized 8:1 to receive 1 dose of Vaxchora® or placebo• Study 4• Conducted in U.S. – a randomized, double-blind, saline placebo-

controlled and immunogenicity study• 398 subjects ages 46-64 with no prior history of cholera infection

or travel to cholera-endemic area in previous 5 years randomized 3:1 to receive 1 dose of Vaxchora or placebo

• Primary endpoint was seroconversion rate at 10 days post-vaccination measured using a vibriocidal antibody assay (Inaba)

Results – Study 1+4

Cost• List Retail Price $225 per dose • Wholesale Acquisition Cost (if part of the Big Three:

AmeriSource Bergen, Cardinal, McKesson): $191.25 per dose• If buying 3+ doses in one order, shipping cost of $25 is waived

Sources• Cholera vaccine, live. Micromedex Solutions. Truven Health

Analytics, Inc. Ann Arbor, MI. Available at: http://www.micromedex.com. Accessed December 14, 2016.

• Vaxchora® [package insert]. Redwood City, CA: Paxvax Inc; 2016.

Any questions?