Label: JYNNEOS- vaccinia virus modified strain ankara-bavarian nordic non-replicating antigen injection, suspension
- NDC Code(s): 50632-001-01, 50632-001-02
- Packager: Bavarian Nordic A/S
- Category: VACCINE LABEL
- DEA Schedule: None
- Marketing Status: Biologic Licensing Application
Updated August 31, 2022
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HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use JYNNEOS safely and effectively. See full prescribing information for JYNNEOS.
JYNNEOS (Smallpox and Monkeypox Vaccine, Live, Non-replicating) suspension for subcutaneous injection
Initial U.S. Approval: 2019
INDICATIONS AND USAGE
JYNNEOS is a vaccine indicated for prevention of smallpox and monkeypox disease in adults 18 years of age and older determined to be at high risk for smallpox or monkeypox infection. (1)
DOSAGE AND ADMINISTRATION
DOSAGE FORMS AND STRENGTHS
Suspension for injection. Each dose (0.5 mL) is supplied in a single-dose vial. (3)
- In smallpox vaccine-naïve healthy adults, the most common (> 10%) solicited injection site reactions were pain (84.9%), redness (60.8%), swelling (51.6%), induration (45.4%), and itching (43.1%); the most common solicited systemic adverse reactions were muscle pain (42.8%), headache (34.8%), fatigue (30.4%), nausea (17.3%) and chills (10.4%). (6.1)
- In healthy adults previously vaccinated with a smallpox vaccine, the most common (> 10%) solicited injection site reactions were redness (80.9%), pain (79.5%), induration (70.4%), swelling (67.2%), and itching (32.0%); the most common solicited systemic adverse reactions were fatigue (33.5%), headache (27.6%), and muscle pain (21.5%). (6.1)
- The frequencies of solicited local and systemic adverse reactions among adults with HIV-infection and adults with atopic dermatitis were generally similar to those observed in healthy adults. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Bavarian Nordic at toll-free phone 1-800-675-9596 or VAERS at 1-800-822-7967 or www.vaers.hhs.gov.
See 17 for PATIENT COUNSELING INFORMATION.
Table of Contents
FULL PRESCRIBING INFORMATION: CONTENTS*
- Sections or subsections omitted from the full prescribing information are not listed.
- 1 INDICATIONS AND USAGE
2 DOSAGE AND ADMINISTRATION
For subcutaneous injection only.
2.2 Preparation and Administration
Allow the vaccine to thaw and reach room temperature before use. Once thawed, the vaccine may be kept at +2°C to +8°C (+36°F to +46°F) for 8 weeks. Do not refreeze.
When thawed, JYNNEOS is a milky, light yellow to pale white colored suspension.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. If either of these conditions exists, the vaccine should not be administered.
Swirl the vial gently before use for at least 30 seconds. Withdraw a dose of 0.5 mL into a sterile syringe for injection.
Administer JYNNEOS by subcutaneous injection, preferably into the upper arm (deltoid).
- 3 DOSAGE FORMS AND STRENGTHS
5 WARNINGS AND PRECAUTIONS
5.1 Severe Allergic Reactions
Appropriate medical treatment must be available to manage possible anaphylactic reactions following administration of JYNNEOS.
Persons who experienced a severe allergic reaction following a previous dose of JYNNEOS or following exposure to any component of JYNNEOS may be at increased risk for severe allergic reactions after JYNNEOS. The risk for a severe allergic reaction should be weighed against the risk for disease due to smallpox or monkeypox.
5.2 Altered Immunocompetence
Immunocompromised persons, including those receiving immunosuppressive therapy, may have a diminished immune response to JYNNEOS.
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a vaccine cannot be directly compared with rates in the clinical trials of another vaccine, and may not reflect the rates observed in practice. There is the possibility that broad use of JYNNEOS could reveal adverse reactions not observed in clinical trials.
The overall clinical trial program included 22 studies and a total of 7,859 individuals 18 through 80 years of age who received at least 1 dose of JYNNEOS (7,093 smallpox vaccine-naïve and 766 smallpox vaccine-experienced individuals).
Solicited Adverse Reactions
Solicited Adverse Reactions in Smallpox Vaccine-Naïve Individuals:
The safety of JYNNEOS in smallpox vaccine-naïve individuals was evaluated in Study 1 , a randomized, double-blind, placebo-controlled study conducted in the US in which vaccinia-naïve adults ages 18 to 40 years received either two doses of JYNNEOS (N=3003), or two injections of Tris-Buffered Saline (placebo, N=1002) four weeks apart.
In the total study population, the mean age was 28 years; 47.9% of the subjects were men; 77.4% were white/Caucasian, 17.8% black/African American, 1.9% Asian, 0.5% American Indian/Alaska Native, 0.4% Native Hawaiian/Other Pacific, 1.9% other racial groups; and 11.4% of subjects were of Hispanic/Latino ethnicity. The demographic compositions of JYNNEOS and placebo groups were similar.
In Study 1, subjects were monitored for local and systemic adverse reactions using diary cards for an 8-day period starting on the day of each vaccination. The frequencies of solicited local and systemic adverse reactions following any dose of JYNNEOS are presented in Table 1.
Table 1: Percentages of Subjects with Solicited Local Injection Site Reactions and Systemic Adverse Reactions within 8 Days of Administration of Any Dose of JYNNEOS in Adults 18 to 40 Years of Age, Study 1x Reaction JYNNEOS
N = 980
a Grade 3 pain defined as spontaneously painful
b Grade 3 itching, muscle pain, headache, fatigue, nausea and chills defined as preventing routine daily activities
c Fever defined as oral temperature ≥ 100.4°F (≥ 38°C), Grade ≥ 3 fever defined as ≥ 102.2°F (≥ 39.0°C)
N=number of subjects
Local (Injection site)
Pain, Grade 3a
Redness ≥ 100 mm
Swelling ≥ 100 mm
Induration ≥ 100 mm
Itching, Grade 3b
Muscle Pain, Grade 3b
Headache, Grade 3b
Fatigue, Grade 3b
Nausea, Grade 3b
Chills, Grade 3b
Fever, Grade ≥3c
In Study 1, the majority of solicited local and systemic adverse reactions reported with JYNNEOS had a median duration of 1 to 6 days. In general, there were similar proportions of subjects reporting solicited local or systemic reactions of any severity after Dose 2 of JYNNEOS compared with Dose 1, with the exception of injection site pain, which was more commonly reported following Dose 1 (79.3%) than Dose 2 (69.9%).
Solicited Adverse Reactions in Persons Previously Vaccinated with a Smallpox Vaccine:
Three studies (Study 2, Study 3, and Study 4, [2-4]) conducted in the US and Germany evaluated the safety of JYNNEOS in 409 persons previously vaccinated with a smallpox vaccine who received one or two doses of JYNNEOS (mean age 39 years, range 20-80 years; 59% women; 98.8% white/Caucasian; 0.7% Asian; 0.5% black/African American). Subjects were monitored for local and systemic adverse reactions using diary cards for an 8-day period starting on the day of each vaccination. Across all three studies, solicited local adverse reactions reported following any dose of JYNNEOS were redness (80.9%), pain (79.5%), induration (70.4%), swelling (67.2%), and itching (32.0%) at the injection site; solicited systemic adverse reactions reported following any dose of JYNNEOS were fatigue (33.5%), headache (27.6%), muscle pain (21.5%), nausea (9.8%), chills (0.7%), and fever (0.5%).
Solicited Adverse Reactions in HIV-infected Individuals:
The safety of JYNNEOS in HIV-infected individuals was evaluated in Study 5 , an open label trial conducted in the US that included 351 HIV-infected smallpox vaccine-naïve subjects, 131 HIV-infected subjects who previously received smallpox vaccine, 88 non-HIV-infected smallpox vaccine-naïve subjects and 9 non-HIV-infected subjects who had previously received a smallpox vaccine. The racial/ethnic and gender compositions of HIV-infected smallpox vaccine-naïve subjects and those who had previously received smallpox vaccine were similar and overall were 17.0% women; 45.8% white/Caucasian; 0.4% Asian; 33.2% black/African American; 19.0% Hispanic/Latino ethnicity; the HIV-infected smallpox vaccine-naïve group tended to be younger (mean age 37 years) compared to those who had previously received a smallpox vaccine (mean age 45 years). Subjects had CD4 counts ≥ 200 and ≤ 750 cells/µL at study entry.
Solicited local and systemic adverse reactions were reported at similar or lower frequencies in HIV-infected smallpox vaccine-naïve subjects as compared to those seen in non-HIV-infected smallpox vaccine-naïve individuals in this study.
In HIV-infected subjects with previous smallpox vaccine exposure, fever and chills were reported in 1.5% and 8.4% of subjects respectively. Frequencies of other solicited local and general adverse reactions in this population were similar to those reported in Studies 2-4 in non-HIV-infected subjects who had previously received smallpox vaccination.
Solicited Adverse Reactions in Individuals with Atopic Dermatitis:
The safety of JYNNEOS in smallpox vaccine-naïve subjects with currently active or a history of atopic dermatitis (AD) was evaluated in a multicenter, open-label clinical study (Study 6 ) conducted in the US and Mexico that included 350 subjects with AD and 282 subjects without AD. In the overall study the mean age of subjects was 27 years (range 18-42 years), and subjects were 59.0% women, 39.4% white/Caucasian, 10.9% Asian, 9.0% black/African American, 2.2% Other, and 38.4% Hispanic/Latino ethnicity. Demographic compositions were similar between subjects with and without AD. In subjects with AD, solicited local and systemic adverse reactions were reported at similar frequencies as those in subjects without AD in this study, with the exception of redness (61.2% with AD vs. 49.3% without AD), swelling (52.2% with AD vs. 40.8% without AD), chills (15.9% with AD vs. 7.8% without AD) and headache (47.2% with AD vs. 34.8% without AD).
Serious Adverse Events
The integrated analyses of serious adverse events (SAEs) pooled safety data across 22 studies, which included a total of 7,093 smallpox vaccine-naïve subjects and 766 smallpox vaccine-experienced subjects who received at least 1 dose of JYNNEOS and 1,206 smallpox vaccine-naïve subjects who received placebo only. SAEs were monitored from the day of the first study vaccination through at least 6 months after the last study vaccination.
Among the smallpox vaccine-naïve subjects, SAEs were reported for 1.5% of JYNNEOS recipients and 1.1% of placebo recipients. Among the smallpox vaccine-experienced subjects enrolled in studies without a placebo comparator, SAEs were reported for 2.3% of JYNNEOS recipients. Across all studies, a causal relationship to JYNNEOS could not be excluded for 4 SAEs, all non-fatal, which included Crohn’s disease, sarcoidosis, extraocular muscle paresis and throat tightness.
Cardiac Adverse Events of Special Interest
Evaluation of cardiac adverse events of special interest (AESIs) included any cardiac signs or symptoms, ECG changes determined to be clinically significant, or troponin-I elevated above 2 times the upper limit of normal. In the 22 studies, subjects were monitored for cardiac-related signs or symptoms through at least 6 months after the last vaccination.
The numbers of JYNNEOS and placebo recipients, respectively, with troponin-I data were: baseline level (6,376 and 1,203); level two weeks after first dose (6,279 and 1,166); level two weeks after second dose (1,683 and 193); unscheduled visit, including for clinical evaluation of suspected cardiac adverse events (500 and 60).
Cardiac AESIs were reported to occur in 1.3% (95/7,093) of JYNNEOS recipients and 0.2% (3/1,206) of placebo recipients who were smallpox vaccine-naïve. Cardiac AESIs were reported to occur in 2.1% (16/766) of JYNNEOS recipients who were smallpox vaccine-experienced. The higher proportion of JYNNEOS recipients who experienced cardiac AESIs was driven by 28 cases of asymptomatic post-vaccination elevation of troponin-I in two studies: Study 5, which enrolled 482 HIV-infected subjects and 97 healthy subjects, and Study 6, which enrolled 350 subjects with atopic dermatitis and 282 healthy subjects. An additional 127 cases of asymptomatic post-vaccination elevation of troponin-I above the upper limit of normal but not above 2 times the upper limit of normal were documented in JYNNEOS recipients throughout the clinical development program, 124 of which occurred in Study 5 and Study 6. Proportions of subjects with troponin-I elevations were similar between healthy and HIV-infected subjects in Study 5 and between healthy and atopic dermatitis subjects in Study 6. A different troponin assay was used in these two studies compared to the other studies, and these two studies had no placebo controls. The clinical significance of these asymptomatic post-vaccination elevations of troponin-I is unknown.
Among the cardiac AESIs reported, 6 cases (0.08%) were considered to be causally related to JYNNEOS vaccination and included tachycardia, electrocardiogram T wave inversion, electrocardiogram abnormal, electrocardiogram ST segment elevation, electrocardiogram T wave abnormal, and palpitations.
None of the cardiac AESIs considered causally related to study vaccination were considered serious.
8 USE IN SPECIFIC POPULATIONS
All pregnancies have a risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Available human data on JYNNEOS administered to pregnant women are insufficient to inform vaccine-associated risks in pregnancy.
The effect of JYNNEOS on embryo-fetal and post-natal development was evaluated in four developmental toxicity studies conducted in female rats and rabbits. In two studies, rats were administered a single human dose of JYNNEOS (0.5 mL) once prior to mating and on one or two occasions during gestation. In the third study, rats were administered a single human dose of JYNNEOS (0.5 mL) on two occasions during gestation. In the fourth study, rabbits were administered a single human dose of JYNNEOS (0.5 mL) once prior to mating and on two occasions during gestation. These animal studies revealed no evidence of harm to the fetus [see Data].
Developmental toxicity studies were conducted in female rats and rabbits. In one study, female rabbits were administered a single human dose of JYNNEOS (0.5 mL) by the subcutaneous route on three occasions: prior to mating, and on gestation days 0 and 14. Three studies were conducted in female rats administered a single human dose of JYNNEOS (0.5 mL) by the subcutaneous route on two or three occasions: prior to mating, and on gestation days 0 and 14; or prior to mating, and on gestation day 0; or on gestation days 0 and 6. No vaccine-related fetal malformations or variations and adverse effects on female fertility or pre-weaning development were reported in these studies.
It is not known whether JYNNEOS is excreted in human milk. Data are not available to assess the effects of JYNNEOS in the breastfed infant or on milk production/excretion.
The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for JYNNEOS and any potential adverse effects on the breastfed child from JYNNEOS or from the underlying maternal condition. For preventive vaccines, the underlying condition is susceptibility to disease prevented by the vaccine.
8.4 Pediatric Use
Safety and effectiveness of JYNNEOS have not been established in individuals less than 18 years of age.
When thawed, JYNNEOS (Smallpox and Monkeypox Vaccine, Live, Non replicating) is a milky, light yellow to pale white colored suspension for subcutaneous injection.
JYNNEOS is a live vaccine produced from the strain Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN), an attenuated, non-replicating orthopoxvirus. MVA-BN is grown in primary Chicken Embryo Fibroblast (CEF) cells suspended in a serum-free medium containing no material of direct animal origin, harvested from the CEF cells, purified and concentrated by several Tangential Flow Filtration (TFF) steps including benzonase digestion. Each 0.5 mL dose is formulated to contain 0.5 x 108 to 3.95 x 108 infectious units of MVA-BN live virus in 10 mM Tris (tromethamine), 140 mM sodium chloride at pH 7.7. Each 0.5 mL dose may contain residual amounts of host-cell DNA (≤ 20 mcg), protein (≤ 500 mcg), benzonase (≤ 0.0025 mcg), gentamicin (≤ 0.400 mcg) and ciprofloxacin (≤ 0.005 mcg).
JYNNEOS is a sterile vaccine formulated without preservatives. The vial stoppers are not made with natural rubber latex.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
JYNNEOS is an attenuated, live, non-replicating smallpox and monkeypox vaccine that elicits humoral and cellular immune responses to orthopoxviruses. Vaccinia neutralizing antibody responses in humans were evaluated to establish the effectiveness of JYNNEOS for prevention of smallpox and monkeypox.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
JYNNEOS has not been evaluated for carcinogenic or mutagenic potential, or for impairment of male fertility in animals. Developmental toxicity studies conducted in rats and rabbits vaccinated with JYNNEOS revealed no evidence of impaired female fertility [see Use in Specific Populations (8.1)].
13.2 Animal Toxicology and/or Pharmacology
The efficacy of JYNNEOS to protect cynomolgus macaques (Macaca fascicularis) against a monkeypox virus (MPXV) challenge was evaluated in several studies. Animals were administered Tris-Buffered Saline (placebo) or JYNNEOS (1 x 108 TCID50) subcutaneously on day 0 and day 28. On day 63, animals were challenged with MPXV delivered by aerosol (3 x 105 pfu), intravenous (5 x 107 pfu) or intratracheal (5 x 106 pfu) route. Across all studies, 80-100% of JYNNEOS-vaccinated animals survived compared to 0-40% of control animals.
14 CLINICAL STUDIES
14.1 Vaccine Effectiveness
Vaccine effectiveness against smallpox was inferred by comparing the immunogenicity of JYNNEOS to a licensed smallpox vaccine (ACAM2000) based on a Plaque Reduction Neutralization Test (PRNT) using the Western Reserve strain of vaccinia virus and was supported by efficacy data from animal challenge studies. [see Nonclinical Toxicology (13.2)]
Vaccine effectiveness against monkeypox was inferred from the immunogenicity of JYNNEOS in a clinical study and from efficacy data from animal challenge studies. [see Nonclinical Toxicology (13.2)]
Study 7  (N=433) was a randomized, open-label study conducted at US military facilities in South Korea to compare the immunogenicity of JYNNEOS to ACAM2000 in healthy smallpox vaccine-naïve adults 18 through 42 years of age. Subjects were randomized to receive either two doses of JYNNEOS (N=220) administered 28 days apart or one dose of ACAM2000 (N=213). In the total study population, the mean age was 24 years and 23 years in subjects receiving JYNNEOS and ACAM2000, respectively; 82.3% and 86.4% of the subjects were men; 57.3% and 63.8% were white/Caucasian, 21.8% and 18.8% black/African American, 6.4% and 5.6% Asian, 3.6% and 2.8% American Indian/Alaska Native, 2.3% and 1.4% Native Hawaiian/Other Pacific, 8.6% and 7.5% other racial groups, and 24.5% and 18.8% of Hispanic/Latino ethnicity (JYNNEOS and ACAM2000, respectively).
The primary immunogenicity endpoint was geometric mean titer (GMT) of vaccinia neutralizing antibodies assessed by PRNT at “peak visits” defined as two weeks after the second dose of JYNNEOS and four weeks after the single dose of ACAM2000. Analyses of antibody responses were performed in the per-protocol immunogenicity (PPI) population, consisting of individuals who received all vaccinations and completed all visits up until the peak visit without major protocol violations pertaining to immunogenicity assessments. Table 2 presents the pre-vaccination and “peak visit” PRNT GMTs from Study 7.
Table 2: Comparison of Vaccinia-Neutralizing Antibody Responses Following Vaccination with JYNNEOS or ACAM2000 in Healthy Smallpox Vaccine-Naïve Adults 18 through 42 Years of Age, Study 7x, Per Protocol Set for Immunogenicityy Time Point JYNNEOSa (N=185)
GMTb [95% CI]
GMTb [95% CI]
y Per Protocol Set for Immunogenicity included subjects who received all vaccinations, completed all visits up until the specified “peak visits” (two weeks after the second dose of JYNNEOS or 4 weeks after the single dose of ACAM2000) without major protocol violations pertaining to immunogenicity assessments.
a JYNNEOS was administered as a series of two doses given 28 days apart, and ACAM2000 was administered as a single dose.
b GMT of vaccinia-neutralizing antibody titers assessed by plaque reduction neutralization test (PRNT) using the Western Reserve vaccinia strain. Values below the assay lower limit of quantitation (LLOQ) of 20 were imputed to a titer of 10; the proportions of subjects with pre-vaccination titers less than the assay lower limit of detection were 98.9% among subjects randomized to JYNNEOS and 97.8% among subjects randomized to ACAM2000, respectively.
c Non-inferiority of the “peak visit” PRNT GMT for JYNNEOS compared to ACAM2000 was demonstrated as the lower bound of the 1-sided 97.5% CI for the GMT ratio (JYNNEOS/ACAM2000) was > 0.5.
N: Number of subjects in the specified treatment group; GMT: Geometric Mean Titer; 95% CI: 95% confidence interval, lower limit and upper limit.
10.1 [9.9, 10.2]
10.0 [10.0, 10.0]
152.8c [133.3, 175.0]
84.4c [73.4, 97.0]
PRNT GMTs were also evaluated at pre-specified time points post-vaccination and prior to the “peak visits”. The PRNT GMTs at two and four weeks after the first dose of JYNNEOS (prior to the second dose), were 23.4 (95% CI: 20.5, 26.7) and 23.5 (95% CI: 20.6, 26.9), respectively. The PRNT GMT at two weeks after the single dose of ACAM2000 was 23.7 (95% CI: 20.9, 26.8).
- 15 REFERENCES
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1 How Supplied
Package of 20 single-dose vials (Package NDC number: 50632-001-02; Vial NDC number: 50632-001-01)
16.2 Storage Conditions
Keep frozen at -25°C to -15°C (-13°F to +5°F).
Store in the original package to protect from light.
Do not re-freeze a vial once it has been thawed.
Once thawed, the vaccine may be kept at +2°C to +8°C (+36°F to +46°F) for 8 weeks.
Do not use the vaccine after the expiration date shown on the vial label.
17 PATIENT COUNSELING INFORMATION
- Inform vaccine recipient of the potential benefits and risks of vaccination with JYNNEOS.
- Inform vaccine recipient of the importance of completing the two dose vaccination series.
- Advise vaccine recipient to report any adverse events to their healthcare provider or to the Vaccine Adverse Event Reporting System at 1-800-822-7967 and www.vaers.hhs.gov.
Bavarian Nordic A/S
- PRINCIPAL DISPLAY PANEL - Carton Label
- PRINCIPAL DISPLAY PANEL - Vial Label
INGREDIENTS AND APPEARANCE
vaccinia virus modified strain ankara-bavarian nordic non-replicating antigen injection, suspension
Product Information Product Type VACCINE Item Code (Source) NDC:50632-001 Route of Administration SUBCUTANEOUS Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength VACCINIA VIRUS MODIFIED STRAIN ANKARA-BAVARIAN NORDIC NON-REPLICATING ANTIGEN (UNII: TU8J357395) (VACCINIA VIRUS MODIFIED STRAIN ANKARA-BAVARIAN NORDIC NON-REPLICATING ANTIGEN - UNII:TU8J357395) VACCINIA VIRUS MODIFIED STRAIN ANKARA-BAVARIAN NORDIC NON-REPLICATING ANTIGEN 50000000 in 0.5 mL Inactive Ingredients Ingredient Name Strength TROMETHAMINE (UNII: 023C2WHX2V) SODIUM CHLORIDE (UNII: 451W47IQ8X) WATER (UNII: 059QF0KO0R) Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:50632-001-02 20 in 1 CARTON 1 NDC:50632-001-01 0.5 mL in 1 VIAL; Type 0: Not a Combination Product Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date BLA BLA125678 03/17/2021 Labeler - Bavarian Nordic A/S (310209754)