JYNNEOS Suspension for injection Ref.[50012] Active ingredients: Smallpox, live attenuated

Source: FDA, National Drug Code (US)  Revision Year: 2022 

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.

13.1. 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 × 108 TCID 50) subcutaneously on day 0 and day 28. On day 63, animals were challenged with MPXV delivered by aerosol (3 × 105 pfu), intravenous (5 × 107 pfu) or intratracheal (5 × 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)].

14.2 Immunogenicity

Study 7 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 PointJYNNEOSa (N=185)
GMTb [95% CI]
ACAM2000a (N=186)
GMTb [95% CI]
Pre-Vaccination 10.1 [9.9, 10.2] 10.0 [10.0, 10.0]
"Peak Visit"y
152.8c [133.3, 175.0] 84.4c [73.4, 97.0]

x NCT01913353
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.

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).

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