IMVANEX Suspension for injection Ref.[28029] Active ingredients: Smallpox, live attenuated

Pharmacotherapeutic group: Vaccine, other viral vaccines
ATC code: J07BX

Efficacy in animals

Non-human primate (NHP) studies have demonstrated that vaccination with IMVANEX induced a comparable immune response and protective efficacy to traditional smallpox vaccines used to eradicate smallpox and protected NHP from severe disease associated with a lethal challenge of monkeypox virus. As seen with traditional smallpox vaccines, a significant reduction in both mortality and morbidity (viral load, weight loss, number of pox lesions, etc.) compared to non-vaccinated controls was demonstrated for NHP vaccinated with IMVANEX.

Immunogenicity

Seroconversion rates in Vaccinia-naïve healthy and special populations

The Vaccinia-naïve study population included healthy individuals as well as individuals with HIV infection and AD who received 2 doses of IMVANEX 4 weeks apart. Seroconversion rates in Vaccinia-naïve individuals were defined as appearance of antibody titers equal or greater than the assay cut-off value following receipt of two doses of IMVANEX. Seroconversion by ELISA and PRNT were as follows:

¹ Day 7/14 corresponding to 1 or 2 weeks after the first IMVANEX dose (analysis time point at Day 7 only in studies POXMVA-008 and POX-MVA-011; POX-MVA-005 had the first post vaccination analysis at Day 14); Day 28 corresponding to 4 weeks after the first IMVANEX dose; Day 42 corresponding to 2 weeks following the second dose of IMVANEX; SCR = Seroconversion rate;
² Full Analysis Set (FAS) (for POX-MVA-013: Immunogenicity Analysis Set; IAS);
³ Per Protocol Analysis Set (PPS),
⁴ seropositivity rates,
⁵ no immunogenicity sample taken,
⁶ combined Groups 1-3

Seroconversion rates in Vaccinia-experienced healthy and special populations

Seroconversion in Vaccinia-experienced individuals was defined as at least a two-fold increase in base titres following a single vaccination with IMVANEX.

¹ Day 0 corresponding to day of vaccination with IMVANEX; Day 7/14 corresponding to 1 or 2 weeks after vaccination with IMVANEX (first post vaccination analysis at Day 7 in study POX-MVA-011, and at Day 14 in studies POX-MVA-005 and POX-MVA-024); Day 28 corresponding to 4 weeks after vaccination with IMVANEX; SCR = Seroconversion rate; 2 Full Analysis Set (FAS);

Long-term immunogenicity in humans

Limited data on long-term immunogenicity covering a period of 24 months following primary vaccination of Vaccinia-naïve individuals with IMVANEX are currently available as shown below:

ELISA = enzyme-linked immunosorbent assay; GMT= geometric mean titre; N = number of subjects in the specific study group; PRNT = plaque reduction neutralisation test; SCR = seroconversion rate;
^* represents seropositivity rates

Booster Dose

Two clinical studies have demonstrated that IMVANEX is able to boost a pre-existing immunological memory response, induced by either licensed smallpox vaccines a long time ago or two years after IMVANEX.

¹ Day 0 corresponding to day of booster vaccination with IMVANEX (pre-booster); Day 7 and 14 corresponding to 1 or 2 weeks after booster vaccination with IMVANEX; N = number of subjects in the specific study group; ELISA = enzymelinked immunosorbent assay; PRNT = plaque reduction neutralization test; S+ = Seropositivity rate; GMT = geometric mean titre.

Immunogenicity and attenuation of take of ACAM2000 in healthy subjects

Imvanex was compared to ACAM2000 (a ‘second generation’ live attenuated smallpox vaccine produced in cell culture and licenced in the United States of America) in a randomized, open-label non-inferiority clinical trial in healthy adults (US military personnel) aged 18 to 42 years and who were naïve to smallpox vaccine (Study POX-MVA-006).

A total of 433 subjects were randomized in a 1:1 ratio to receive either two doses of Imvanex followed by a single dose of ACAM2000 at four weeks intervals or to receive a single dose of ACAM2000. ACAM2000 was administered via scarification.

The first co-primary endpoint compared vaccinia-specific neutralizing antibody responses at the peak visits (Day 42 after first vaccination for Imvanex where the subjects received two doses according to the standard vaccination schedule and Day 28 for ACAM2000). Imvanex induced a peak neutralizing antibody geometric mean titer (GMT) of 153.5 (n=185; 95% CI 134.3, 175.6), which was noninferior to the GMT of 79.3 (n=186; 95% CI 67.1, 93.8) obtained after scarification with ACAM2000.

The second co-primary endpoint evaluated if vaccination with Imvanex (n=165) prior to administration of ACAM2000 results in an attenuation of the cutaneous reaction to ACAM2000 (n=161) as measured by maximum lesion area in mm². At day 13-15, the median maximum lesion area for subjects who were administered ACAM2000 was 75mm² (95% CI 69.0, 85.0) and for those who received Imvanex it was 0.0 (95% CI 0.0, 2.0).

Paediatric population

The European Medicines Agency has deferred the obligation to submit the results of studies with IMVANEX in all subsets of the paediatric population for prevention of smallpox infection by active immunisation against smallpox infection and disease (see section 4.2 for information on paediatric use).

This medicinal product has been authorised under ‘exceptional circumstances’. This means that because of the lack of smallpox disease in the world it has not been possible to obtain complete information on this medicinal product. The European Medicines Agency will review any new information which may become available every year and this SmPC will be updated as necessary.