Regulatory Decision Summary for Capvaxive

Capvaxive is a 21-valent pneumococcal conjugate vaccine (21-valent PCV). The purpose of this New Drug Submission (NDS) was to obtain market authorization, pursuant to section C.08.004 of the Food and Drugs Regulations, for Capvaxive, filed by Merck Canada Inc. This submission was filed under the Priority Review Policy.

After evaluation of the submitted data package, Health Canada authorized Capvaxive for the indication of active immunization for the prevention of invasive pneumococcal disease (including sepsis, meningitis, bacteremic pneumonia, pleural empyema and bacteremia) caused by Streptococcus pneumoniae serotypes (3, 6A, 6C, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15B, 15C, 16F, 17F, 19A, 20A, 22F, 23A, 23B, 24F, 31, 33F, and 35B) in adults 18 years of age and older.

Capvaxive is a pneumococcal conjugate vaccine (21-valent PCV) indicated for the prevention of invasive pneumococcal disease (IPD) caused by Streptococcus pneumoniae serotypes contained in the vaccine in adults 18 years of age and older. The vaccine was designed to provide broader IPD coverage against the key serotypes, including 8 unique serotypes not contained in any currently licensed vaccines in Canada.

The immunogenicity and safety of the vaccine was demonstrated in the pivotal phase 3 Study P003 in pneumococcal vaccine-naïve adults 18 years of age and older. The vaccine effectiveness in adults against invasive pneumococcal disease was evaluated based on comparative immunogenicity to the licensed pneumococcal vaccine Prevnar 20 (PCV20), assessed by serotype specific opsonophagocytic activity (OPA) and immunoglobulin G (IgG) responses at 1-month postvaccination.

The clinical study showed that a single dose of Capvaxive can be given to adults who have been vaccinated with other pneumococcal vaccines at least 1 year prior.

In terms of safety, 4,500 adult patients received Capvaxive and the pooled safety information was sufficient to support the authorization of Capvaxive. The most commonly reported (˃10%) solicited adverse reactions in individuals 18 to 49 years of age following vaccination with Capvaxive were: injection‑site pain (73.1%), fatigue (36.0%), headache (27.5%), myalgia (16.4%), injection‑site erythema (13.8%), and injection‑site swelling (13.3%). The most commonly reported (˃10%) solicited adverse reactions in individuals 50 years of age and older who received Capvaxive were: injection‑site pain (41.2%), fatigue (19.7%), and headache (11.0%). Across the Phase 3 studies in individuals 18 years of age and older, the majority of local and systemic solicited adverse reactions were mild (based on intensity or size) and of short duration (≤3 days) severe events (defined as an event that prevents normal daily activity or size ˃10 cm) occurred in ≤1.0% of adults. Unsolicited events were reported by 7.8% in the Capvaxive group, and 6.1% in the control group. Apart from that, there is no specific concern based on the overall proportions of AEs in the Capvaxive when compared to the control group based on this information. Less common adverse reaction include: Lymphadenopathy, diarrhea, nausea, injection-site pruritus, chills and dizziness. The difference in reported serious adverse events (SAEs) was minimal; there were two events related to the vaccine: bronchospasm and injection-site cellulitis. There were 9 deaths in the integrated population. None of the deaths were considered to be related to study vaccine.

Overall, Capvaxive was well tolerated in adults ≥18 years of age with and without prior pneumococcal vaccination, with a safety profile generally comparable to the safety profile of other currently licensed pneumococcal vaccines.

An updated Risk Management Plan (RMP) for Capvaxive was reviewed by Health Canada and considered acceptable.

The chemistry and manufacturing information submitted for Capvaxive has demonstrated that the drug substance and drug product can be consistently manufactured to meet the approved specifications.

Following review and requested revisions, the final labelling and Product Monograph were considered to be acceptable.

Overall, the benefit-harm-uncertainty profile was favourable for Capvaxive for the approved indication when used under the conditions of use recommended in the approved Product Monograph. Therefore, a Notice of Compliance (NOC) was recommended.

For further details about Capvaxive, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.