The U.S. Food and Drug Administration (FDA) has approved CAPVAXIVE™ (Pneumococcal 21-valent Conjugate Vaccine), Merck's innovative vaccine specifically designed to protect adults against the serotypes that cause the majority of invasive pneumococcal disease (IPD) cases. The approval follows the FDA's Priority Review of Merck's application.
CAPVAXIVE is indicated for active immunization to prevent invasive disease and pneumonia caused by Streptococcus pneumoniae in individuals 18 years of age and older. The vaccine targets 21 serotypes: 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15B, 15C, 16F, 17F, 19A, 20A, 22F, 23A, 23B, 24F, 31, 33F, and 35B.
Broader Coverage Than Existing Vaccines
What distinguishes CAPVAXIVE is its inclusion of eight unique serotypes not covered by other currently approved pneumococcal vaccines: 15A, 15C, 16F, 23A, 23B, 24F, 31, and 35B. According to CDC data from 2018-2021, these unique serotypes were responsible for approximately 27% of IPD cases in adults 50 years of age and older and approximately 30% in adults 65 years of age and older.
Based on the same CDC data, the serotypes covered by CAPVAXIVE are responsible for more cases of IPD in adults compared to PCV20 (pneumococcal 20-valent conjugate vaccine):
- In adults 50 years of age and older, CAPVAXIVE covers serotypes responsible for approximately 84% of IPD cases, compared to approximately 52% covered by PCV20
- In adults 65 years of age and older, CAPVAXIVE covers serotypes responsible for approximately 85% of IPD cases, compared to approximately 51% covered by PCV20
"Complications from invasive pneumococcal disease can lead to hospitalization, organ damage and even death. Many cases of adult disease are caused by serotypes not included in other approved pneumococcal conjugate vaccines," said Dr. Walter Orenstein, professor emeritus of medicine, epidemiology, global health and pediatrics at Emory University and member of Merck's Scientific Advisory Committee.
Clinical Data Supporting Approval
The approval is supported by data from multiple Phase 3 clinical studies evaluating CAPVAXIVE's safety and immunogenicity in various adult populations:
STRIDE-3 Trial
This double-blind study evaluated CAPVAXIVE compared to PCV20 in adults who had not previously received a pneumococcal conjugate vaccine. Key findings included:
- In adults 50 years and older, CAPVAXIVE was non-inferior to PCV20 for the 10 serotype polysaccharides shared with both vaccines
- CAPVAXIVE was superior to PCV20 for 10 of 11 serotype polysaccharides included in CAPVAXIVE but not in PCV20
- In adults 18-49 years, CAPVAXIVE elicited non-inferior immune responses compared to individuals 50-64 years
- CAPVAXIVE demonstrated a safety profile comparable to PCV20
STRIDE-5 Trial
This study evaluated CAPVAXIVE when administered concomitantly or sequentially with quadrivalent influenza vaccine (QIV) in adults 50 years and older. Results showed:
- CAPVAXIVE administered concomitantly with QIV was non-inferior to sequential administration for 20 of 21 serotypes
- Similar rates and severity of adverse reactions when CAPVAXIVE was administered with or without QIV
STRIDE-6 Trial
This study evaluated CAPVAXIVE in adults 50 years and older who had previously received pneumococcal vaccines. The trial showed:
- CAPVAXIVE elicited comparable or higher immune responses compared to other pneumococcal vaccines across different cohorts of previously vaccinated individuals
- Similar safety profile to both PCV15 and PPSV23
Safety Profile
The most commonly reported adverse reactions in individuals 18-49 years who received 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%).
In individuals 50 years and older, the most common adverse reactions were injection-site pain (41.2%), fatigue (19.7%), and headache (11.0%).
Expert Perspectives
"Today's approval is a testament to our population-specific strategy behind CAPVAXIVE, which demonstrated robust immunogenicity in a range of adult populations and is driven by a deep understanding of pneumococcal disease," said Dr. Dean Y. Li, president of Merck Research Laboratories. "We are proud to provide CAPVAXIVE as a new option specifically designed to help protect against the majority of invasive pneumococcal disease-causing serotypes in adults."
Next Steps
CAPVAXIVE is administered as a single dose. The U.S. Centers for Disease Control and Prevention's (CDC) Advisory Committee on Immunization Practices (ACIP) is expected to meet later this month to discuss and make recommendations for the use of CAPVAXIVE in adults.
The indication for the prevention of pneumonia caused by the specified S. pneumoniae serotypes is approved under accelerated approval based on immune responses as measured by opsonophagocytic activity (OPA). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
About Pneumococcal Disease
Pneumococcal disease is an infection caused by Streptococcus pneumoniae bacteria, with approximately 100 different serotypes that can affect adults differently than children. The disease can be invasive (bacteremia, bacteremic pneumonia, meningitis) or non-invasive (pneumonia confined to the lungs).
Pneumococcal pneumonia is the most common clinical presentation of pneumococcal disease in adults, with an estimated 150,000 adults hospitalized annually in the U.S. due to this condition.
CAPVAXIVE represents a significant advancement in adult pneumococcal vaccination, offering broader coverage against serotypes responsible for the majority of invasive pneumococcal disease in adults.
