CAPVAXIVE™ (V116) Pneumococcal 21-valent Conjugate Vaccine Clinical Trials, Dosage, Indication, Side Effects
Merck's CAPVAXIVE™ (V116) (Pneumococcal 21-valent Conjugate Vaccine 21-valent (PVC21) prevents invasive pneumococcal disease (IPD) and pneumococcal pneumonia in adults. CAPVAXIVE is designed to address the serotypes that create adult pneumococcal disease, including eight unique serotypes: 15A, 15C, 16F, 23A, 23B, 24F, 31, and 35B. CAPVAXIVE utilizes the PeliCRM197® carrier protein, which helps enhance antigen immunogenicity in conjugate vaccines.
On June 17, 2024, the U.S. Food and Drug Administration (FDA) approved CAPVAXIVE (STN: BL 125814/0), specifically designed for adults and covers serotypes responsible for approximately 84% of invasive pneumococcal disease in adults 50 and older. Across four Phase 3 studies, CAPVAXIVE demonstrated robust immune responses in vaccine-naïve and vaccine-experienced adult populations.
On April 29, 2024, results from the STRIDE-10 Phase 3 trial study included V116 elicited immune responses that were noninferior compared to PPSV23 for the 12 serotypes common to both vaccines, as measured by serotype-specific opsonophagocytic activity (OPA) geometric mean titers (GMTs) at Day 30. Immune responses elicited by V116 were superior for the nine serotypes included in V116 but not PPSV23, as measured by OPA GMT ratios at Day 30, and superior for eight of nine serotypes unique to V116 compared to PPSV23, as measured by the proportions of participants with ≥4-fold rise in immune responses. V116 had a safety profile comparable to PPSV23. Merck also presented findings that suggest V116 may help to reduce the health and economic burden associated with invasive pneumococcal disease and non-bacteremic pneumococcal pneumonia among adults in France, Sweden, Spain, and the Netherlands.
On March 19, 2024, Merck announced across the clinical studies presented at the 13th Meeting of the International Society of Pneumonia and Pneumococcal Diseases, V116 was shown to be immunogenic for all 21 serotypes covered by the vaccine in a variety of adult populations, including those who had not previously received a pneumococcal vaccine (pneumococcal vaccine-naïve), those who had previously received a pneumococcal vaccine (pneumococcal vaccine-experienced) and those with an increased risk of pneumococcal disease, including people living with HIV. V116 also elicited higher immune responses than the studied comparators for the serotypes unique to V116 in all STRIDE studies presented at this meeting. In addition to Phase 3 clinical data on V116, Merck also presented preliminary data from the real-world evidence study ((Abstract #308)) on March 19, 2024, Pneumococcal Pneumonia Epidemiology, Urine Serotyping, and Mental Outcomes (PNEUMO), which found that among 2,065 adults 50 years of age and older hospitalized with community-acquired pneumonia between 2018 and 2022, 242 pneumococcal serotypes were detected. Of these serotypes, approximately 84% were covered by V116. About 25% of the detected serotypes were covered only by V116, not PCV15 or PCV20.
On October 16, 2024, key findings from the STRIDE-8 trial included: CAPVAXIVE was immunogenic for all 21 serotypes included in the vaccine, as measured by serotype-specific OPA geometric mean titers (GMTs) (primary immunogenicity objective) and immunoglobulin G geometric mean concentrations (GMCs) (secondary immunogenicity objective) at Day 30; Immune responses elicited by CAPVAXIVE were comparable to PCV15 followed by PPSV23 for the 13 common serotypes and higher for the eight serotypes unique to CAPVAXIVE, as measured by serotype-specific OPA GMTs and IgG GMCs 30 days post-vaccination; The proportions of participants with adverse events (AEs), including injection-site, systemic, and vaccine-related AEs, were numerically lower in the V116 + placebo group than in the PCV15 + PPSV23 group.
Merck, known as MSD outside of the United States and Canada, is unified around a purpose: We use the power of leading-edge science to save and improve lives worldwide. For more than four decades, Merck has been at the forefront of pneumococcal disease prevention through vaccination and remains committed to helping to protect people of all ages from this disease.
CAPVAXIVE Vaccine U.S. CDC ACIP
The U.S. Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) Work Group decided on October 23, 2024, to lower the age-based recommendation to include adults 50-64 years. The ACIP met on June 27, 2024, and reviewed these presentations: Economic analysis and public health impact of PCV21 use in adults, Mr. C Stoecker; Summary of three economic studies on the use of 21-valent pneumococcal conjugate vaccine (PCV21) among adults in the U.S.; Andrew J. Leidner, PhD; Summary of WG Interpretation of EtR and policy options on PCV21 use in adults and clinical guidance for implementation, Dr. M Kobayashi on February 29, 2024. Heather Platt, M.D., presented Key Results from the Phase 3 Clinical Development Program, which include, but are not limited to the following: V116 elicits robust immune responses to all 21 serotypes contained in the vaccine; is noninferior to PCV20 for all common serotypes and superior to PCV20 for 10 of 11 serotypes unique to V116 in pneumococcal vaccine-naïve adults ≥50 years of age; is immunogenic in pneumococcal vaccine experienced adults, regardless of the prior vaccine received; is immunogenic when administered concomitantly with inactivated influenza vaccine; and V116 is well-tolerated with a safety profile generally comparable to currently licensed pneumococcal vaccines. The initial assessment by the ACIP Work Group suggested that V116 provides broader serotype coverage than currently recommended vaccines for adults 65+ or immunocompromised adults. Miwako Kobayashi, M.D., presented the Work Group's proposed policy questions on lowering the age-based recommendation for pneumococcal vaccination to include adults aged 50-64. The ACIP is expected to vote in an upcoming meeting on whether V116 should be recommended as a pneumococcal vaccination option for U.S. adults. CDC recommendations follow FDA approval.
CAPVAXIVE Vaccine Indication
V116 is designed to be administered as a single dose to help prevent invasive pneumococcal disease and pneumococcal pneumonia in adults. It's estimated that over 150,000 adults are hospitalized from pneumococcal pneumonia each year in the U.S. The serotypes covered by V116 are responsible for approximately 83% of invasive pneumococcal disease in individuals 65 and older. Pneumococcal disease is an infection caused by bacteria called Streptococcus pneumoniae. There are more than 100 types (serotypes) of pneumococcal bacteria.
CAPVAXIVEV Vaccine Availability
As of June 17, 2024, CAPVAXIVE V116 was approved by the U.S. FDA (STN: BL 125814/0) and became available at health clinics and pharmacies in the U.S.
CAPVAXIVE V116 Vaccine News
October 16, 2024 - "Adults with chronic medical conditions, such as kidney disease or diabetes, are particularly vulnerable to invasive pneumococcal disease, which may increase their risk of severe illness," said Dr. Walter Orenstein, professor emeritus of medicine, epidemiology, global health and pediatrics at Emory University and member of Merck's Scientific Advisory Committee.
June 21, 2024 - Nature published a news brief - FDA approves 21-valent pneumococcal vaccine.
June 17, 2024 - Dr. Walter Orenstein, professor emeritus of medicine, epidemiology, global health, and pediatrics at Emory University and member of Merck's Scientific Advisory Committee, stated, "CAPVAXIVE is designed to include the serotypes that cause the majority of invasive pneumococcal disease in adults, helping to protect adults against invasive pneumococcal disease and pneumococcal pneumonia."
March 19, 2024 - "The extensive data presented this week reaffirm our confidence in the potential clinical value V116 could provide to a range of adult populations," said Dr. Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories, in a press release. "We are encouraged by the results of these studies showing that V116 has generated immune responses to the serotypes responsible for most adult invasive pneumococcal disease."
February 29, 2024 - James Loehr, MD, led a U.S. CDC vaccine committee review of V116.
July 28, 2022 - Merck presented positive results from the Phase 1/2 study for V116, Merck's investigational Pneumococcal 21-Valent Conjugate Vaccine designed to target serotypes that account for 85% of all invasive pneumococcal diseases in U.S. adults 65 years and older as of 2019, and enrolled the first patient into the Phase 3 STRIDE-3 trial evaluating V116 in vaccine-naïve adults. V116 contains eight serotypes not included in any currently licensed pneumococcal vaccine.
June 21, 2022 - Merck (NYSE: MRK) announced the presentation of positive results from the Phase 1/2 study, V116-001, evaluating the safety, tolerability, and immunogenicity of V116, the company's investigational 21-valent PCV, in pneumococcal vaccine-naïve adults 18-49 years of age (Phase 1) and 50 years of age and older (Phase 2).
April 14, 2022 - V116, Merck's investigational 21-valent pneumococcal conjugate vaccine, received Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) for the prevention of IPD and pneumococcal pneumonia caused by Streptococcus pneumoniae serotypes 3, 6A/C, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15B/C, 16F, 17F, 19A, 20, 22F, 23A, 23B, 24F, 31, 33F, 35B in adults 18 years of age and older.
V116 Vaccine Clinical Trials
Merck's 21-valent pneumococcal conjugate vaccine (PCV) has been in clinical trials since 2019. Multiple Phase 3 trials of V116 were initiated within the last 12 months, including STRIDE-3 (NCT05425732), STRIDE-6 (NCT05420961), STRIDE-7 (NCT05393037), STRIDE-4 (NCT05464420), STRIDE-5 (NCT05526716), and STRIDE-8 (NCT05696080).
Data from STRIDE-3 Sub-group (Abstract #379) - The sub-group analysis of the pivotal STRIDE-3 (NCT05425732) trial evaluated immunogenicity in adults 50 years of age and older who had not previously received a pneumococcal vaccine (Cohort 1) by age groups (50–64, 65–74 and 75–84 years) (n=2,362). Results found that V116 was immunogenic for all 21 vaccine serotypes across the studied age sub-groups, as assessed by serotype-specific OPA GMTs 30 days post-vaccination. There was a slight downward trend in immune responses in adults 65–74 and 75 years of age and older compared to adults of age. V116 had a safety profile comparable to PCV20. Results from the STRIDE-3 trial were presented at the World Vaccine Congress West Coast in November 2023.
Data from STRIDE-6 and STRIDE-6 Sub-group (Abstracts #353 and #520) - STRIDE-6 (NCT05420961) is a Phase 3 trial investigating V116 in adults 50 years of age and older who had previously received a pneumococcal vaccine at least one year prior (n=712). Participants were enrolled based on previous pneumococcal vaccination with PPSV23, PCV15, PCV13 (pneumococcal 13-valent conjugate vaccine), PPSV23+PCV13, PCV13+PPSV23 or PCV15+PPSV23, and received either V116, PCV15 or PPSV23.
Results showed that V116 was immunogenic across all cohorts, as assessed by OPA GMTs 30 days post-vaccination, and that V116 elicited comparable immune responses to the serotypes also covered by PCV15 and PPSV23 and higher immune responses for the serotypes covered only by V116. A STRIDE-6 sub-group analysis evaluating immunogenicity across all cohorts by time since prior pneumococcal vaccination found that V116 elicited comparable immune responses regardless of time since prior pneumococcal vaccination, including more than ten years post-vaccination with PPSV23 (n=56), and 5–9 years post-vaccination with either PPSV23 or other pneumococcal vaccines (n=208). In this study, V116 had a safety profile comparable to PCV15 and PPSV23.
Data from STRIDE-7 (Abstract #1093) - STRIDE-7 (NCT05393037) is Phase 3, a double-blind study of V116 in adults living with HIV (n=304). Results showed that V116 was immunogenic for all serotypes covered by the vaccine, as assessed by OPA GMTs and IgG GMCs 30 days post-vaccination. V116 elicited comparable immune responses to the comparator, PCV15+PPSV23, for all 13 shared serotypes and higher immune responses for the eight serotypes covered only by V116. Fewer participants experienced adverse events (AEs) with V116 (71.6%) compared with PCV15+PPSV23 (91%), primarily due to fewer injection-site AEs.
Data from STRIDE-9 (Abstract #1085) - STRIDE-9 (NCT05633992) is a Phase 3, randomized, double-blind, active-comparator controlled study, which investigated V116 in Japanese adults 65 years of age and older who had not previously received a pneumococcal vaccine (n=450). Serotype-specific OPA responses were measured at baseline and 30 days post-vaccination and results demonstrated that V116 elicited noninferior immune responses for the 12 serotypes shared with PPSV23 and serotype 15B (which is included in PPSV23 but not included in V116). V116 also elicited higher immune responses for the serotypes only covered by V116 and not PPSV23. V116 also had a comparable safety profile to PPSV23.
Data from PNEUMO U.S. Serotype Distribution Study (Abstract #308) - The PNEUMO U.S. study evaluated pneumococcal serotype distribution among adults 50 years of age and older hospitalized with community-acquired pneumonia (n=2,065), one of the non-invasive forms of pneumococcal disease, between 2018 and 2022 in three hospitals in Tennessee and Georgia. Urine samples from patients were evaluated for antigens from 30 pneumococcal serotypes using novel serotype-specific urinary antigen detection (SSUAD) assays (all serotypes in PCV15, PCV20, and V116 are included except 15B). Among the 242 serotypes detected by SSUAD assays, approximately 84% were covered by V116, compared to approximately 64% covered by PCV20. One-fourth (approximately 25%) of the detected serotypes were covered by V116 only and not by PCV15 or PCV20.
Additional Clinical Study Results Presented at ISPPD (Abstract #382 and #355) - Data from Phase 3 clinical studies STRIDE-4 (NCT05464420) and STRIDE-5 (NCT05526716) were also presented at ISPPD.
