Merck, also known as MSD, revealed that the U.S. Food and Drug Administration (FDA) has authorised VAXNEUVANCE™ (Pneumococcal 15-valent Conjugate Vaccine) (pronounced VAKS-noo-vans) for the active immunization of adults 18 years and older to prevent invasive pneumococcal disease caused by Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F.
Merck’s application was granted priority review by the FDA, which resulted in the approval. It is exempt for Individuals who have had a severe allergic response (e.g., anaphylaxis) to any component of VAXNEUVANCE or to diphtheria toxoid who are strongly advised not to take it, as indicated on Select Safety Information.
The U.S. Centers for Disease Control and Prevention’s (CDC) Advisory Committee on Immunization Practices (ACIP) is expected to meet in October to discuss and make recommendations on the use of VAXNEUVANCE in adults.
On Friday Merck tweeted:
VAXNEUVANCE Elicited Superior Immune Responses
VAXNEUVANCE’s authorization is founded on the clinical data of seven randomized, double-blind clinical trials, which analysed its tolerability, and immunogenicity. Moreover, according to the opsonophagocytic activity (OPA) Geometric Mean Titers (GMTs) evaluation, the immune responses induced by VAXNEUVANCE were non-inferior to the presently available 13-valent pneumococcal conjugate vaccine (PCV13) for the 13 common serotypes. Furthermore, they were superior to PCV13 for shared serotype 3 and for the two serotypes unique to VAXNEUVANCE, 22F and 33F.
In the pivotal Phase 3 PNEU-AGE (V114-019) study, superiority for VAXNEUVANCE relative to PCV13 was based on statistically significantly greater OPA GMT ratios for serotypes 22F [GMT Ratio 32.52 (95% Confidence Interval (CI) 25.87, 40.88)] and 33F [GMT Ratio 7.19 (95% CI 6.13, 8.43)], as well as of the key secondary objective assessing serotype 3 [GMT Ratio 1.62 (95% CI 1.40, 1.87)]. Randomized controlled trials assessing the clinical efficacy of VAXNEUVANCE compared to PCV13 have not been conducted.
Dr. Jose Cardona, Indago Research and Health Center, coordinating investigator for the PNEU-AGE trial, stated:
“Some adults, including older adults or those with certain chronic medical conditions or immunocompromising conditions, are at increased risk for pneumococcal disease and its serious, sometimes life-threatening complications. The FDA’s approval of VAXNEUVANCE is based on robust Phase 2 and 3 studies assessing immune responses in a broad range of adult populations and provides an important new option in protection from invasive pneumococcal disease.”
Invasive pneumococcal disease (IPD)
Pneumococcal disease is an infection caused by bacteria called Streptococcus pneumoniae, or pneumococcus. Different strains of this bacteria are called serotypes. Invasive pneumococcal disease (IPD) occurs when the bacteria infect parts of the body that are usually free from germs. Adults 50 years and older account for approximately 80% of all adult IPD burden. Serotypes 3, 22F, and 33F play a substantial role in the burden of IPD, and serotype 3 being the most common cause of IPD in adults in the United States.
Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories stated:
“At Merck, we are committed to helping protect more people from invasive pneumococcal disease. That’s why we set out to develop a conjugate vaccine that includes pneumococcal serotypes that pose the greatest threat and elicits a strong immune response to each serotype covered. The FDA approval of VAXNEUVANCE builds on Merck’s more than 40 years of experience in pneumococcal disease prevention with a new option that includes serotypes responsible for substantial disease burden in adults, like serotype 3, as well as serotypes 22F and 33F, which are associated with a high degree of invasiveness and antibiotic resistance.”
VAXNEUVANCE is a 15-valent pneumococcal conjugate vaccine developed by Merck. It comprises of isolated capsular polysaccharides from S. pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F, each coupled to CRM197 carrier protein. VAXNEUVANCE is recommended for active immunization against invasive disease caused by S. pneumoniae serotypes found in the vaccine. The FDA previously designated VAXNEUVANCE as a Breakthrough Therapy for the prevention of IPD in individuals 18 years and older. The vaccine was given Priority Review status in January 2021.
In the United States and also many international jurisdictions, Merck is contesting the validity of several Pfizer Inc. patents related to pneumococcal vaccination technology.
Clinical Data Supporting the FDA Approval of VAXNEUVANCE
VAXNEUVANCE has been approved based on data from seven randomized, double-blind clinical studies designed to evaluate its safety, tolerability, and immunogenicity in 7,438 individuals from a variety of adult populations and clinical circumstances, 5,630 of whom received VAXNEUVANCE.
These included studies of healthy adults 50 years of age and older. The pivotal Phase 3 active comparator-controlled study assessed serotype-specific OPA responses for each of the 15 serotypes contained in VAXNEUVANCE at 30 days post-vaccination in pneumococcal vaccine naïve participants randomized to receive either VAXNEUVANCE (n=604) or PCV13 (n=601) (V114-019/PNEU-AGE [NCT03950622]). The study demonstrated that VAXNEUVANCE was non-inferior to PCV13 for the 13 shared serotypes and induces statistically significantly greater OPA GMTs compared to PCV13 for shared serotype 3 and for the two unique serotypes (22F, 33F).
The studies also included adults 18-49 years of age with no history of pneumococcal vaccination, including individuals at increased risk of developing pneumococcal disease. A Phase 3 descriptive study included individuals with stable underlying medical conditions (e.g., diabetes mellitus, renal disorders, chronic heart disease, chronic liver disease, chronic lung disease including asthma) and/or behavioral risk factors (e.g., smoking, increased alcohol use) that increased their risk of developing pneumococcal disease. Participants were randomized to receive VAXNEUVANCE (n=1,135) or PCV13 (n=380), followed by PNEUMOVAX® 23 (pneumococcal vaccine polyvalent) six months later (V114-017/PNEU-DAY [NCT03547167]). VAXNEUVANCE elicited immune responses to all 15 serotypes as assessed by OPA GMTs at 30 days following vaccination. Additionally, following vaccination with PNEUMOVAX 23, the OPA GMTs for the 15 serotypes in VAXNEUVANCE were numerically similar among subjects who had received VAXNEUVANCE or PCV13 for the first vaccination.
Further, the studies have included adults living with HIV, an immunocompromising condition. A Phase 3 descriptive study assessed the use of VAXNEUVANCE in pneumococcal vaccine naïve HIV-infected adults 18 years of age and older with CD4+ T cell count ≥50 cells per microliter and plasma HIV RNA value <50,000 copies/mL (V114-018/PNEU- WAY [NCT03480802]). Participants were randomized to receive VAXNEUVANCE (n=152) or PCV13 (n=150), followed by PNEUMOVAX 23 two months later. OPA GMTs were higher after administration of VAXNEUVANCE, compared to pre-vaccination, for the 15 serotypes contained in VAXNEUVANCE. After sequential administration with PNEUMOVAX 23, OPA GMTs were numerically similar between the two vaccination groups for all 15 serotypes contained in VAXNEUVANCE.
Co-administration of VAXNEUVANCE with seasonal quadrivalent influenza vaccine (QIV). A Phase 3 trial evaluated adults 50 years of age and older who were randomized to receive VAXNEUVANCE concomitantly with a seasonal inactivated QIV (Fluarix Quadrivalent) (n=600) or non-concomitantly 30 days after QIV (n=600) (V114-021/PNEU-FLU [NCT03615482]). The non-inferiority criteria for the comparisons of GMTs were met for the 15 pneumococcal serotypes in VAXNEUVANCE and for the 4 influenza vaccine strains tested. VAXNEUVANCE can be administered concomitantly with a seasonal inactivated influenza vaccine.
In addition, it included the use of VAXNEUVANCE as part of a sequential regimen with PNEUMOVAX 23.
A Phase 3 active comparator-controlled descriptive study in pneumococcal vaccine-naïve adults 50 years of age or older assessed the use of VAXNEUVANCE (n=327) or PCV13 (n=325), followed by PNEUMOVAX 23 one year later (V114-016/PNEU-PATH [NCT03480763]). Following vaccination with PNEUMOVAX 23, OPA GMTs were numerically similar between the two vaccination groups for the 15 serotypes in VAXNEUVANCE.
For more than a century, Merck, known as MSD outside of the United States and Canada, has been inventing for life, bringing forward medicines and vaccines for many of the world’s most challenging diseases to save and improve lives. The company has demonstrated its commitment to patients and population health by increasing access to health care through far-reaching policies, programs and partnerships. Today, Merck continues to be at the forefront of R&D to prevent and treat diseases that threaten people and animals – including cancer, infectious diseases such as HIV and Ebola, and emerging animal diseases – as we aspire to be the premier research-intensive biopharmaceutical company in the world.
For more information, visit www.merck.com