FDA Approves Merck's 21-Valent Pneumococcal Vaccine for Adults 50 Years of Age and Older: A First and Long-Awaited

Merck announced approval by the US FDA of the company’s 21-valent pneumococcal conjugate vaccine Capvaxive formulated specifically for adults aged 50 and older and designed to cover serotypes responsible for approximately 84% of invasive pneumococcal disease in this population. 

The agency approval is based on phase 3 registration trials that demonstrated robust immune responses in both vaccine-naïve and vaccine-experienced adult populations, the company said.

The novel vaccine includes 8 unique serotypes that are not covered by currently FDA-approved pneumococcal vaccines, according to Merck. The 8 serotypes (15A, 15C, 16F, 23A, 23B, 24F, 31 and 35B) were responsible for approximately 27% of IPD cases in adult aged 50 years and older and approximately 31% in those aged 65 and older, according to data from the CDC.

Although there are no studies currently comparing the efficacy of Capvaxive and PCV20 ((pneumococcal 20-valent conjugate vaccine), the same CDC epidemiologic data from 2018-2021 show that the serotypes covered by Capvaxive cause more adult cases of IPD compared with serotypes covered by PCV20.

• In adults 50 years of age and older: covers the serotypes responsible for approximately 84% of IPD cases, compared to approximately 52% covered by PCV20.
• In adults 65 years of age and older: covers the serotypes responsible for approximately 85% of IPD cases, compared to approximately 51% covered by PCV20.

“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,” Dean Y Li, MD, PhD, president, Merck Research Laboratories, said in the company press release. “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.”

The approval of Capvaxive is backed by 4 phase 3 trials, including the phase 3 STRIDE-3 trial which evaluated the Merck vaccine against PCV20 in pneumococcal-naïve adults 18 years of age and older (N=2600). Capvaxive demonstrated statistically significant immune responses compared with PCV20 for serotypes common to both vaccines by geometric mean titer (GMT) of serotype-specific opsonophagocytic (OPA) activity 30 days post-vaccination with positive immune responses also recorded for the 8 serotypes unique to Capvaxive.

The phase 3 STRIDE-6 trial evaluated Capvaxive in adults aged 50 years and older (N=717) vaccinated against pneumococcus at least 1 year prior to the study with PPSV23, PCV13, and PCV15, alone or in combination. Capvaxive was immunogenic for all 21 pneumococcal serotypes in the vaccine. In the 2 investigational cohorts, OPA responses were higher for the serotypes unique to Capvaxive. For serotypes in common with Capvaxive, OPA responses were similar across the 3 cohorts who had previously received at least 1 pneumococcal vaccine. Primary end points included safety and geometric mean titer GMT of serotype-specific OPA responses 30 days post-vaccination.

The phase 3 STRIDE 5 trial evaluated Capvaxive when it was administered either concomitantly or sequentially (30 days later) with quadrivalent influenza vaccine (QIV) in the adult population aged 50 years and older. Capvaxive administered concomitantly with QIV was noninferior to the vaccine administered sequentially for 20 of the 21 serotypes and for 3 of the 4 influenza strains.

Even with the availability of current pneumococcal conjugate vaccines for adults, gaps in serotype coverage for invasive pneumococcal disease persist,” Eliav Barr, MD, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories said in a previous Merck statement.

An adult-specific pneumococcal vaccine has been elusive since the first marketed formulation against the infection in 1977 (polysaccharide), followed by the first conjugate vaccine in 2000. Both significantly reduced disease in both children and adults. Subsequent conjugate formulations with additional serotypes were increasingly more effective in children, but not in adults.

“What’s happened over time, because we have the ability to look at good surveillance data, what we’ve seen is that the serotypes causing disease in children are actually different than the ones causing disease in adults,” Heather Platt, MD, Merck’s pneumococcal vaccine lead, said in an interview with Fierce Pharma ahead of the approval.

The indication for the prevention of pneumonia is approved under accelerated approval based on immune responses as measured by OPA. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

The CDC's Advisory Committee on Immunization Practices is expected to meet on June 27 to discuss and make recommendations for the use of Capvaxive in adults.