Disease Analysis: Pneumococcal Vaccines

Disease Overview

Streptococcus pneumoniae (S. pneumoniae) is a bacterium that can cause multiple types of pneumococcal disease, including bloodstream infections (sepsis), pneumonia, meningitis, and other milder diseases such as sinusitis and otitis media. The severity of pneumococcal disease is characterized as invasive or non-invasive, with invasive pneumococcal disease being more severe as the bacterium can be isolated from ordinarily sterile sites (eg blood or cerebrospinal fluid), and requires hospital treatment.

Latest key takeaways

• Streptococcus pneumoniae (S. pneumoniae) is a bacterium that can cause multiple types of pneumococcal disease including bloodstream infections (sepsis), pneumonia, meningitis, and other milder diseases such as sinusitis and otitis media. According to the World Health Organization (WHO), there are 90 distinct pneumococcal serotypes identified, with 23 serotypes accounting for 90% of invasive pneumococcal infection in industrialized countries. According to the WHO, 1.6 million deaths were caused by pneumococcal infection in 2005, including between 700,000 and 1 million deaths in children aged under five years.
• The value of the pneumococcal vaccines market will steadily grow over the forecast period due to increasing elderly populations across France, Spain, and the US, alongside continued short-term price increases in the lucrative US market. Overall, the biggest opportunity for short-term growth within the pneumococcal vaccines market is associated with increasing vaccination rates in the elderly in the US and Italian markets, and in 2021 a brief period of increased growth followed the launch of Merck & Co’s Vaxneuvance (15-valent pneumococcal conjugate vaccine; PCV15) and Pfizer’s Prevnar 20 (20-valent pneumococcal conjugate vaccine; PCV20).
• Prevnar 20, the successor to Pfizer’s blockbuster Prevnar 13 (13-valent pneumococcal conjugate vaccine), and Vaxneuvance were approved back-to-back by the FDA in June 2021 and July 2021, respectively. Since then, Prevnar 13’s market share has been cannibalized to an extent as both vaccines are now recommended by the Advisory Committee on Immunization Practices (ACIP) at parity, superseding recommendations for Prevnar 13 in elderly populations in the US, with a sequential dose of Merck’s Pneumovax 23 (23-valent pneumococcal polysaccharide vaccine) being required when Vaxneuvance is used. European approval has also been granted to both Vaxneuvance and Prevnar 20 (as Apexxnar) for use in adults, but guidelines in the five major European markets (France, Germany, Italy, Spain, and the UK) are yet to be updated to include recommendations for either.
• As the only vaccine routinely recommended for use in infants in the US, Japan, and five major European markets, Prevnar 13 generates blockbuster revenues from this segment on account of large annual birth cohorts, high vaccination coverage rates, and its multi-dose schedule (2–4 doses are recommended depending on the market). However, Prevnar 13’s market share could soon start to be eroded in the infant segment, where Pfizer and Merck are in a race towards approval in pediatric populations.
• Vaxneuvance was expected to be approved for infants and children in H1 2022, but a three-month extension was unexpectedly added to the original PDUFA date set by the FDA. The PDUFA date is now set for 1 July 2022, meaning Vaxneuvance will have less time to gain market share before Prevnar 20 is potentially approved in mid-2023. As a pneumococcal polysaccharide vaccine, Pneumovax 23 is not recommended for routine use in infants as it does not stimulate protective immunity in this age range, which is thought to be due to the inability of individuals aged <24 months to mount humoral responses that are independent of T cells. The lack of an independent humoral response has resulted in Pneumovax 23’s use being limited to the elderly, where its broad serotype coverage is attractive.
• Strong adherence to immunization guidelines has resulted in high infant pneumococcal vaccination rates across the US, Japan, and five major European markets. However, key opinion leaders have stated that there is a significant unmet need to increase vaccination coverage rates in the “at-risk” populations, which are currently limited by lack of awareness of vaccination recommendations and patient eligibility among primary care physicians and patients. In addition, adolescents and younger adults tend to have less frequent contact with physicians than infants and the elderly, which limits opportunities to refer patients for vaccination.
• The changing epidemiology of pneumococcal disease has influenced vaccine and dosing recommendations in the US and UK. In 2019, the US ACIP updated its vaccination guidance to remove its previous 2014 recommendation for the routine administration of a single dose of Prevnar 13 for all adults aged ≥65 years. This change in stance was because the use of Prevnar 13 caused a decline in invasive pneumococcal disease (IPD) incidence among adults and children (due to both direct and indirect herd protection effects), thus reducing the socioeconomic rationale for the vaccine’s routine use in the elderly. Indeed, since the initial 2014 recommendation for Prevnar 13’s use in the elderly, the incidence of IPD in the elderly has remained unchanged at five per 100,000 individuals, implying no clear population benefit of the previous recommendation. Additionally, within the UK, Public Health England has reduced the number of recommended doses of Prevnar 13 in infants from three to two based on the very low incidence of IPD caused by the 13 serotypes included in the vaccine and the low carriage of the serotypes in the general population. While the decision was not directly motivated by cost savings in the UK, it could serve as a model for other markets with low IPD incidence, as well as low-income markets where the high cost of Prevnar 13 acts as a major hurdle for the implementation of national vaccination programs.
• Presently, there are five vaccines in clinical development within the US, Japan, and five major European markets, with Phase III pivotal studies being prepared for Affinivax/Astellas’s novel 24-valent pneumococcal vaccine, ASP3772, following positive Phase II results showing the candidate is immunogenic and well tolerated.
• The overall likelihood of approval of a Phase I pneumococcal vaccine is 16.7%, and the average probability a vaccine advances from Phase III is 75%. Pneumococcal vaccines, on average, take 8.4 years from Phase I to approval, compared to 8.9 years in the overall infectious disease space.