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

• 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. A brief period of increased growth is expected with the anticipated launch of the 20-valent vaccine, PF-06482077, which may replace Prevnar 13 and Pneumovax 23 in adults (from June 2021) and Prevnar 13/V114 in infants (from mid-2023). Overall, the biggest opportunity for short-term growth within the pneumococcal vaccines market is associated with increasing vaccination rates within the elderly in the US and Italian markets; however, the 2019 reversal of the original 2014 ACIP recommendation for Prevnar 13’s use in the elderly population will hamper its growth in the US.
• As the only vaccine routinely recommended for use in infants in the US, Japan, and five major European markets (France, Germany, Italy, Spain, and the UK), 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 high price point has resulted in very limited uptake in the elderly outside of the US, as the more affordable Pneumovax 23 is generally recommended for the elderly population, with the exception of Italy, where both vaccines are recommended.
• 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 has 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.
• From June 2021, Prevnar 13’s market share in adults is expected to be cannibalized by Pfizer’s 20-valent successor vaccine, PF-06482077, which could potentially void the need for separate Prevnar 13 and Pneumovax 23 vaccinations. In a Phase III study, the 20-valent vaccine has demonstrated non-inferiority to the 13 strains shared with Prevnar 13, in addition to non-inferior immunogenicity for six out of the seven shared strains with Pneumovax 23, with one serotype (8) narrowly missing non-inferiority criteria. In addition, Prevnar 13 will also face competition in the infant segment for the first time from Merck & Co’s 15-valent V114, which has broader serotype coverage and is expected to gain approval in the pediatric setting in H1 2022 (approval in adults is expected in July 2021, but PF-06482077 is expected to be preferred due to broader serotype coverage). To protect the company’s market share in this lucrative segment, Pfizer is also investigating PF-06482077 in infants, and Datamonitor Healthcare expects US and EU indication expansions to be granted 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 T-cell-independent humoral responses. 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. Pneumovax 23 sales are expected to grow through to Q3 2021 due to the increasing elderly population in France, Spain, and the US. However, following PF-06482077’s anticipated approval from June 2021, Pneumovax 23’s sales could plummet if PF-06482077 gains recommendations for preferential use from national immunization advisory groups.
• 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.
• Presently, there are six vaccines in clinical development within the US, Japan, and five major European markets, with Merck & Co’s 15-valent V114 and Pfizer’s 20-valent PF-06482077 both currently under regulatory review by the FDA for the prevention of pneumococcal disease in adults. Both vaccines possess broader serotype coverage than the currently recommended Prevnar 13 and hope to benefit commercially from serotype shift in pneumococcal disease incidence.
• 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 8.6 years from Phase I to approval, compared to 9.0 years in the overall infectious disease space.