Disease Analysis: Meningococcal Vaccines

Definition

Meningococcal meningitis is caused by the bacteria Neisseria meningitidis, which causes a serious infection to the lining surrounding the brain and spinal cord. In all, 12 known serogroups of Neisseria meningitidis have been identified, six of which (A, B, C, W, X, and Y) can cause epidemics. The Centers for Disease Control and Prevention (CDC) has reported around 1 in 10 people are asymptomatic carriers of the bacteria.

Latest key takeaways

• The US meningococcal vaccines market is expected to grow over the forecast period due to incremental increases in MenACWY and MenB coverage rates in adolescents and young adults before the anticipated introduction of GlaxoSmithKline’s and Pfizer’s pentavalent vaccines in Q1 2024. Beyond this period, market growth will be driven by the uptake of pentavalent vaccines, which could significantly boost coverage for the MenB component by linking the higher coverage rates observed with the booster dose of MenACWY in adolescents (53.7% in 2019) to the suboptimal coverage rates with MenB vaccines (21.8% of 17-year-olds received at least one MenB dose in 2019). The pentavalent vaccines would also be more convenient for physicians and patients as they would reduce the total number of doses required during adolescence from four (two MenACWY + two MenB) to three.
• The five major European markets (France, Germany, Italy, Spain, and the UK) are expected to experience weak growth over the forecast period because pentavalent vaccines have much lesser appeal within the EU. Indeed, unlike the US market, none of the five major European markets routinely recommend both MenACWY and MenB vaccines in adolescents, meaning that the introduction of pentavalent vaccines would necessitate increased costs and add further complexity to immunization schedules, therefore the vaccines would be unlikely to be routinely reimbursed if approved. While new Spanish recommendations for routine use of MenACWY vaccines in adolescents aged 12 years and one-off catch-up vaccination for adolescents aged 13–18 years will drive a short-term increase in sales, weak growth in other markets will be dependent on incremental increases in vaccination coverage rates (primarily for Bexsero and MenACWY in Italy).
• Menactra currently dominates the lucrative MenACWY US market on account of its first-to-market status and more convenient presentation (ready-to-inject liquid) compared to Menveo (lyophilized MenA component that must be reconstituted with liquid MenCWY components before injection). Within the five major European markets, where Menactra is not approved, Nimenrix dominates over Menveo, but the sales potential of the class is limited as France and Germany restrict MenACWY reimbursement to niche groups considered at risk of invasive meningococcal disease (IMD).
• MenQuadfi is Sanofi’s successor vaccine to Menactra and will act to broaden the company’s target markets to include the EU following its anticipated EU launch in mid-2021 (approval occurred in November 2020). MenQuadfi has demonstrated superior immunogenicity for all four serogroups compared to Menveo when administered as a primary dose in adolescents aged 10–17 years, as well as superior immunogenicity compared to Menactra for serogroups A, C, and W-135 when administered as a booster dose in adolescents and adults. Thus, with compelling immunogenicity data in both of the key market segments for MenACWY vaccines, MenQuadfi is expected to erode the market shares of both incumbents. However, a concerted marketing effort will be required given physician inertia and the lack of data showing that the improved immune response translates into superior protection (such a trial would not be feasible due to the low incidence of IMD necessitating an impractically large sample size).
• Within the US, GlaxoSmithKline’s Bexsero competes against Pfizer’s Trumenba in individuals aged 10–25 years and has captured the majority of MenB market share because of its more convenient dosing schedule. Bexsero is recommended in a two-dose schedule where the doses only have to be separated by one month, while Trumenba must be administered in a two-dose schedule separated by six months (for adolescents aged 16–23 years), or in a three-dose schedule (at 0, 1, and 6 months) if patients are considered at high risk of IMD. The sales potential of both vaccines is limited by a relatively weak recommendation for use by the Advisory Committee on Immunization Practices (ACIP), which states that individuals aged 16–23 years “may” consider vaccination to gain short-term protection from infection as part of a shared clinical decision-making process between patients and physicians. This noncommittal recommendation is due to the low incidence of MenB IMD, as well as uncertainty over the magnitude and durability of protection conveyed by the vaccines, and has translated into suboptimal coverage rates in adolescents.
• GlaxoSmithKline hopes to increase Bexsero’s sales with a US indication expansion for use in infants, though an ongoing Phase III trial in this group is not expected to reach primary completion until July 2024. If approved for infants, positive real-world effectiveness data from the UK market could be presented to convince the ACIP to make a Category A recommendation for routine use of Bexsero (a lack of efficacy data was a key driver of the weaker Category B recommendation in adolescents), which would be very lucrative for GlaxoSmithKline as a multi-dose schedule is required and high coverage rates are typically achieved in infants.
• Unfavorable health technology assessment outcomes in France, Germany, and Spain have greatly limited the sales potential of MenB vaccines in the five major European markets, as these nations restrict their reimbursement to niche groups at risk of IMD. Italy and the UK are the only two of the five major European markets to routinely recommend infant MenB vaccination, and Bexsero monopolizes this lucrative niche as the only MenB vaccine approved for use in infants (Trumenba is only approved for individuals aged ≥10 years).
• There is very limited activity in the meningococcal vaccines pipeline, with only three candidates in clinical-stage development in the US, Japan, and five major European markets. GlaxoSmithKline and Pfizer are both developing pentavalent vaccines, MenABCWY and PF-06886992, respectively, which aim to partially or completely replace separate MenACWY and MenB vaccines for adolescents in the lucrative US market. Both vaccines could significantly boost the suboptimal coverage rates currently observed for MenB vaccines, which would drive substantial market growth, but their uptake will be heavily dependent on whether the ACIP is willing to upgrade its current weak recommendation for MenB vaccines in adolescents and young adults to a stronger Category A recommendation (which will require positive real-world effectiveness data for Bexsero/Trumenba). The final clinical-stage vaccine is a pentavalent vaccine being developed by the Serum Institute of India (MCV-5), but it is being targeted at the Indian domestic market and other low-income countries, thus is not expected to gain US approval.
• The overall likelihood of approval of a Phase I antibacterial, mycobacterial, or fungal asset is 18.9%, and the average probability an asset advances from Phase III is 60.4%. Antibacterial, mycobacterial, or fungal assets take 9.6 years on average from Phase I to approval, slightly longer than the 9.0 years in the overall infectious disease space.