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 H1 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 (54.4% in 2020) to the suboptimal coverage rates with MenB vaccines (28.4% of 17-year-olds received at least one MenB dose in 2020). However, this will depend on the strength of Advisory Committee on Immunization Practices (ACIP) recommendations. 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). Sanofi is also hoping countries will switch from monovalent serogroup C vaccines to MenQuadfi in toddlers, but the case for that is somewhat mixed.
• 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). However, GlaxoSmithKline filed in the US for a fully liquid version of Menveo in October 2021, which would eliminate that disadvantage. Within the five major European markets, where Menactra is not approved, Nimenrix dominates over Menveo, but the sales potential of the class has been 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. It launched in the US in Q1 2021 and entered Europe later in the year. For the US market, MenQuadfi has shown what appears to be superior immunogenicity on various serogroups versus Menveo, as a primary dose in adolescents, and versus Menactra, as a primary dose in adults and a booster dose in adolescents and adults, though there are some exceptions, and its label and publications do not clearly state the superiority. Still, with advantageous immunogenicity data in both of the key market segments for MenACWY vaccines, MenQuadfi is expected to erode the market shares of both US incumbents. However, a concerted marketing effort will be needed 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). For the European market, where Menactra is not approved, Sanofi is looking for MenQuadfi to broaden its reach. There is more competition due to Pfizer’s Nimenrix, but, as noted above, Sanofi is hoping MenQuadfi will overcome obstacles other quadrivalent vaccines have had in several countries, because they have not been able to show non-inferiority on MenC relative to monovalent vaccines in toddlers. In contrast, MenQuadfi has shown superiority over a MenC monovalent vaccine in that age group, which is hoped will clear the way for a switch to the quadrivalent vaccine, though given that concerns for other serogroups are greater in older individuals, the strength of the case may be somewhat mixed if MenQuadfi is priced higher. MenQuadfi also showed superiority on MenC versus Nimenrix, though the response rate was high for both and earlier studies did not suggest an advantage in other serogroups.
• 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 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 and limited coverage rates in adolescents are due to the low incidence of MenB IMD, as well as the limited durability of protection conveyed by the vaccines.
• 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 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 certain efficacy data was a factor in 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 limited activity in the meningococcal vaccines pipeline, with only four 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. GlaxoSmithKline also has an additional pentavalent candidate which it claims provides even broader strain coverage for infants and adolescents. Sanofi’s SP0230 is the company’s foray into MenB vaccines, which it claims has a broader strain coverage than current standards, and which it hopes to combine with MenQuadfi into a best-in-class pentavalent candidate. The final clinical-stage vaccine is a pentavalent vaccine being developed by the Serum Institute of India (MCV-5), which is targeting serogroup X in addition to ACWY for the Indian domestic market and other low-income countries.
• The overall likelihood of approval of a Phase I antibacterial, mycobacterial, or fungal asset is 18.6%, and the average probability an asset advances from Phase III is 61.0%. Antibacterial, mycobacterial, or fungal assets take 9.6 years on average from Phase I to approval, slightly longer than the 8.9 years in the overall infectious disease space.