A new vaccine, designed to prevent a form of meningococcal disease, is closer to expanded use after Pfizer announced positive Phase III results in August. The latest trial results for Trumenba, which guards against meningococcal serogroup B (MenB), were in keeping with results from previous Phase II studies. Positive data was drawn from two independently controlled and randomised Phase III trials conducted in Europe and the US.Close to 7,000 healthy patients aged 10-25 participated in the trials as Trumenba’s safety and immunogenicity were evaluated. One month after the final dose of Trumenba was administered, immunogenicity was determined on the back of a bactericidal assayusing human complement. Experts believe the results for Trumenba could thrust Pfizer to a prime position in the emerging US MenB vaccine market, potentially staving off competition from only rival, GlaxoSmithKline’s vaccine, Bexsero.

While infants up to 12 months of age are most susceptible to the life-threatening disease, MenB also afflicts adolescents aged 10-25. Vaccines for four of the five serogroups (MenA, C, W, and Y) have been licensed on the market for years and are staples in adolescent vaccination schedules across the US. However, a vaccine against serogroup B, caused by the Gram-negative bacterium, Neisseria meningitides, had been elusive until 2014. Now the FDA has approvedboth Trumenba and Bexsero for use in adolescents and adults aged 10-25.

Pfizer’s announcement of promising data for Trumenba comes on the heels of the Center for Disease Control and Prevention’s (CDC’s) June 2015 recommendation to have physicians decide whether to administer a MenB vaccination on a case-by-case basis, which was made in response to multiple outbreaks of MenB on college campuses in the US (California, New Jersey, Rhode Island, and Oregon). Key opinion leaders (KOLs) interviewed by GlobalData concurred that a MenB vaccine represents the greatest unmet need in the toolkit against MenB disease, so the expedited approvals of Trumenba and Bexsero are welcome additions to the treatment landscape.

Pharmaceutical companies have struggled mightily over the last two decades to develop a vaccine specifically against the B serogroup. In contrast with the MenACWY vaccines, which elicit a host immune response by leveraging conjugated polysaccharides purified from the bacterial outer membrane, Pfizer had to find an alternative to this approach for the MenB vaccine, as the MenB polysaccharides exhibit a high similarity to human polysialic acid. Trumenba contains two variants of recombinant lipoprotein 2086 (rLP2086) as its antigenic components, with one of the two variants found on the outer membrane of over 97% of MenB strains. Bexsero consists of four different antigenic components: Neisseria heparin-binding antigen, neisserialadhesin A, factor H binding protein, and outer membrane vesicles containing Porin A, which are all located on the outer membrane of most MenB strains. Though distinct, both vaccine design approaches showed enough promise to merit US licensure, which was contingent upon the generation of additional clinical data. Therefore, GlobalData expects the quality and quantity of post-marketing data being generated for these two MenB vaccines — with added emphasis on appropriate trial design and targeted patient populations — to be the key differentiator in their future commercial positioning.

Limited by an already crowded infant vaccination schedule in the US, and reluctance on the patient side towards additional vaccines, Pfizer has positioned Trumenba in the US market not only by aligning it with the high prevalence of MenB in adolescents, but also with the possibility of combining Trumenba with an existing set of vaccines on the adolescent schedule (MenACWY, human papillomavirus [HPV], tetanus, diphtheria, and pertussis [Tdap]). In contrast to Europe, the US has a strong history of favoring the immunization of adolescents against meningitis, further adding to the appeal of this commercialization approach. Towards this goal, Pfizer announced the successful completion of a Phase II trial earlier this year in which Trumenba was administered concomitantly with MenACWY and Tdap in adolescents. The most recent results validate this commercial strategy, as Pfizer is now in a commanding position in the US MenB vaccine marketplace, particularly if the post-marketing data generated for Trumenba lead to its future inclusion in the routine adolescent immunization schedule.

Despite its recent success, Pfizer faces multiple challenges regarding Trumenba’s widespread uptake in the US. Due to the low incidence rate of MenB, efficacy studies are limited to the use of indirect assays and surrogate endpoints, thereby increasing the difficulty of demonstrating efficacy in the general population as well as superiority over competing vaccines. Furthermore, Trumenba’s duration of protection must be further investigated, as a study published by Prof. Andrew J. Pollard of the University of Oxford’s Department of Paediatrics, and Director of the Oxford Vaccine Group, in April, 2015 in the Canadian Medical Association Journal reported a significant loss of immunity in children after immunization with Bexsero. Additional studies should also determine a possible correlation between immunization against MenB and the carriage of MenB strains in the population, with the goal of demonstrating a possible herd-immunity effect as a supportive argument to add Trumenba to the routine adolescent vaccination schedule.

In conclusion, GlobalData believes that the preliminary data from these two Phase III trials are a major step towards demonstrating the safety and efficacy of Trumenba in the MenB-vulnerable age group, and have put Pfizer in an advantageous position in the US vaccination market. Also, if additional future trials can demonstrate that Trumenba results in prolonged immunogenicity and carriage inhibition, GlobalData anticipates that Pfizer might soon see its MenB vaccine being incorporated into the routine vaccination schedule for adolescents in the US.

 

*This article first appeared on GlobalData on 27 August 2015