Novartis Phase III Study Shows Meningococcal B Vaccine Candidate Could Be First To Provide Broad Coverage Against Deadly Disease

Novartis Phase III Study Shows Meningococcal B Vaccine Candidate Could Be First To Provide Broad Coverage Against Deadly Disease

New data presented by Novartis Vaccines involving thousands of babies indicates that an investigational vaccine has the potential to be the first broad-coverage vaccine against the deadly meningococcal B (meningitis B) disease. 1

There is currently no broad-protection vaccine available against meningitis B, although vaccines exist against other strains.

The findings were released at the International Pathogenic Neisseria Conference (IPNC) in Banff, Canada.

The Phase III trial looked at a Multicomponent Meningococcal Serogroup B Vaccine (4CMenB). The study involved more than 3,600 infants from five European countries - Austria, Czech Republic, Finland, Germany and Italy.

Results show that the large majority of those vaccinated with 4CMenB at the same time as other routine vaccines achieved a robust immune response against all the vaccine's meningitis B antigens.1 (Antigens are components of bacteria or viruses used in vaccines to stimulate the immune system so it recognises later when the real threat is encountered.)

Additionally, results show that 4CMenB had an acceptable tolerability profile when administered with other routine infant vaccines,2 which supports potential use of the vaccine in the first year of life, when the medical need is greatest. 3

Andrin Oswald, Head of Novartis Vaccines and Diagnostics Division, said: "The challenge with meningitis B is that there are thousands of circulating strains and developing a broadly protective vaccine has, until now, been difficult."

He added: "These critical data highlight the promise of our innovative candidate 4CMenB vaccine in addressing the unmet public health need of meningitis B, the most common cause of bacterial meningitis for which there is no readily available global vaccine." 4

Two years ago, on 14 May 2008, Novartis Vaccines released the first data showing the potential promise of the vaccine in a study involving 150 British infants. 5

Professor Andrew Pollard, head of the Oxford Vaccine Group at the University of Oxford, who helped run the British study, welcomed the latest news from the larger trial.

"Meningitis B can be devastating for affected families and is a major concern for paediatricians who care for children with this serious illness. The disease can strike healthy children without warning and, in some countries, is the leading infectious cause of death in early life," he said.

Professor Pollard added: "Many cases of meningitis are prevented today by the vaccines we give to our children but the more complex meningitis B remains as a major threat to public health. The encouraging data presented on 4CMenB indicate the potential for additional protection to be provided by this new vaccine."

Across the UK there are in excess of 1,200 cases of meningitis B each year, resulting in some 120 deaths and around 250 children left with serious life-long complications such as limb amputations, blindness, deafness and brain damage.

Notes

About meningitis disease in the UK

Figures from the Health Protection Agency for England and Wales in the financial year 2008/2009 show a total of 1,052 cases of meningitis B. 6

The largest single group to be affected by age range were babies under one year old - with 284 cases. The next largest group occurred in babies between one year and two years old with 139 cases. Cases peaked again at ages 15 to 19 years, with 111 cases. Amongst people over 25 there were 163 cases. 6

The HPA does not collect deaths from meningitis B, but says the disease carries a case fatality rate of 10% which implies around 100 deaths a year in England and Wales. 7

Aside from deaths a proportion of survivors - around 20% or one in five - will suffer serious and lifelong consequences such as limb amputation, blindness, deafness and brain damage. 8

Figures from Health Protection Scotland show that in Scotland there are around 150 cases of meningitis notified each year, of which some 75% are meningitis B which implies around 112 cases. Of these meningitis B cases, 60% occur in the under-five age group. 9

In Northern Ireland in the financial year 2005/06 there were 57 cases of meningitis B. 10

Widespread vaccination against meningitis C was introduced across the UK in 2000, with everyone up to age 24 being offered the vaccine, with a result that cases from that strain have virtually disappeared in this country. 11

Around 92% of babies are now routinely vaccinated against meningitis C. 12

In the financial year 2008/2009 there were just 13 cases of meningitis C across England and Wales, of which nine occurred in people over 25. In the year 1998/1999, before vaccination was introduced, there were 955 cases in England and Wales. 13

Across England and Wales in 2008/2009 there were 58 cases of meningitis Y and 21 of meningitis W-135. 14

About the vaccine

The Novartis 4CMenB vaccine was developed using a pioneering approach known as "reverse vaccinology." In contrast to conventional methods of producing vaccines, reverse vaccinology decodes the genetic makeup of MenB and finds the specific components that most typically cause infection.15

4CMenB Clinical Trial Results Presented at IPNC

Results from the clinical Phase III trial show that a majority of infants vaccinated with 4CMenB concomitantly with other routine vaccines achieved a robust immune response against the three vaccine MenB antigens.

The vaccine was administered at 2, 4, and 6 months of age.1, 2 One month after the third 4CMenB dose, the percentage of subjects achieving serum bactericidal antibodies using human complement (hSBA) ≥1:5 against three MenB strains (5/99, NZ98/254 and H44/76) were 100 percent, 84 percent and 100 percent, respectively.1

All three lots of investigational 4CMenB showed highly consistent immune responses. 1 In addition, responses to routine infant vaccine antigens when co-administered with 4CMenB were similar with the exception of a slightly diminished polio 2 response when compared to routine vaccine administration alone. 1

4CMenB also had an acceptable tolerability profile when co-administered with other routine infant vaccines. 2 Typical vaccine associated events solicited for 7 days after each vaccination showed a similar incidence (83 percent after routine vaccine alone compared to 87 percent following routine vaccine co-administered with 4CMenB). 2

The events were similar in nature and quality (mostly injection site reactions and systemic reactions such as sleepiness, changed eating habits, irritability, unusual crying and rash, or gastrointestinal events).2 Events in both groups were mostly mild or moderate reactions and transient, following a typical pattern of routine vaccinations. 2

Fever, which is a common event following routine childhood immunizations, was observed more frequently in infants who received the 4CMenB vaccine together with routine infant vaccines compared to infants receiving routine vaccines alone. 2 Fever was generally low-grade, mild and of short duration, with 95 percent of cases resolving within 24-48 hours. 2 These preliminary data findings will complement additional safety data that Novartis is evaluating as part of its complete phase III programme.

Incidence of serious adverse events in infants who received 4CMenB with routine vaccines was comparable to those who received routine infant vaccines alone and those who received meningococcal C conjugate vaccine with routine infant vaccines. 2 In the study, less than one percent of infants discontinued the trial due to reactogenicity following vaccination with no difference between groups. 2

Trial Design

This Phase III, randomized, controlled, multi-center study involved 3,630 healthy infants in trial sites throughout Europe. The primary endpoints of the study were to determine the consistency of immune response to three lots of 4CMenB, and assess the immunogenicity and tolerability of three doses of 4CMenB (three lots combined) given concomitantly with routine infant vaccines.

The trial included an open-label immunogenicity and tolerability subset in which participants were randomized to receive one of three lots of 4CMenB vaccine with routine infant vaccines, or routine vaccines alone.

Also included was an observer-blind safety subset in which participants were randomized to receive 4CMenB vaccine or meningococcal C conjugate vaccine with routine vaccines, or routine vaccines alone. Immunizations were administered at 2, 4, and 6 months of age.

Primary immunogenicity was based on a serum bactericidal assay using human complement (hSBA) against three serogroup B strains (5/99, NZ98/254 and H44/76) 30 days after the final study vaccination. Injection site and systemic reactions were recorded for seven days post-vaccination, and adverse events were evaluated throughout the study. 1,2

About the 4CMenB Clinical Programme

The entire 4CMenB Clinical program consists of clinical trials studying the immunogenicity, safety and tolerability of the investigational vaccine in four major age groups, including infants, toddlers, adolescents and adults worldwide. Results from a Phase II study in adults showed that 4CMenB generated an immune response and was generally well tolerated. 16

Remaining Phase III trial results are expected later this year. The comprehensive data of more than 7,500 subjects is expected to be the basis for the planned filing in the EU by year end.

In addition, studies are under way to confirm the expected coverage of the broad-based vaccine against MenB strains circulating in several countries. The first results are expected prior to filing.

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