Therapeutic focus – Novartis set to dominate meningitis vaccine market

Novartis today announced new information from pivotal studies of its meningitis B vaccine, 4CMenB, confirming protection against multiple strains of the disease. This data should be enough to win approval for the Swiss company's most valuable pipeline candidate, which would become the first vaccine to prevent meningitis B. 

Novartis is looking to build a broad franchise in meningitis and is preparing for year-end filings for two vaccines which, according to EvaluatePharma, have the potential to help double the size of the overall meningitis vaccine market to $3.3bn by 2016 (see table below). Approval will be sought for 4CMenB in Europe, and in the US for a broader label for Menveo in a crucial first-year infant population. This franchise is a major growth driver for Novartis, which has to win backing from regulators and national health agencies to ensure the vaccines live up to their blockbuster potential.

Meningococcal infection

Meningitis is an infection-induced inflammation of the meninges, protective membranes surrounding brain and central nervous system.

Bacterial infection is most serious. When normally harmless bacteria like Neisseria meningitides,responsible for meningococcal meningitis, cross a weakened blood-brain barrier the body elicits an inflammatory response. This increases swelling in the brain, which can cause brain damage or death. Symptoms are flu-like to start with, but patients can deteriorate severely within hours.

Different types of meningitis is brought on by several bacteria groups, including Haemophilus influenzae, and Streptococcus penumoniae. Furthermore, different strains and numerous subtypes of these bacteria can cause the disease. N. meningitides has five major subtypes, or serogroups – A, B, C, W135 and Y; the B serogroup has thousands of different strains.

Disrupted by routine

Immunisation programmes over the last three decades, providing protection against the range of causative infections, have caused cases to decrease significantly.

For example in the UK, introduction of the Haemophilus influenzae type B (Hib) vaccine in 1992, and meningitis C vaccine in 1999, led to near-eradication of these disease subtypes in the country.

Aventis’ Menomune was launched in 1999, the first vaccine against A, C, W135 and Y meningococcal serogroups. This was superseded by Sanofi-Aventis’ Menactra, approved for 11-55 year olds in 2005, and children from 2-10 years in 2007. Last year, these two products generated $736m in sales.

Novartis’ Menveo, approved this year, targets the same serogroups as Menactra (Novartis strengthens pipeline with positive regulatory decisions, February 22, 2010). Both are endorsed by the Centers for Disease Control and Prevention (CDC) as part of US adolescent vaccinations. Vaccination for children under 11 years old is only recommended for high-risk groups.

Plan B

A broad-coverage vaccine for meningitis B has so far proved elusive because there are thousands of strains.

However this represents the next big step for this disease, says Dr Paul Offit, Chief of Infectious Diseases at the Children’s Hospital of Philadelphia.

“Half the diseases for young [children] are caused by serogroup B,” he says.

Novartis’ 4CMenB is the most advanced candidate in this field. Pfizer has a similar vaccine which is expected to start phase III trials in a couple of months.

Dr Offit, who is a member of the Advisory Committee on Immunization Practices (ACIP) which recommends vaccines to the CDC for routine immunisation programmes, believes an effective vaccine could win backing. However, given the stage of trials and the low incidence of disease it is too early to tell whether these candidates will provide adequate efficacy data for the FDA, he says.

“It’s going to be hard [to prove efficacy] with meningococcal disease because it’s become relatively uncommon in the United States,” says Dr Offit.

The B strain accounts for 30% of US cases of meningitis, compared with 80% in Europe. The data Novartis announced today was from trials conducted in Europe and analysts believe the antibody data should be sufficient for European regulators. In the US, Novartis is conducting phase II trials, due to complete in late 2011, of the vaccine in different formulations. The FDA and Novartis have not yet finalised the clinical outcomes needed to be explored in phase III.

In phase III results for 4CMenB in 3,600 infants presented at the International Pathogenic Neisseria Conference (IPNC) in September, the vaccine met its primary endpoints: it induced immune responses against three strains, including 100% response rates in two of these cohorts, and also was acceptably tolerated when co-administered with routine childhood vaccinations.

Broad-spectrum data were released today from a different trial showing 4CMenB produced antibodies killing 85% of 124 geographically and genetically diverse strains of meningitis B in adults, and importantly 74% of 57 strains found in 2-12 month old infants.

Ensuring the kids are all right

A necessity for meningitis vaccines is safe paediatric use.

Approved for 11-55 year olds in February, the FDA is currently reviewing Menveo for meningitis A, C, W135, and Y in children from 2-10 years. A decision is expected by year-end, approval will put it on par with Sanofi's Menactra.

An approval in first-year infants, a particularly at-risk group, could be advantageous as Sanofi’s rival product does not have approval in children under two years.

Novartis will file in this setting in US this year, after recently reporting data in 4,500 infants from 2-12 months. Immune responses were seen in 94-100% of subjects, and Menveo was tolerated with other childhood vaccines, including importantly the pneumococcal vaccination Prevnar – pneumococcal infection can be another cause of meningitis, particularly in newborns.

Payer endorsement

For these vaccines, backing by national immunisation programmes will be key.

However, Dr Offit is unsure a young population for Menveo would receive full endorsement from health authorities.

Meanwhile the UK Department of Health has been advised to recommend young infant use only as a travel vaccine. There is little incidence of serogroups A, W135 and Y in the UK, and much older meningitis C vaccines have been successful for some time.

Winning payer backing for 4CMenB will be equally important.

Consensus at IPNC was that meningitis B vaccines would not be cost-effective for inclusion in routine infant vaccination schedules, according to analysts at Sanford C Bernstein. A UK model was used as an example, which assumed a 3-dose vaccine, at £40 per dose, with 75% effective coverage and 24-month long protection, equating to over £100,000 for every quality adjusted life year (Qaly). Cost-effectiveness would decrease further if recommended for a booster vaccination in adolescents. The UK's clinical effectiveness agency, Nice, currently sets a limit between £20,000-£30,000 per Qaly.

Nevertheless, for Novartis the franchise is worth $1.6bn in 2016 sales projections, a growth driver comparable with its two biggest oncology drugs Afinitor and Tasigna; Menveo, at $905m, is predicted to outsell rival Menactra at $533m.

According to EvaluatePharma data, Menactra sales are on a plateau, with a European filing yet to materialise despite Sanofi's intentions since 2005 to do so. The forecasts below suggest that Menveo’s approval will cap Menactra’s growth and take any new sales. 

Meanwhile, an approval and full endorsement for 4CMenB is seen as driving the overall market further.

Although 4CMenB is a projected $700m drug, uncertainty remains over whether waning disease numbers will work against the vaccine securing government endorsements. While a meningitis B vaccine might be scientifically important, it may not be the big commercial opportunity hoped for.

That said, analysts believe today’s broad coverage data in infants points to a European approval, where it would have a significant first-mover advantage; if approved, the extent to which health authorities’ endorse the vaccine will be the real indicator for success.

Worldwide meningitis vaccine market
WW annual sales ($m)
Product Pharmacological Class Company Status 2000 2002 2004 2006 2008 2010 2012 2014 2016
Menveo Meningococcal A, C, W-135 & Y vaccine Novartis Marketed - - - - - 170 476 719 905
4CMenB Meningococcal B vaccine Novartis Phase III - - - - - - 100 450 725
Menactra Meningococcal A, C, W-135 & Y vaccine Sanofi-Aventis Marketed - - - 304 594 554 532 534 533
Menhibrix/HibMenCY-TT Hib & meningococcal C & Y vaccine GlaxoSmithKline Filed - - - - - 27 219 315 396
NeisVac-C Meningococcal C vaccine Baxter International / ID Biomedical Marketed 55 66 120 79 141 158 174 192 210
Nimenrix Meningococcal A, C, W-135 & Y vaccine GlaxoSmithKline Phase III - - - - - - 23 124 181
Menomune Meningococcal A, C, W-135 & Y vaccine Sanofi-Aventis Marketed - 97 106 85 100 130 138 146 155
PF-5212366 (rLP2086) Meningococcal B vaccine Pfizer Phase II - - - - - - - 28 91
Other vaccines 338 145 28 48 152 208 181 138 121
Total meningitis vaccine market 393 308 254 516 987 1,248 1,843 2,645 3,317

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