Pivotal study published in JAMA confirms potential of Novartis(1) vaccine Bexsero™ to help protect infants against devastating meningococcal serogroup B disease

• Study including more than 1,800 infants showed Bexsero^™ induces an immune response in 79 per cent to 99 per cent when given alone or with other routine vaccines in different vaccination schedules².
• Current meningococcal vaccines do not provide protection against meningococcal B disease (MenB) which is easily misdiagnosed and can kill within 24 hours; infants are at highest risk³.
• MenB in Canada represents 82% of all meningococcal cases in infants below 1 year, 72% in children 1-4 years and 68% of all cases in adolescents.
• Health Canada is currently reviewing the first ever meningitis B vaccine for approval and use for Canadians.

DORVAL, QC, Feb. 9, 2012 /CNW/ - The Journal of the American Medical Association (JAMA) published a study today that shows Bexsero^™ induced a sufficient immune response against meningococcal B disease in the vast majority of infants vaccinated². In addition, these results show that Bexsero^™ can fit into various vaccination schedules in the first year of life when the likelihood of contracting this often-deadly disease is greatest. The study also demonstrated that Bexsero^™ has an acceptable tolerability profile.

These data were first presented in 2011 at the 29^th Annual Meeting of the European Society of Paediatric Infectious Diseases (ESPID)⁴.

"The publication of these results in JAMA adds to the growing body of evidence supporting Bexsero's potential to help protect all age groups, from infants to adults, against this devastating disease," said Andrin Oswald, Head of Novartis Vaccines and Diagnostics Division. "Bexsero holds great promise in providing a solution to a major public health concern - the lack of a routine vaccine providing broad protection against MenB."

In Canada, MenB causes 82 per cent (82%) of meningococcal meningitis cases in infants under 1 year of age and 68 per cent (68%) of the cases in adolescents⁵.

In general, approximately one in ten of people who contract meningococcal disease will die despite appropriate treatment^2,5,6. Of those surviving, around one in five suffers permanent disabilities such as brain damage, hearing loss, or learning difficulties^5,6. The majority of cases in some of the developed world are due to serogroup B (MenB)⁶, with a disproportionate disease burden in infants⁷. Meningococcal disease most commonly affects otherwise healthy persons, and in many cases physicians cannot diagnose and treat an infected child soon enough to avoid serious outcomes, therefore prevention through vaccination is a means to counter meningococcal disease.

"The development of a broadly protective vaccine against MenB disease has been a formidable challenge and, if successful, would represent an enormous step forward in the prevention of childhood meningitis," said Dr. Matthew Snape, Consultant in Vaccinology and General Paediatrics, University of Oxford, UK. "This study provides important data on how well infants' immune systems respond to this new MenB vaccine when given in a variety of schedules. This information is vital when considering how the vaccine could be incorporated into different immunization regimens around the world."

Study Design and Results
This pivotal Phase IIb open-label immunogenicity study¹ randomized 1,885 infants to receive Bexsero at 2, 4, 6 months together with routine infant vaccines; at 2, 4, 6 months with routine vaccines given separately at 3, 5, 7 months; or at 2, 3, 4 months together with routine infant vaccines. A control group received the routine vaccines only at 2, 3, 4 months. The routine vaccines used were 7-valent pneumococcal glycoconjugate vaccine and a combined diphtheria, tetanus, acellular pertussis, inactivated polio, hepatitis B and Haemophilus influenzae type b vaccine.

Immune response was measured using the human serum bactericidal antibody (hSBA) assay with a titer ≥ 1:5, which is the accepted level that correlates with protection. The study met all of its primary endpoints, and showed that the majority of infants vaccinated with Bexsero, at either dosing schedule with or without routine vaccines, achieved hSBA ≥ 1:5 against all vaccine antigens in tested MenB strains (H44/76, 5/99, NZ98/254). More than 99% of participants receiving Bexsero at 2, 4, 6 months (with or without routine vaccines) or at 2, 3 and 4 months (with routine vaccines) developed hSBA titers ≥ 1:5 against the reference strains 44/76 and 5/99. For NZ98/254 the ≥ 1:5 result was reached or exceeded in 79% (2, 4, 6 months with routine vaccines), 87% (2, 4, 6 months without routine vaccines) and 81% (2, 3, 4 months with routine vaccines) of patients on the corresponding schedules.

The immune response to routine vaccine antigens when co-administered with Bexsero was similar to that in the control group², except for slightly lower immune responses to pneumococcal serotype 6B and pertactin, comparable with other authorized vaccines. The data also showed that Bexsero, when administered alone, had a reactogenicity profile that was comparable to those of the routine vaccines². Fever, which is a common event following routine childhood immunizations, was observed more frequently in infants who received Bexsero together with routine infant vaccines compared to infants receiving routine vaccines alone². Fever was generally mild-to-moderate and of short duration, with more than 95% of cases resolving within 24-48 hours².

Bexsero is the result of more than 20 years of pioneering research in the fight to protect infants and other populations at risk of infection from MenB^8,9. To address the unpredictable and changing nature of meningococcus bacteria over time, Bexsero - comprising four key components that independently are highly immunogenic¹⁰ - was designed to protect against the majority of disease-causing strains worldwide. The immunogenicity and tolerability of Bexsero has been demonstrated in large Phase III clinical trials involving more than 8,000 infants, adolescents and adults with post-vaccination reactions comparable to those of other routine vaccines^11,12. In December 2010, a Marketing Authorization Application (MAA) for Bexsero was submitted in Europe and in other countries, including a proposed infant vaccination schedule consisting of three doses for the primary series. Regulatory action is expected later in 2012.

The study was published in the February 8, 2012 issue of JAMA² with the title of "Immunogenicity and tolerability of recombinant meningococcal serogroup B vaccine administered with or without routine infant vaccinations according to different immunization schedules: A randomized controlled trial" by Nicoletta Gossger MD, Matthew D Snape FRCPCH MD, et al.

About Bexsero
The Novartis Pharmaceuticals Canada Inc., Vaccines and Diagnostics' Bexsero vaccine (also known as 4CMenB) was developed using a pioneering approach known as "reverse vaccinology⁸." This was necessary because the approach used to produce a conjugate meningococcal vaccine against serogroups A, C, W-135 and Y could not be used for MenB. The capsular polysaccharide of MenB is identical to a polysaccharide component present in the human body and is therefore not immunogenic. In contrast to conventional methods of developing vaccines, reverse vaccinology was used to decode the genetic makeup (genome sequence) of MenB and select those proteins that were most likely to be broadly effective vaccine candidates⁸. Bexsero contains multiple components, which are highly immunogenic independently and, taken together, have the potential to protect against a broad range of disease-causing MenB strains¹⁰. To date, more than 8,000 infants, toddlers, and adults have been enrolled in studies of Bexsero^{1,13,14,15,16,17}. Bexsero is not currently authorized for use in any country, including Canada.  However, Health Canada is currently reviewing Bexsero, the first ever meningitis B vaccine for approval and use for Canadians.

Authorized vaccines are available to protect against meningococcal disease caused by serogroups A, C, W-135 and Y⁶; however, MenB remains an important unmet public health challenge⁶.

Disclaimer
The foregoing release contains forward-looking statements that can be identified by terminology such as "would," "could," "will," "promise," "potential," "proposal," or similar expressions, or by express or implied discussions regarding potential future marketing approvals for Bexsero or regarding potential future revenues from Bexsero. You should not place undue reliance on these statements. Such forward-looking statements reflect the current views of management regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results with Bexsero to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that Bexsero will be approved for sale in any market, or at any particular time. Nor can there be any guarantee that Bexsero will achieve any particular levels of revenue in the future. In particular, management's expectations regarding Bexsero could be affected by, among other things, unexpected regulatory actions or delays or government regulation generally; unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data; government, industry and general public pricing pressures; unexpected manufacturing issues; the company's ability to obtain or maintain patent or other proprietary intellectual property protection; competition in general; the impact that the foregoing factors could have on the values attributed to the Novartis Group's assets and liabilities as recorded in the Group's consolidated balance sheet, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

About Novartis Pharmaceuticals Canada Inc.
Novartis Pharmaceuticals Canada Inc. provides healthcare solutions that address the evolving needs of patients and societies. Focused solely on healthcare, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, cost-saving generic pharmaceuticals, preventive vaccines, diagnostic tools and consumer health products. Novartis is the only company with leading positions in these areas.  In 2010, the Company invested close to $100 million in research and development and conducted clinical trials across the country seeking new treatments in Ophthalmology, Respiratory diseases, Neurosciences (including MS), Immunology and Infectious diseases, Cardiovascular, Oncology (including Hematology) and organ transplantation. In addition to Novartis Pharmaceuticals Canada Inc., the Novartis Group consists of Novartis Animal Health Canada Inc., Novartis Consumer Health Canada Inc., Alcon Canada Inc. and Sandoz Canada Inc. For further information about Novartis Canada, please consult www.novartis.ca.

™Bexsero is a trademark.

References
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^{1 Novartis Pharmaceuticals Canada Inc., Vaccines and Diagnostics
2 Gossger N, et al. Immunogenicity and tolerability of recombinant meningococcal serogroup B vaccine administered with or without routine infant vaccinations according to different immunization schedules: A randomized controlled trial. JAMA 2012;307:573-82.
3 Thompson MJ, et al. Clinical recognition of meningococcal disease in children and adolescents. Lancet 2006;367:397-403.
4 Gossger N, et al. Immunogenicity of an investigational multicomponent meningococcal serogroup B vaccine (4CMenB) administered with or without routine infant vaccinations in different schedules. Presented at 29th ESPID Meeting, June 7-10, 2011; The Hague, The Netherlands. Poster #1205.
5 Health Protection Agency. Infectious Diseases: Meningococcal disease. Meningococcal Reference Unit isolates of Neisseria Menengitidis: England and Wales, by serogroup & epidemiological year, 1998/99-2008/09. Available and Canadian Communicable Disease Report (CCDR), April 2009, Volume 36, ACS-3
6 Perrett KP, Pollard AJ. Towards an improved serogroup B Neisseria meningitidis vaccine. Expert Opin Biol Ther 2005;5:1611-25.
7 Centers for Disease Control and Prevention. Meningitis: Signs and Symptoms. June 2009. Available at: http://www.cdc.gov/meningitis/about/symptoms.html. Last accessed on 9 Jan 2012.
8 Rappuoli R. Reverse vaccinology, a genome-based approach to vaccine development. Vaccine 2001;19:2688-91.
9 Giuliani MM, et al. A universal vaccine for serogroup B meningococcus. Proc Natl Acad Sci USA 2006;103:10834-9.
10 Donnelly, J et al. Qualitative and quantitative assessment of meningococcal antigens to evaluate the potential strain coverage of protein-based vaccines. Proc Natl Acad Sci USA 2010;107:19490-5.
11 Beeretz, I et al. Reactogenicity and Safety of Multicomponent Meningococcal Serogroup B Vaccine (4CMenB) Administered With or Without Routine Infant Vaccinations in Different Schedules, presented at the 29th European Society for Paediatric Infectious Diseases Conference, June 7-11, 2011, The Hague, The Netherlands
12 Esposito S, et al. Tolerability of a three-dose schedule of an investigational, multicomponent, meningococcal serogroup B vaccine and routine infant vaccines in a lot consistency trial. Presented at IPNC, Sept 11-16, 2010. Banff, Canada. Poster #182.
13 Santolaya ME, et al. Immunogenicity and tolerability of a multicomponent meningococcal serogroup B (4CMenB) vaccine in healthy adolescents in Chile. Lancet 2012 Jan 17. [ePub ahead of print].
14 Findlow J, et al. Multicenter, open-label, randomized phase II controlled trial of an investigational recombinant meningococcal serogroup B vaccine with and without outer membrane vesicles, administered in infancy. Clin Infect Dis 2010;51:1127-37.
15 Snape MD, et al. Immunogenicity of two investigational serogroup B meningococcal vaccines in the first year of life: a randomized comparative trial. Pediatr Infect Dis J 2010;29:e71-9.
16 Prymula R, et al. Catch-up vaccination of healthy toddlers with an investigational multicomponent meningococcal serogroup B vaccine (4CMenB) - exploration of a two-dose schedule. Presented at 29th ESPID Meeting, June 7-11, 2011; The Hague, The Netherlands. Poster #706.
17 Vesikari T, et al. Immunogenicity of an investigational, multicomponent, meningococcal serogroup b vaccine in healthy infants at 2, 4, and 6 months of age. Presented at IPNC, Sept 11-16, 2010; Banff, Canada. Poster #180.}

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