[The FDA issued a CRL for Menveo in Jul 2009 citing CMC issues (#msg-39188485); NVS replied to the CRL one month later, and an FDA decision is expected in early 2010. Please see actual PR for footnote references.]
›Novartis meningococcal vaccine Menveo® recommended for approval in the European Union for prevention of disease in adolescents and adults
• Investigational vaccine Menveo demonstrates a protective immune response in four of the five major bacteria groups responsible for meningococcal disease
• Meningococcal disease is a major cause of bacterial meningitis and sepsis with high consequent disability and mortality rates worldwide
Basel, December 18, 2009 – Novartis Vaccines announced today that Menveo® (Meningococcal Group A, C, W-135 and Y-CRM Conjugate Vaccine) has received a Positive Opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMEA). The investigational conjugate vaccine is recommended for active immunization of adolescents (from 11 years of age) and adults at risk of exposure to Neisseria meningitidis groups A, C, W135 and Y, to prevent invasive disease. Menveo is designed to help protect against four of the five major groups of meningococcal bacteria, which are leading causes of bacterial meningitis – an infection of the membrane around the brain and spinal cord – and sepsis – a bloodstream infection, [2].
The CHMP recommendation serves as the basis for a European Commission licensing Decision. The CHMP is recommending that the European Commission grant Marketing Authorization for Menveo in all 27 European Union (EU) countries, which is expected during the first quarter of 2010. Regulatory review for Menveo by the US Food and Drug Administration is ongoing.
Upon licensure, Menveo is expected to be the first conjugate vaccine to be commercially available in Europe to help protect against four major groups of meningococcal bacteria. Meningococcal disease is a sudden, life-threatening illness that can lead to death within 24 to 48 hours of the first symptoms, , . Of those who survive, as many as one in five will suffer life-long after effects, such as brain damage, learning disabilities, hearing loss and limb loss.
“The Committee’s positive recommendation of Menveo is a significant advance in the fight against meningococcal disease,” said Professor Ray Borrow who heads the Health Protection Agency’s Vaccine Evaluation Unit in the UK. “Five groups of meningococcal bacteria cause the majority of meningococcal disease cases around the world. Since it is impossible to predict which meningococcal bacterial group one might come into contact with, a vaccine that offers effective protection against four of the groups should be extremely effective in preventing and controlling the disease. It is a welcome development.”
“This is an important milestone toward our vision to eradicate this devastating, deadly and unpredictable disease,” said Andrin Oswald, CEO of Novartis Vaccines and Diagnostics. “We are confident that broad coverage with Menveo will eventually be available to all age groups.”
Menveo was developed using conjugate technology, which was also used to develop Novartis Vaccines’ meningococcal group C conjugate vaccine, Menjugate®. A conjugate vaccine is developed by attaching a polysaccharide antigen – the key component of a vaccine that prompts the body to respond to infection – to a carrier protein. When utilized in a national immunization program, conjugate vaccines (such as those designed to help protect against Hib, pneumococcal and meningococcal group C disease) have reduced the number of people (both vaccinated and unvaccinated) who carry the bacteria that cause the disease.
Adolescents are particularly susceptible to meningococcal disease and are more likely to carry the bacteria than other age groups. In addition, adolescents and young adults have relatively high death rates from meningococcal infection. A study in the United States found that nearly a quarter of meningococcal infections in 15- through 24-year-olds were fatal[8].
Menveo has been administered to more than 18,500 people and is currently in multiple Phase III clinical studies in infants and toddlers worldwide.
About meningococcal disease
Meningococcal disease is a sudden, life-threatening illness that progresses rapidly and can lead to death within 24 to 48 hours of the first symptoms. Meningococcal infection is a leading cause of bacterial meningitis — an infection of the membrane around the brain and spinal cord — and sepsis – a bloodstream infection[2]. The bacteria that cause meningococcal disease — Neisseria meningitides — can be divided into groups. Five groups of meningococcus cause the majority of all meningococcal disease cases around the world.
Because the initial symptoms of meningococcal disease can be similar to flu-like symptoms, it can be difficult for health care professionals to diagnose early. Classic symptoms, such as neck stiffness and petechial rash, do not appear until relatively late in the illness — 13-22 hours after the first symptoms appear.
According to the World Health Organization (WHO), approximately 5-10 percent of those who contract meningococcal disease will die, even if they are diagnosed and receive treatment. Of those who survive meningococcal disease, as many as one in five will suffer life-long side effects, such as brain damage, learning disabilities, hearing loss and limb loss.
Infants are the most vulnerable population and represent the greatest unmet need. About 6-10 percent of children under 12 months of age who contract meningococcal disease will die[9].
About Novartis Vaccines’ global meningococcal franchise
Menveo vaccine is based on the same proprietary technology Novartis Vaccines pioneered to produce Menjugate®, a meningococcal serogroup C conjugate vaccine approved outside the U.S. since 2000 for use in individuals from 2 months of age through adulthood. The company has already distributed more than 26 million doses of Menjugate around the world. Novartis also produced MenZB®, a vaccine against a strain of meningococcus B specific to a recent outbreak in New Zealand.
Novartis Vaccines is a global leader in providing vaccines to protect against deadly meningococcal disease. Through industry-leading scientific expertise, the company is focused on extending critical meningococcal vaccines research. In addition to developing Menveo vaccine, Novartis Vaccines is developing a recombinant protein vaccine for its potential to provide broad coverage against multiple strains of serogroup B, for which no vaccine is currently available.‹
[Menveo, which was approved by Europe’s CHMP in Dec 2009 (#msg-44704381), figures to be a solid midsized product for NVS. The comparator in the phase-3 trial that formed the basis for approval was Menactra, the vaccine from SNY that generated $600M in worldwide sales in 2009. (Menactra has been on the US market since 2005 for subjects aged 11-55 and since 2007 for subjects aged 2-10.) Menveo was numerically better, although not statsig better, than Menactra in subjects aged 11-18 as reported here and in #msg-29074356; both PR’s are silent on the head-to-head comparison for subjects aged 19-55, so presumably Menveo was not better in this subgroup. (Menveo and Menactra are unrelated to the type-B meningitis vaccine that’s routinely given to infants as part of the standard vaccination package.)]
• Menveo licensed in 11-55 year olds to help protect against potentially deadly meningitis and sepsis caused by four common vaccine-preventable serogroups[1]
• Meningococcal disease causes approximately 50,000 deaths globally each year, many of which could be prevented through vaccines[2]
• Novartis plans to seek licensure of Menveo in infants and children 2-10 years of age
Basel, February 22, 2010 - Novartis announced that Menveo® (Meningococcal (Groups A, C, Y and W-135) Oligosaccharide Diphtheria CRM197 Conjugate Vaccine), a quadrivalent meningococcal conjugate vaccine was approved by the US Food and Drug Administration (FDA) for active immunization to prevent invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135 in people 11 to 55 years of age[1].
Meningococcal disease infects more than 500,000 people each year, leading to more than 50,000 deaths globally[2]. As many as 1 in 7 patients who contract meningococcal disease die from it[3]. Approximately 1 in 5 meningococcal disease survivors suffer serious, permanent and devastating side effects, including limb amputations, seizures, paralysis, hearing loss and learning disabilities[4]. Meningococcal disease is a leading cause of bacterial meningitis, which is an infection of the membrane around the brain and spinal cord, and sepsis, an often life-threatening bloodstream infection[4], [5]. Even with early and appropriate treatment, the disease may progress rapidly and is potentially fatal, often within 24-48 hours of onset of symptoms[6].
"The FDA approval of Menveo is an important milestone for adolescent immunization in the United States. According to CDC estimates, approximately 16 million adolescents between the ages of 11 and 18 are at risk and remain unprotected against meningococcal disease," said Andrin Oswald, Division Head of Novartis Vaccines and Diagnostics. "Meningococcal disease is particularly distressing because it can rapidly kill or debilitate previously healthy adolescents. For this reason, we are dedicated to helping eradicate meningococcal disease in the United States and around the world."
In the United States, incidence of meningococcal disease varies, ranging between 1,000 and 3,000 cases per year[4].
FDA approval of Menveo was based on a Phase III head-to-head clinical trial that compared Menveo to the other US-licensed ACWY meningococcal conjugate vaccine[SNY’s Menactra] among subjects 11 to 55 years of age. The trial, which was broken into two subsets - adolescents, age 11 to 18, and adults, age 19 to 55 - measured for each of the four serogroups both the percentage of subjects who achieved an immune response as measured by seroresponse and proportions achieving human serum bactericidal antibody (hSBA) titers >=1:8. Additionally the study examined antibody level as measured by geometric mean titers (GMT)[1].
"Even with early and appropriate treatment, patients can die from meningococcal disease, often within 24-48 hours of onset of symptoms[6]. Menveo achieved a higher immune response than the other currently available vaccine, which is very reassuring," said Keith S. Reisinger, MD, Medical Director, Primary Physicians Research, Inc., Pittsburgh, Penn. "With the FDA approval of Menveo, now healthcare providers in the United States have another option to help prevent this life-threatening invasive disease."
In study participants aged 11 to 18 years, Menveo met its primary endpoint for all four serogroups using hSBA seroresponse. The percentages of subjects who demonstrated an immune response (i.e., achieved an hSBA titer >=1:8) for each serogroup for Menveo and its comparator (the other currently US-licensed ACWY meningococcal conjugate vaccine) respectively, were: Serogroup A - 75: 67; serogroup C - 84: 84; serogroup Y - 88: 69; and serogroup W-135 - 96: 88[NVS evidently isn’t disclosing similar data for the subjects aged 19-55] [1].
The seroresponse with Menveo for serogroups A, Y and W-135, was statistically higher. However the clinical relevance of higher post-vaccination immune responses is not known.
In the same group, the levels of circulating antibodies (i.e., GMT) in those who received Menveo vs. those who received the comparator, respectively, were: Serogroup A - 29: 18; serogroup C - 59: 47; serogroup Y - 51: 18; and serogroup W-135 - 87: 44[1].
Since 2005, the Advisory Committee on Immunization Practices, a group of 15 experts who advise the US Centers for Disease Control and Prevention (CDC) on the control of vaccine-preventable diseases, has recommended routine immunization with a quadrivalent meningococcal conjugate vaccine for all adolescents, 11 to 18 years of age, college freshmen living in dormitories and people in other high risk groups who are 19 to 55 years of age[3].
Approval of Menveo is the result of 10 years of dedicated effort by Novartis Vaccines to provide a vaccine that can help protect people against meningococcal disease. The Menveo development program for other age groups continues in multiple Phase III clinical trials. Menveo has the potential to be utilized in a broad age range, and the company plans to seek supplementary licensures for use of the vaccine in other age groups. Data to support an indication for children 2 to 10 years of age is expected to be submitted in the first half of 2010. Novartis expects to file data to support an infant indication in 2011.
About meningococcal disease, a leading cause of bacterial meningitis
Because invasive meningococcal disease can progress so rapidly, high levels of circulating antibodies are critical for protection. Immune memory typically takes up to five days to develop, so there often is not enough time for immune memory to mount a protective response once the disease has started[7].
Five serogroups cause the majority of meningococcal disease worldwide: A, B, C, Y and W-135[8]. Distribution of serogroups varies widely from geographic region to region and changes over time[8]. Currently, in the United States, most disease is caused by serogroups B, C, and Y[3]. The prevalence of serogroup Y has increased over the last few years (from 9 percent of reported cases in 1990 to 1992 to 39 percent in 2006)[7]. Epidemiology of meningococcal disease is constantly changing[8], so it is impossible to determine which serogroups will result in the majority of disease cases year over year.
For more information, please visit www.meningitis.com.
About Novartis Vaccines' global meningococcal franchise
Novartis Vaccines is a global leader in providing vaccines to protect against deadly meningococcal disease. Through industry-leading scientific expertise, the company is focused on extending critical meningococcal vaccines research. In addition to developing Menveo vaccine, Novartis Vaccines is developing a recombinant vaccine for its potential to provide broad coverage against multiple strains of serogroup B, for which no vaccine is currently available.
Menveo vaccine is based on the same proprietary technology Novartis Vaccines pioneered to produce Menjugate®, a meningococcal serogroup C conjugate vaccine approved outside the US since 2000. The company has already distributed more than 41 million doses of Menjugate around the world and produced MenZB®, a vaccine against a strain of meningococcus B specific to a recent outbreak in New Zealand.
References
[1] Menveo® Highlights of Prescribing Information. February 2010. [2] World Health Organization. Meningococcal Position Paper. Weekly Epidemiological Record No. 44, 2002, 77, 329-340. [3] Centers for Disease Control and Prevention. Prevention and Control of Meningococcal Disease - Recommendations of the Advisory Committee on Immunization Practices. MMWR 2005; 54 (RR07): 1-21. [4] Centers for Disease Control and Prevention. Epidemiology and Prevention of Vaccine-Preventable Diseases (The Pink Book: Course Textbook). 10th Edition, 2nd printing. February 2008 update. [5] Centers for Disease Control and Prevention. Meningococcal Disease: Frequently Asked Questions. May 2008. [6] World Health Organization. Meningococcal Meningitis Fact sheet. May 2003. [7] Novartis Vaccines and Diagnostics, Scientific Platform: Meningococcal Vaccines, Revised December 11, 2008. [8] Schaffner, W. et al. The Changing Epidemiology of Meningococcal Disease Among US Children, Adolescents, and Young Adults. National Foundation for Infectious Diseases. November 2004.‹
Market Data 
Markets 
AI
