Biotech Values

[DewDiligence]

FDA Approves NVS’ Menveo Meningitis Vaccine

[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.)]

http://www.novartis.com/newsroom/media-releases/en/2010/1386845.shtml

›February 22, 2010 07:05 CET

• 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.‹