After eight cases of group B meningococcal disease at Princeton University and four cases at University of California, Santa Barbara, health authorities have taken an unusual pathway to using a vaccine that is not licensed in the United States.
More than 5,000 Princeton students and staff members with certain medical conditions have received one dose of a meningococcal serogroup B vaccine approved for use in the outbreak by the FDA under an Expanded Access to Investigational New Drug protocol. (I have written about IND approval in the context of vaccines for emergent diseases and biological attacks.) Students will receive the second of the two needed doses in February.
Regulatory agencies in European Union, Canada, and Australia approved this vaccine in 2013, but the US FDA has not reviewed it for use here. Its unwieldy generic name is Meningococcal group B Vaccine [rDNA, component, adsorbed], though it is most often referred to by its trade name, Bexsero. Novartis manufactures the vaccine at sites in Europe.
The vaccine uses four antigens from serogroup B strains that provide protection from about 78% of the more than 1,000 identified strains of type B.
The existing US-licensed meningococcal vaccine is ineffective against group B meningococcal bacteria, though it protects against strains from the A, C, Y, and W-135 serogroups, which have been more common in this country.
In the United States in 2012, states reported 551 cases of disease from meningococci, with 110 cases of disease from group B meningococci and 161 cases from serogroups A, C, Y, and W-135. In 260 cases of meningococcal disease, the serogroup was unknown.
I spoke with Mary Broach, mother of a current Princeton freshman who received the first dose of the vaccine in December. Broach recalls being aware of the outbreak when she took her child to school in August: signs in restrooms urged students to be careful with hand hygiene because of the outbreak on campus the past spring. A few more cases emerged in the fall. Her child, Broach says, was not particularly worried about the outbreak, and they both viewed the six cases to date out of 6,000 students as rare events.
Those rare events, however, seemed a bit less rare in late November, when the eighth case was reported: Broach’s child is acquainted the student who became ill.
I asked Broach if she and her child found it difficult to make the decision to take the vaccine, but she said it wasn’t unduly hard. That the vaccine was approved in other countries, that her child knows another student who’d received the vaccine abroad, and that a family friend who is a doctor recommended taking the vaccine all helped them make the decision to accept the vaccine.
Novartis has completed phase 2 trials of a combination meningococcal serogroups A, C, Y, W-135, and B vaccine for potential licensure in the United States. A spokesperson for Novartis informed me that the company is evaluating plans to advance the vaccine into phase 3 trials. Given how long phase 3 trials take and the time required for FDA review and approval, it’s unlikely that this new vaccine will be available soon.
I asked History of Vaccines advisor and infectious diseases physician Thomas Fekete, MD, FCCP, to comment about potential use of the vaccine here in the United States. He wrote,
The number of cases of reported N. meningitis infection nationally is about 550, which is less than 2 cases per million population. It would be tremendously expensive to vaccinate enough people to prevent all cases of N. meningitis infection. The challenge is mammoth.
A brand new vaccine for general use needs to be tested appropriately because a huge number of people must take the vaccine to prevent even one case of a potentially dangerous illness. We would not tolerate a 1/10,000 serious adverse event rate for that vaccine, because that exceeds the rate of the disease.
The particulars that surround an active outbreak are different. The risk is probably greater for a few weeks, and the anxiety and fear of infection is also raised. With full information, adults (perhaps with their parents’ consent if they are minors) can try to understand the risk/benefit and make a choice. I don’t think we can yet frame this vaccine as one that conveys true herd immunity, but if that is true, this could be a secondary benefit in the midst of an outbreak. Still, it’s a tough choice.
Paul A. Offit, MD, is another advisor to this project. He told me, “Bexsero has been tested in thousands of people and shown to be safe as well as induce antibodies that would protect against infection. If either of my two children (who are both currently in college) were exposed to this infection, I wouldn’t hesitate to give them the vaccine.”
UC Santa Barbara students have not yet been offered the chance to take Bexsero: in late December, the CDC initiated an Investigational New Drug Application in response to the four cases of group B meningococcal infection that were reported in November. FDA has not yet approved the application, though, if the timeline in the Princeton case is an example, then a decision should be announced any day.
[UPDATE 2/4: On January 31, the CDC announced that the FDA had approved Bexsero for use at UCSB. The vaccine will be made available to the more than 19,000 undergraduates and certain other community members beginning February 24, 2014.]
CDC. Serogroup B Meningococcal Vaccine and Outbreaks. http://www.cdc.gov/meningococcal/outbreaks/vaccine-serogroupB.html
Bexsero EU Prescribing Information. http://ec.europa.eu/health/documents/community-register/2013/20130114125155/anx_125155_en.pdf
CDC. Final 2012 Reports of Nationally Notifiable Infectious Diseases. MMWR. August 23, 2013 / 62(33);669-682. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6233a6.htm
Novartis Vaccines. Bexsero R&D Timeline. http://www.novartisvaccines.com/downloads/meningococcal-disease/Infographic_Bexsero_R&D_Timeline_v_71913.pdf
Tseng E. Princeton Expected to Make Decision on Unapproved Vaccine Monday. The Princetonian. 11/15/2013. http://dailyprincetonian.com/news/2013/11/breaking-trustees-to-consider-emergency-meningitis-vaccines-for-princeton-community/
US Food & Drug Administration. Emergency Use of an Investigational Drug or Biologic. http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/InvestigationalNewDrugINDApplication/default.htm#Emergency