Applied Clinical Trials
The bacterial meningitis outbreak at Princeton University in recent weeks has raised questions about why there is no vaccine in US to prevent this deadly disease, when such a therapy is approved in Europe and Australia.
The bacterial meningitis outbreak at Princeton University in recent weeks has raised questions about why there is no vaccine in US to prevent this deadly disease, when such a therapy is approved in Europe and Australia. The current Princeton health danger prompted the Centers for Disease Control and Prevention (CDC) to request emergency import of the vaccine, and the Food and Drug Administration approved that move, authorizing an IND (investigational new drug application) for Novartis’ Bexsero vaccine. New reports of additional meningitis B cases in California may spark further discussion about ensuring U.S. access to protection against this dangerous infection.
The situation illustrates the complexities of vaccine development, approval and reimbursement at home and abroad. Studies to document vaccine safety usually require testing in thousands of healthy individuals, plus certain high-risk populations. There are four meningitis vaccines licensed in the US, but they protect against four other meningococcal disease strains, and not B, which has proven more difficult to attack.
Moreover, meningitis B is not that prevalent in the US, so Novartis and other vaccine makers have concentrated clinical trials for B preventives in Europe, Australia and other regions. The resulting study data supported market approval for Bexsero in the European Union in January (2013) and more recently in Australia. More trials have been launched in Latin America and even Canada, but not in the US where Novartis did run a small, early trial on adolescents several years ago. Meningitis is most deadly in infants and very young children, and testing in those populations raises difficult risk-benefit calculations for a relatively uncommon condition.
In April 2011, the FDA advisory committee on vaccines and related biological products discussed the effectiveness of meningococcal vaccines in young children and approaches for demonstrating effectiveness in serogroup B vaccines. Representatives from Novartis and Pfizer made presentations on new but differing approaches for developing effective therapies and new surrogates for demonstrating protection.
Novartis says it is discussing a “pathway to licensure” with FDA and “evaluating its Phase III plans” for the US and other regions. But market approval of a meningitis B vaccine in the US may take much longer because Novartis and other vaccine makers now appear more interested in developing a combination vaccine that will cover all five meningitis strains.
To some extent, that decision reflects problems with reimbursement for new vaccines, which largely comes from public health agencies. Novartis received a blow in July when the United Kingdom’s Joint Committee on Vaccination and Immunisation advised against adding Bexsero to its routine vaccination program. The Committee is reconsidering that recommendation, which was based largely on cost-benefit considerations: whether it is worth the money to vaccinate some 800,000 infants a year when only 1800 cases of the disease are found in children in the UK each year, and there are concerns that the vaccine may be only 73% effective.
These developments have spurred more talk about Novartis selling its vaccine business, which has struggled to be profitable, according to market analysts. Novartis recently announced the sale of its blood transfusion diagnostics unit, which is housed with its vaccines unit.
Researchers and patient advocates for more effective meningitis vaccine point out that cost-effectiveness studies often fail to assess prevention appropriately. They also fear that a final UK non-coverage decision for Bexsero could discourage vaccine research in general. Coverage certainly would be easier to justify for an all-strain meningitis vaccine, but that may involve years of more testing.