What is FDA announcing?
The FDA is announcing the approval of Trumenba, the first vaccine approved in the United States to prevent invasive meningococcal disease caused by Neisseria meningitidis serogroup B in individuals 10 through 25 years of age.
Trumenba is manufactured by Wyeth Pharmaceuticals Inc., a subsidiary of Pfizer Inc.
What is meningococcal disease?
Meningococcal disease is a life-threatening illness caused by bacteria that infect the bloodstream (sepsis) and the lining that surrounds the brain and spinal cord (meningitis). Neisseria meningitidis is a leading cause of bacterial meningitis. The bacteria are transmitted from person to person through respiratory or throat secretions (e.g., by coughing, kissing, or sharing eating utensils).
Even with appropriate antibiotics and intensive care, between 10 and 15 percent of people who develop meningococcal disease die from the infection. Another 10 to 20 percent suffer permanent complications, such as brain damage or limb loss.
How is Trumenba different than other FDA-approved meningococcal vaccines?
There are five main serogroups of meningococcal bacteria: A, B, C, Y, and W. The FDA has approved other vaccines to prevent invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W, but these vaccines do not protect against meningococcal disease caused by serogroup B. Trumenba prevents invasive meningococcal disease caused by Neisseria meningitidis serogroup B. Serogroup B disease is serious and accounts for approximately one-third of invasive meningococcal disease in the United States.
According to the Centers for Disease Control and Prevention, about 500 total cases of meningococcal disease were reported in the United States in 2012; of those cases, 160 were caused by serogroup B.
How was FDA able to determine the safety and effectiveness of Trumenba and approve it well under six months, the usual timeframe for a priority review?
The outbreaks of serogroup B meningococcal disease at two universities in the United States this past year underscored the urgent public health need for a safe and effective vaccine to prevent serogroup B meningococcal disease.
The FDA designated Trumenba as breakthrough therapy to facilitate the development, scientific evaluation, and approval of Trumenba.
The criteria for breakthrough therapy designation include that the product is intended to be used alone or in combination with one or more drugs to treat a serious or life threatening disease or condition and preliminary clinical evidence indicates that the product may demonstrate substantial improvement on a clinically significant study endpoint(s) over available therapies. Having the designation of breakthrough therapy provided the manufacturer more intensive FDA guidance on an efficient Trumenba development program, thereby facilitating the scientific evaluation during the Investigational New Drug (IND) application stage, an organizational commitment involving senior managers, and a “rolling” submission of the Biologics License Application (BLA). This allows sponsors to submit sections of the BLA to FDA for review as they are completed, as opposed to waiting to submit the complete BLA at one time.
Because of the public health importance of a vaccine against serogroup B meningococcal disease, the FDA directed its efforts to complete its evaluation of Trumenba as quickly as feasible.
How was the effectiveness of Trumenba determined?
Because serogroup B meningococcal disease in the United States is uncommon, the evaluation of the effectiveness of Trumenba to prevent serogroup B meningococcal disease was based on immune responses, as measured by antibodies, in vaccine recipients.
As background, serogroup B meningococcal disease can be caused by hundreds of different strains and the meningococcal bacterium includes many different proteins on its surface, which allow the bacteria to live in the bloodstream and cause disease. Vaccination of study participants with Trumenba induced antibodies to bacterial proteins that were shown to kill four different N. meningitidis serogroup B strains. These four strains, based on scientific judgment, are representative of strains that cause serogroup B meningococcal disease in the United States.
Three randomized studies were conducted in the United States and Europe in approximately 2,800 adolescents. Among study participants who received three doses of Trumenba, 82 percent had antibodies in their blood that killed all four strains in tests performed in a laboratory, compared with less than one percent before vaccination.
The FDA utilized the accelerated approval regulatory pathway to approve Trumenba. Accelerated approval is an example of an FDA expedited program. Accelerated approval allows the agency to approve products for serious or life-threatening diseases based on evidence of a product’s effectiveness that is reasonably likely to predict clinical benefit, reducing the time it takes for needed medical products to become available to the public. In FDA’s evaluation for accelerated approval, evidence of effectiveness was demonstrated by the ability of Trumenba recipients’ antibodies to kill the four representative serogroup B test strains. As part of the accelerated approval process, the manufacturer will conduct further studies to verify Trumenba’s effectiveness against diverse N. meningitidis serogroup B strains. The confirmatory studies will test Trumenba’s effectiveness to induce antibodies that kill ten additional strains of serogroup B that play a significant role in causing meningococcal disease in the United States.
How was the safety of Trumenba determined?
The safety of Trumenba was assessed in approximately 4,500 individuals who received the vaccine in studies conducted in the United States, Europe and Australia. The most commonly reported side effects by those who received Trumenba were pain and swelling at the injection site, headache, diarrhea, muscle pain, joint pain, fatigue and chills.
How many doses of Trumenba are needed?
The FDA approved a three-dose series for administration to individuals 10 through 25 years of age on a 0, 2 and 6-month schedule.
Is Trumenba the same vaccine that was used under an Expanded Access IND application in response to outbreaks at two U.S. universities in 2013?
No, the vaccine used in response to those outbreaks was Bexsero, which is manufactured by Novartis. Novartis has publically stated that a Biologics License Application (BLA) for Bexsero was submitted to the FDA in June 2014.
FDA regulations allow the use of a drug or vaccine that is not approved in the United States to treat serious or immediately life-threatening diseases or conditions when there are no comparable or satisfactory alternative treatment options. The mechanism allowing such use is known as an expanded access IND. In this case, the CDC is the sponsor of the IND for Bexsero. To allow use of an unlicensed vaccine under this mechanism, among other criteria, the FDA must first determine that the potential benefit to the vaccine recipient justifies the potential risk(s) of the vaccine and those potential risks are not unreasonable in the context of the disease or condition.
If an individual received a vaccine to prevent meningococcal disease caused by serogroups A, C, Y and W, will that vaccine suffice to protect against serogroup B?
No. The vaccine routinely administered to adolescents in the United States protects against the four meningococcal serogroups, A, C, Y, and W, but not against serogroup B.
Is Trumenba approved in other countries?
No, the United States is the first country to approve Trumenba.