In 2010 a Swiss company successfully completed Phase III trials for a groundbreaking vaccine to fight a rare but deadly strain of meningitis. Four years later, outbreaks of Meningitis type B (MenB) are spreading in college campuses across the United States, though the product still awaits approval by the Food and Drug Administration.
What a former FDA official attributes to "risk-aversion," the agency has yet to certify Bexsero, the first MenB vaccine made by Novartis, though it is already available in Europe, Australia, and Canada.
Since Bexsero is not approved, the FDA must grant "special permission" for universities with outbreaks, such as Princeton and the University of California, Santa Barbara, to obtain the vaccine, adding months to the deployment process.
The vaccine came too late for Emily Stillman, Stephanie Ross, and Aaron Loy.
Stillman, 19, a sophomore at Kalamazoo College in Michigan, was killed within 36 hours of contracting meningitis B, last February.
"My Emily was vaccinated. I felt safe," said Alicia Stillman, the girl’s mother. Emily had received the common vaccine for serogroups C and Y, which college-aged students receive before they enroll.
"I hope there will come a time it can be used routinely here," she said, of Bexsero. "It's a horrible, horrible disease."
Since Emily’s death, eight cases have been confirmed in Princeton, and four in UCSB, including Aaron Loy, a lacrosse player who had both of his feet amputated after contracting an infection in November.
On Tuesday, the Centers for Disease Control confirmed that Stephanie Ross, a mechanical engineering major at Drexel University, died from the same strain of meningitis found in the Princeton outbreak.
A meningitis infection can lead to death within 24 hours of the first symptoms, which include a sudden high fever, headache, and sensitivity to light. About one in 10 of those with the disease will die despite treatment, and one in five survivors will suffer from life-long disabilities such as brain damage, hearing loss, or limb loss.
Novartis has worked on its vaccine for 20 years. The results of testing in 2010 on more than 7,500 people, including 3,500 infants, led to its approval in the EU. The large majority of infants "achieved robust immune response against" the strain. The EU, Canada, and Australia all approved the vaccine in 2013.
The Centers for Disease Control and Prevention (CDC) said the FDA thinks the vaccine is safe, and has "concluded that the benefits of using the vaccine to prevent meningococcal disease outweigh the risks of possible adverse events in certain outbreak situations."
Despite this, the agency has been slow to approve the vaccine due to its "risk-aversion," according to Dr. Henry Miller, who served for fifteen years as a medical reviewer, special assistant to the commissioner, and founding director of its Office of Biotechnology at the FDA.
Based on his experience, Miller says there are two kinds of errors the FDA succumbs to: "Type I and Type II."
"A Type I error involves permitting something bad to happen (i.e. approving a product that turns out to be harmful), while a Type II error delays or prevents something beneficial (e.g., failing to approve a life-saving vaccine)," Miller wrote in Forbes in December.
The agency is so afraid of being blamed for approving drugs that could be harmful that it becomes stagnant, stopping itself from endorsing life-saving treatments, he said.
Not only does he fault the FDA and "their irresponsibility" for not approving Bexsero, Miller says Congress is liable for its lack of oversight.
"It’s a function of very poor, inadequate, incompetent oversight of the FDA by the congressional committees," Miller told the Washington Free Beacon. "Margaret Hamburg, the FDA commissioner, testified just last week before the Senate Health Committee and I don’t think it came up at all. They let her get away with a lot of stuff."
Miller said the House Energy and Commerce is "not much better." "So they’re certainly culpable in part, as well."
A bipartisan group of House members sent a letter to Hamburg on Feb. 7, asking the FDA to "take steps to prevent another MenB outbreak."
"Approval of this vaccine has been held up for three years by the U.S. FDA’s bureaucracy, despite the fact that there have been successful clinical studies," said the letter, led by Rep. Erik Paulsen (R., Minn.). "The FDA has slowed the testing and approval process, leading officials at the affected campuses to appeal to the government for special permission to import and administer the vaccine."
Reps. Dana Rohrabacher (R., Calif.), Marsha Blackburn (R., Tenn.), Leonard Lance (R., N.J.), Jackie Walorski (R., Ind.), and Gloria Negrete McLeod (D., Calif.) also signed on, asking the FDA to recognize "reciprocity" agreements with Europe to immediately approve the drug. The FDA could also expedite Bexsero’s license through the "accelerated approval" process, they said.
"This MenB vaccine is a total no-brainer," Miller said. "If Novartis requested accelerated approval, FDA should grant it. If Novartis hasn’t yet requested it, FDA should suggest it to them."
"Accelerated approval," introduced by the FDA in 1992, is meant for serious life-threatening illnesses where treatment is not yet authorized. Under the process, the FDA can expedite the deployment of drugs on the condition that the manufacturer proves its effectiveness in the near future. If the company does not complete more definitive studies, the FDA can withdraw its endorsement.
FDA Press Officer Tara Goodwin said the agency could not comment when asked why Bexsero has not received accelerated approval.
"The FDA cannot comment on the review of an application," she said. "However, Novartis has given the FDA permission to disclose that the firm plans to submit a biologics license application for Bexsero (serogroup B meningococcal vaccine) to the FDA for review in the second quarter of 2014."
"The FDA will continue to work closely with CDC, and will monitor the situation," Goodwin said. "The FDA's regulations (21 CFR 601.50 and 601.51) don't allow us to comment further."
A Novartis spokesperson said the company began discussions with the FDA in 2009 to pursue a license for Bexsero in the U.S.
"Recent outbreaks have demonstrated the urgent need for a licensed menB vaccine in the U.S.," Elizabeth Power, director of Global Media Relations at the Novartis
Corporation, said. "We therefore plan to file Bexsero in the U.S. as early as Q2 2014. Exact timing and length of the review process depends on guidance from the FDA."
The FDA has defended its actions with regard to Bexsero, saying it made the vaccine "available quickly to universities affected."
"A recent column indicated the Food and Drug Administration has inappropriately delayed access to a meningitis B (MenB) vaccine in the U.S.," said Dr. Karen Midthun, director of the FDA’s center for Biologics Evaluation and Research, last week. "This assertion is misleading. The FDA is committed to responding rapidly to public health threats and did so in this case."
Miller said the FDA’s comments were "totally absurd."
"If you believe that, you believe that if you want to keep your health care plan you can," he said. "It’s just absurd. It should take days, and instead it took months."
"This is really just atrocious," Miller said. "It’s atrocious. And it’s a no-lose situation for the FDA, that’s the thing. Because we know the drug is safe and effective."
In a response to Rep. Blackburn on March 5, the FDA said they recognize that meningitis B outbreaks are "very serious," and "we appreciate your concerns."
Sally Howard, deputy commissioner for Policy, Planning, and Legislation at the FDA, said, "We have been working closely" with Novartis to "expeditiously make available this product to the affected universities under FDA’s expanded-access program for investigational products."
The FDA has deployed Bexsero to fight the outbreaks on college campuses, though shipments to Princeton were delayed by two months because of its designation as an "Investigational New Drug" (IND).
"Under this process, many weeks are required to gain administrative approvals, organize supply and delivery of the vaccine from countries where it is being used, and decide how many vaccination programs will be managed at local sites," Novartis said.
"Granting a U.S. license for Bexsero for use in all adolescents and young adults would enable immediate response to future outbreaks and allow US families to have access to a vaccine to help protect against MenB," they said.
In the meantime, parents are going to great lengths to obtain Bexsero. One mother spent $4,000 sending her son to London to get the vaccine before she would let him return to UCSB.