The non-profit National Vaccine Information Center (NVIC) is questioning the basis for the fast tracked licensure by the U.S. Food and Drug Administration (FDA) of a squalene-adjuvanted influenza vaccine for use in seniors over age 65. The Novartis MF59 adjuvanted Fluad vaccine was approved for accelerated licensure by the FDA Vaccines and Related Biological Products Advisory Committee (VRBPAC) on Sept. 15, 2015 primarily using limited immunogenicity and safety evidence from a small clinical trial in which only about 1,000 healthy Americans over age 65 were given the adjuvanted vaccine.1 2
“Novartis failed to demonstrate that squalene adjuvanted Fluad was more effective or safer than an unadjuvanted influenza vaccine in the small clinical trial being used to justify accelerated licensure. In fact, Fluad was shown to be far more reactive and, in some studies, the vaccine was associated with even more serious reactions in the elderly when given a second time,” said NVIC Co-founder and President Barbara Loe Fisher.
At public comment time, Fisher asked the FDA advisory committee, “Why does Fluad need to be fast tracked to licensure for the elderly without additional evidence? There is public concern that fast tracking Fluad is really about fast tracking MF59 to licensure so it can be added to lots of new vaccines targeting infants, pregnant women and every American without adequate evidence for safety or effectiveness.”3
Before the FDA advisory committee had taken a vote on whether Novartis had demonstrated the safety and effectiveness of Fluad in seniors, agency officials indicated they would approve accelerated licensure of the vaccine even though fast tracking is supposed to be reserved for instances when there are vaccine shortages. There are nine influenza vaccines licensed by the FDA as safe and effective for seniors, including two high dose options, and the Centers for Disease Control (CDC) estimates more than 170 million doses of influenza vaccine will be delivered to the U.S. market for the 2015-2016 flu season.4
Although MF59 is bioactive and designed to stimulate a strong immune response, FDA does not require that vaccine adjuvants be proven safe in a placebo controlled trial and they are not licensed separately.5 Fluad will be the first influenza vaccine licensed in the U.S. containing squalene, a controversial oil in water adjuvant that has been linked with development of autoimmunity, narcolepsy and other immune and neurological disorders.6
In her Sept. 15 public statement at the FDA advisory committee meeting, Fisher pointed out that the Novartis clinical trial did not provide sufficient evidence for fast track licensure of Fluad when:
- It is known that responses to vaccination are affected by genetic factors and only 30 percent of the Fluad study population was ethnically representative of U.S. seniors over age 65;
- The majority of Fluad study participants did not have heart, lung and kidney disease or other chronic health conditions that affect two-thirds of U.S. seniors, although chronically ill seniors will be recipients of Fluad after licensure;
- Fluad produced a much higher number of pain, tenderness, redness and swelling reports; a higher number of systemic adverse reaction reports and more deaths and cases of new onset chronic disease;
- The study did not evaluate the safety of giving repeated doses of squalene adjuvanted Fluad year after year to seniors with multiple chronic conditions;
- There is no information on how Fluad performs when given simultaneously with other vaccines (such as pneumococcal vaccine).
NVIC is a charitable educational organization founded in 1982 to prevent vaccine injuries and deaths through public education. It does not make vaccine use recommendations and advocates for the inclusion of informed consent protections in U.S. vaccine policies and laws. NVIC monitors vaccine science, policy and law and provides public comment at federal vaccine advisory committee meetings.
1 FDA. Briefing Document: Influenza Vaccine, Adjuvanted Fluad, Novartis Vaccines and Diagnostics, Inc, Applicant.
2 Novartis. FDA Advisory Committee Briefing Document: Fluad, Seasonal Adjuvanted Trivalent Influenza Vaccine (aTIV).
3 Fisher BL. Public Comment Statement Opposing FDA Fast Track Licensure of Fluad. VRBPAC Sept. 15, 2015 Meeting.
4 CDC. Seasonal Influenza Vaccine Supply for the U.S. 2015-2016 Influenza Season. Aug. 19, 2015.
5 FDA. Briefing Document: Influenza Vaccine, Adjuvanted Fluad, Novartis Vaccines and Diagnostics, Inc, Applicant. Pages 4 and 5.
6 See Reference #3.