FDA Advisers Urge Approval of New Flu Vaccine for Seniors

Alicia Ault

September 15, 2015

SILVER SPRING, MD — A US Food and Drug Administration (FDA) advisory panel has recommended approval of Fluad (Novartis), a new influenza vaccine that promises to offer enhanced effectiveness in patients aged over 65 years.

The Vaccines and Related Biological Products Advisory Committee voted 11-1 that the vaccine was effective and 10-2 that it was safe, with one member abstaining from both votes.

The FDA usually follows its panels' advice.

Fluad, made by Novartis Vaccines and Diagnostics, is an inactivated, trivalent vaccine. Unlike the 12 currently available flu vaccines for people aged over 65 years, Fluad contains an adjuvant designed to stimulate a greater immune response. Novartis is seeking accelerated approval, which means it will have to conduct a postmarketing trial to confirm the vaccine's clinical benefit.

The FDA allows accelerated approval of a flu vaccine if there is a current shortage, said Marion Gruber, PhD, director of the Office of Vaccines Research and Review at the FDA's Center for Biologics Evaluation and Research. Year-to-year, there has not been enough vaccine to cover all those who are considered eligible for vaccination by the Centers for Disease Control and Prevention, said Dr Gruber.

Panel member Mark Sawyer, MD, professor of clinical pediatrics at the University of California, San Diego, said the notion of a shortage was dubious given how much vaccine is discarded at the end of each season. "But we are in need of an adequate vaccine for seniors," he said.

Pedro Piedra, MD, professor of molecular virology and microbiology at Baylor College of Medicine in Houston, Texas, agreed that a better vaccine is needed for older Americans. Fluad looks to fit the bill, he said. "There's clear evidence for the H3N2 component that this vaccine is superior to [the] comparator vaccine," said Dr Piedra.

Of the three flu strains that generally circulate, the H3N2 types tend to be more lethal to people aged over 65 years.

Long Marketing History

Fluad was first approved in Europe in 1997 and is currently sold in more than 38 countries, including Canada. The FDA said that there have been no safety issues with more than 81 million shots administered.

The adjuvant, known as MF59, contains a biodegradable oil — squalene — which is mixed with sodium citrate dihydrate and citric acid monohydrate and the surfactants polysorbate 80 and sorbitan trioleate. The adjuvant and vaccine are manufactured in Italy according to United States manufacturing processes.

Some committee members asked why the adjuvant wasn't subject to separate approval. Dr Gruber said that, by law, vaccine adjuvants were not considered active ingredients that required approval.

But panelist Vicky Pebsworth, PhD, RN, director of patient safety at the National Vaccine Information Center, said that there were too many unanswered questions about MF59's safety. She voted against approval. "Why do we have to rush to push through something that has the potential to cause harm in some people?" she said.

Novartis conducted a single pivotal study to gain US approval. The randomized, active-controlled, observer-blind, multicenter clinical trial compared the safety and immunogenicity of Fluad with Agriflu (an unadjuvanted trivalent inactivated influenza subunit vaccine licensed in the US; Novartis) in patients aged 65 years or older. The study was conducted in the Philippines, Colombia, Panama, and the US, with patients assigned to receive one of three lots of Fluad (3552 patients) or one lot of Agriflu (3552 patients).

The company was able to show that the three lots of Fluad were equivalent in efficacy and noninferior to Agriflu. Fluad was superior to Agriflu for H3N2 strains.

More people receiving Fluad experienced local and systemic side effects (43% overall) within the first week postvaccination when compared with Agriflu (33%). But the FDA said that severe adverse events were similar between the two vaccines.

Novartis is proposing to step up postmarketing surveillance if Fluad is approved. Among other aspects of the proposal, vaccine recipients will be told to report any events occurring within a week of vaccination. They'll be given a call-center number and a card with information on the brand, the batch number, and the date they received the shot.


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