Therapy Analysis - Influenza
Current therapies for seasonal influenza
Immunisation remains the current mainstay of therapy for seasonal 'flu, and with the clearly very large market available there are many types of vaccine available. Fluzone, developed by Sanofi-Pasteur, is an injectable influenza vaccine reformulated each year to match the predicted predominant strain for the coming season. It is available in the US for influenza prophylaxis in all populations aged over 6 months. Fluzone HD, an intramuscular formulation, is currently awaiting US approval. In a randomized, double-blind Phase III trial in 65 patients, Fluzone HD achieved significantly higher haemaglutinin inhibition titres for all three influenza strains, compared to a standard seasonal vaccine. Aviron (a subsidiary of MedImmune) has developed FluMist, a cold-adapted, trivalent influenza vaccine for intranasal administration. It consists of a modified live virus containing the influenza viral core with the coat of one or more virulent strains. In a US Phase III trial in 15000 patients during the 2004/2005 'flu season, it reduced 'flu-like illness in children and adults by 23% and 27%, respectively. Use of prescription and OTC drugs to treat 'flu-like illness was also reduced by 38% and 31%, respectively. In 8475 children aged 6-59 months, cases of influenza were reduced by 55% compared to a standard injectable vaccine. FluMist is launched in the US for the prophylaxis of influenza A and B virus in children and adults, and is awaiting approval in the EU.
A new approach to influenza prophylaxis is Sanofi- Pasteur's Intanza, a trivalent vaccine against influenza A strains H1N1 and H3N2, as well as influenza B strains. It is delivered intradermally by microinjection, where the high concentration of immune cells produces a rapid immune response. In a previous Phase II trial in 738 patients, it showed higher seroprotective immune responses compared to intramuscular vaccination. In clinical trials in over 7000 adults, it showed a superior level of seroprotection against all strains of influenza compared to standard intramuscular vaccination. Intanza is approved in the EU, and will be available for the 2009/2010 'flu season. A US filing is expected in 2009.
GlaxoSmithKline is developing a split-inactivated seasonal influenza vaccine. It is currently in Phase III trials, including a Phase III trial in 3500 volunteers. A randomized, double-blind Phase III trial in 4440 volunteers, to assess safety and immunogenicity, was conducted. In previous Phase II trials, in patients aged 65 years and over, the vaccine showed improved immunogenicity over a currently used 'flu vaccine, with patients reaching immune responses comparable to young adults. Seroprotection rates were 25% higher than those in the control group.
One interesting vaccine in the earlier stages of clinical development is NasVax's sphingolipid-derived adjuvanted influenza vaccine. The liposomal vaccine can be delivered intranasally, or by intramuscular or subcutaneous injection. In a Phase I/II trial in 100 patients to assess safety, efficacy and immunogenicity of an intramuscular dose, the vaccine increased rates of geometric mean titre at one, three and six months postdose compared to a commercial vaccine. Side effects were dose-related and milder in elderly subjects. Intranasal administration of the vaccine has also been evaluated in a Phase I/IIa trial, where preliminary results showed it to be safe and well tolerated.
