GlaxoSmithKline plc (GSK) has presented the results from five phase III studies investigating its two candidate quadrivalent influenza vaccines (QIVs) at the Influenza Vaccines for the World (IVW) congress in Valencia, Spain and the Infectious Diseases week (IDweek) congress in San Diego, USA.  GSK’s candidate QIVs contain two influenza A strains and two influenza B strains to potentially help broaden protection against seasonal influenza as compared to currently approved trivalent vaccines (TIV) containing two A influenza strains and one B influenza strain.

Four immunogenicity and safety studies in children and adults showed that both QIVs are highly immunogenic against all four influenza strains contained in the vaccine.  The addition of a fourth strain in the QIVs did not negatively affect the antibody response of the other three strains in common with the TIV. Therefore, both QIVs met the primary endpoint of non-inferiority for the common influenza strains across all age groups studied (3-17 years, 18-64 years and > 65 years). In addition, both QIVs met the superiority endpoint for the additional B influenza strain.  The reactogenicity and safety of the QIVs were comparable to TIV.

In the fifth study - an efficacy study conducted in children aged 3-8 years - the QIV met the primary endpoint of vaccine efficacy, demonstrating that it can help protect against mild as well as moderate-severe cases of influenza.

GSK is developing the candidate QIVs from two manufacturing facilities: one in Dresden, Germany (referred to as ‘D-QIV’) and the other in Québec, Canada (referred to as ‘Q-QIV’).

Both QIVs are currently not approved or licensed anywhere in the world for the prevention of seasonal influenza.  Regulatory submissions for D-QIV in the US and EU were initiated in February 2012. In addition, a regulatory dossier for Q-QIV in the US was submitted in October 2012.

The five reported phase III studies were conducted in over 17,000 adults and children.  The quadrivalent vaccine evaluated in the studies contained two influenza A strains: A/H1N1 and A/H3N2 and one strain from each of the influenza B lineage (called Victoria and Yamagata). The TIVs contained either a B influenza strain from the Victoria lineage (TIV-Vic) or the Yamagata lineage (TIV-Yam).

he Phase III clinical programme comprises two parallel developments for Q-QIV and D-QIV. Each programme contains three studies: an immunogenicity and safety study in adults, an immunogenicity and safety study in children and an efficacy study in children. All immunogenicity and safety studies as well as one efficacy study (with Q-QIV) have completed. The D-QIV efficacy study in approximately 8000 children is ongoing.

Seasonal influenza may cause three to five million cases of severe illness and up to 500,000 deaths per year worldwide. Two distinct lineages of Influenza B – Victoria and Yamagata – have been widely circulating since 2002.  In the past decade, various degrees of mismatch have frequently occurred between the B strain included in trivalent vaccines and the B strain that actually circulated, causing an increased risk of morbidity across all age groups – children, adults and the elderly.