Results from five phase III studies presented for GSK’s two candidate quadrivalent influenza vaccines

Issued: London UK

GlaxoSmithKline plc (GSK) today announced that results from five Phase III studies investigating its two candidate quadrivalent influenza vaccines (QIVs) were presented at the Influenza Vaccines for the World (IVW) congress in Valencia, Spain and the Infectious Diseases week (IDweek) congress in San Diego, USA in October.  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.

About GSK’s QIV Clinical Studies

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).

Immunogenicity and safety studies in adults

In the first double-blind, randomised study (NCT01196975) in 1703 adults, Q-QIV met the superiority endpoint (demonstrated if the 95% confidence interval (CI) lower limit (LL) for the geometric mean titre (GMT) ratio was =1.5) compared to TIV-Vic and to TIV-Yam for the additional B strain.  Q-QIV also met the primary endpoint of non-inferiority (demonstrated if the 95% CI upper limit (UL) for the GMT ratio was =1.5) compared to each TIV group for the vaccine strains in common.  Consistency of manufacturing Q-QIV was also demonstrated. Adverse events were in similar ranges in the three groups.  Injection site pain was themost common solicited local symptom reported by 59.5% subjects in the Q-QIV group, and 44.7% in the TIV-Vic, and 41.2% in the TIV-Yam group.

In the second double-blind, randomised study (NCT01204671) in 4656 adults, D-QIV met the superiority endpoint versus TIV-Vic and versus TIV-Yam for the additional B strain.  D-QIV also met the non-inferiority endpoint compared to each TIV group for the vaccine strains in common.  Consistency of manufacturing Q-QIV was also demonstrated.  Adverse events were in similar ranges in the three groups. Injection site pain was the most common solicited local symptom reported by 36.4% subjects in the D-QIV group, and 36.8% in the TIV-Vic, and 31.3% in the TIV-Yam group.

Immunogenicity and safety studies in children

In the first double-blind, randomised study (NCT01198756) in 2793 children aged 3–17 years, Q-QIV met the non-inferiority endpoint (demonstrated if the 95% CI UL for the GMT ratio was 1.5 and the seroconversion rate (SCR) difference was 10%) to each TIV group for the vaccine strains in common. Q-QIV met the superiority endpoint (demonstrated if the 95% CI LL for the GMT ratio was >1.5 and the SCR difference was > 10%) to TIV-Vic and TIV-Yam for the additional B strain.  Adverse events were in similar ranges in the three groups.  Injection site pain was the most common solicited local symptom reported by 65.4% subjects in the Q-QIV group, and 54.6% in the TIV-Vic, and 55.7% in the TIV-Yam group.

In the second double-blind, randomised study (NCT01196988) in 2738 children aged 3-17 years D-QIV met the non-inferiority endpoint versus both TIV-Vic and TIV-Yam for the vaccine strains in common and met the superiority endpoint versus TIV-Vic and TIV-Yam for the additional B strain.  Adverse events were in similar ranges in the three groups.  Injection site pain was the most common solicited local symptom reported by 43.7% patients in the D-QIV group, and 42.4% in the TIV-Vic, and 40.3% in the TIV-Yam group.

Efficacy study in children

In this randomised study (NCT01218308) of 5168 children aged 3-8 years, vaccine efficacy of the Q-QIV against any influenza (defined as fever >37.8°C and a respiratory symptom) was 55.4% (95% CI 39.1, 67.3). The efficacy against moderate to severe influenza (defined as fever >39°C or acute otitis media, or signs of lower respiratory tract infection or extra pulmonary complication) was 73.1% (97.5% CI 47.1, 86.3).

About GSK’s quadrivalent influenza vaccines

The 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.

About Seasonal Influenza

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.

GlaxoSmithKline – one of the world’s leading research-based pharmaceutical and healthcare companies – is committed to improving the quality of human life by enabling people to do more, feel better and live longer.  For further information please visit www.gsk.com

Cautionary statement regarding forward-looking statements
Under the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995, GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Factors that may affect GSK' s operations are described under 'Risk factors' in the 'Financial review & risk' section in the company's Annual Report 2011 included as exhibit 15.2 to the company's Annual Report on Form 20-F for 2011.