Sanofi Pasteur Presents Phase III Data for Investigational Quadrivalent Influenza Vaccine

SWIFTWATER, Pa., Oct. 22, 2012 /PRNewswire/ -- Sanofi Pasteur, the vaccines division of Sanofi (EURONEXT: SAN andNYSE: SNY), presented today an overview of Phase II and Phase III clinical trials for its investigational quadrivalent influenza vaccine (QIV). Three clinical trials have been conducted to evaluate the safety and the immune response to the quadrivalent influenza vaccine in children, adults and the elderly. All three studies demonstrated that the safety and immunogenicity profiles of QIV were similar to licensed Fluzone^® (Influenza Virus Vaccine). The addition of a second influenza B strain in the vaccine afforded coverage against that strain with no corresponding negative impact on the immune response to the other influenza strains in the vaccine.

The data were presented at IDWeek™, the first joint meeting of the Infectious Disease Society of America (IDSA), the Society for Healthcare Epidemiology of America (SHEA), the HIV Medicine Association (HIVMA) and the Pediatric Infectious Diseases Society (PIDS). Sanofi Pasteur announced on October 18^th that the U.S. Food and Drug Administration (FDA) accepted its supplemental Biologics License Application for the quadrivalent formulation of its Fluzone vaccine for full review. Sanofi Pasteur is seeking FDA licensure of Fluzone quadrivalent vaccine for active immunization of children and adults 6 months of age and older for the prevention of influenza disease caused by influenza virus subtypes A and types B contained in the vaccine.

"Rates of hospitalization and death from influenza B are higher than those seen with A(H1N1) and, overall, influenza B is a significant cause of absenteeism, clinic visits, hospitalizations and complications across all ages, but especially in children," said David Greenberg, M.D., Senior Director, U.S. Scientific and Medical Affairs, Sanofi Pasteur. "Since two lineages of influenza type B circulate each season, public health officials have been challenged to predict which B virus to include in the vaccine to achieve the greatest effectiveness against circulating influenza strains. Due to increased vaccine production capacity in the U.S. we now have the ability to produce quadrivalent influenza vaccine to help protect against both lineages of B influenza and potentially provide a greater public health benefit from influenza immunization."

The strains for each season's influenza vaccine are selected by the FDA, in consultation with global health authorities, from the strains anticipated to circulate in the approaching influenza season. Seasonal influenza vaccines contained only two strains (one strain of type A influenza and one strain of type B influenza) until 1978, when the decision was made to incorporate a second type A influenza strain in order to provide protection against the two different A strains that were co-circulating. From then until now, influenza vaccines have been trivalent to help protect against three stains of influenza virus (two of type A and one of type B). However, since the influenza B Victoria lineage re-emerged worldwide in 2001-2002, two influenza B strains (one each from the Victoria and Yamagata lineages) have co-circulated with varying prevalence, making it difficult to predict the next season's dominant B strain. In six of the past 12 seasons, the dominant circulating B strain was from the B-lineage not selected for the vaccine, and even in years where the correct B virus strain was selected for the vaccine, some influenza disease was caused by the B strain omitted from the vaccine likely reducing the overall vaccine effectiveness against circulating influenza viruses. Inclusion of both circulating B lineages is a public health measure that can help reduce cases of influenza disease that could be vaccine-preventable if the additional strain were in the vaccine.

Sanofi Pasteur QIV Clinical Development Program
Clinical trials involving 5,592 individuals with 3,307 of these receiving QIV have been conducted to evaluate the safety and immunogenicity of QIV as part of Sanofi Pasteur's development program. These clinical trials included a Phase II study of 570 adults 18 years of age and older, a Phase III study in an elderly population of 675 people 65 years of age and older and a Phase III pediatric study of 4,347 children 6 months through 8 years of age. All three of these randomized, active-controlled, three-arm, multicenter studies were conducted in the U.S., with participants randomized to receive investigational QIV containing strains from both B lineages or trivalent influenza vaccine (TIV). The TIV comparators were the licensed TIV (Fluzone vaccine, containing a Victoria-lineage B strain) or an investigational TIV containing the alternate (Yamagata) B-lineage strain. In each study, all three vaccines contained the same two licensed influenza A strains.

Each study vaccine contained 15 mcg influenza virus antigen per strain per 0.5mL dose (7.5 mcg influenza virus antigen per 0.25 mL dose). Children 6 months through 35 months of age received the 0.25 mL dose whereas children 3 years through 8 years of age and all adults and elderly received the 0.5 mL dose. Children 6 months through 8 years of age received one or two doses administered four weeks apart as recommended by the Advisory Committee on Immunization Practices.

The objectives of the studies included demonstration of non-inferiority of antibody responses to each influenza strain in QIV compared with responses to each respective strain in the TIV comparators. Additional objectives of the Phase III studies were to demonstrate superiority of antibody responses to each B strain in QIV compared with antibody titers following vaccination with the TIV that did not contain the corresponding B strain. Antibody responses were assessed by the amount of antibody produced (geometric mean titers), the proportion of vaccine recipients developing four-fold rises of antibody (seroconversion rates) and the proportion of vaccine recipients producing enough antibody to achieve protective titers (seroprotection rates). Immunogenicity was assessed before and three to four weeks after vaccination. Safety was assessed throughout the duration of each study.

Study Results
In the clinical trials non-inferiority criteria were met for all four strains in QIV compared with the two control TIV formulations in 35 of 36 analyses in adults, elderly and children. Non-inferiority criteria were met separately for children in the sub-groups 6 months through 35 months of age and 3 years through 8 years of age as measured by geometric mean titers (GMTs) and seroconversion rates. Although non-inferiority to A/California (H1N1) was narrowly missed for seroconversion rates in adults 65 years of age and older, non-inferiority was achieved for the GMTs, and seroprotection against this strain was achieved in 91 percent of participants.

QIV induced statistically superior GMTs and seroconversion rates for each B strain in QIV compared with each TIV that did not contain the corresponding B strain in 15 of 16 analyses in children and elderly. In the adults 65 years of age and older, superiority of the GMTs to B/Brisbane (Victoria lineage) was marginally missed; however, superiority of the seroconversion rate and non-inferiority of the GMT and seroconversion rate were achieved for this strain.

The safety profiles of the QIV and the TIV formulations in the studies did not materially differ as assessed by rates of solicited injection-site and systemic reactions, unsolicited adverse events and serious adverse events. Across all three studies the most frequently reported solicited injection-site reaction was pain or tenderness. The most frequently reported systemic reactions were muscle ache (myalgia), headache and feeling unwell (malaise) in older children; and irritability, crying and drowsiness in younger children. Rates of unsolicited adverse events and serious adverse events were similar among the study groups.

Important Safety Information about Fluzone Vaccine
Fluzone vaccine is an inactivated influenza virus vaccine indicated for active immunization of persons 6 months of age and older against influenza disease caused by influenza virus subtypes A and type B contained in the vaccine.

The most common local and systemic adverse reactions to Fluzone vaccine include pain, erythema and swelling at the vaccination site; fever, malaise and myalgia. Other adverse reactions may occur. Fluzone vaccine should not be administered to anyone with a severe allergic reaction (e.g., anaphylaxis) to any vaccine component, including egg protein or thimerosal (the multi-dose vial of Fluzone vaccine is the only presentation that contains thimerosal), or to a previous dose of any influenza vaccine.

The decision to give Fluzone vaccine should be based on the potential benefits and risks, especially if Guillain-Barre syndrome has occurred within 6 weeks of receipt of a prior influenza vaccine. Vaccination with Fluzone vaccine may not protect all individuals.

Before administering Fluzone vaccine, please see the full Prescribing Information available at www.sanofipasteur.us or www.vaccineshoppe.com.

About Sanofi
Sanofi, a global and diversified healthcare leader, discovers, develops and distributes therapeutic solutions focused on patients' needs. Sanofi has core strengths in the field of healthcare with seven growth platforms: diabetes solutions, human vaccines, innovative drugs, consumer healthcare, emerging markets, animal health and the new Genzyme. Sanofi is listed in Paris (EURONEXT: SAN) and in New York (NYSE: SNY).

Sanofi Pasteur, the vaccines division of Sanofi, provides more than 1 billion doses of vaccine each year, making it possible to immunize more than 500 million people across the globe. A world leader in the vaccine industry, Sanofi Pasteur offers the broadest range of vaccines protecting against 20 infectious diseases. The company's heritage, to create vaccines that protect life, dates back more than a century. Sanofi Pasteur is the largest company entirely dedicated to vaccines. Every day, the company invests more than EUR 1 million in research and development. For more information, please visit: www.sanofipasteur.com or www.sanofipasteur.us.

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SOURCE Sanofi Pasteur