Aventis Submits Application for FDA Approval of Menactra, First Candidate Quadrivalent Conjugate Meningococcal Vaccine

SWIFTWATER, Pa. -- Aventis announced today the submission of a Biologics Licensing Application (BLA) to the U.S. Food and Drug Administration (FDA) for marketing approval of the use of Menactra Meningococcal (Groups A, C, Y and W-135) Polysaccharide Diphtheria Toxoid Conjugate Vaccine for protection against meningococcal meningitis in adolescents and adults aged 11-55 years. This will be the first electronic BLA filing for Aventis Pasteur.

A submission for ages 2-55 is planned for 2004 in Europe and submissions for groups below 11 years of age will follow in the U.S.

Menactra vaccine is the first quadrivalent conjugate candidate for the prevention of meningococcal meningitis, considered the most deadly form of the three main types of meningitis. This vaccine is designed to offer protection against four serogroups of meningococcal disease (A, C, Y, W-135).

This submission of this novel vaccine by Aventis Pasteur, the vaccines business of Aventis, is the third new product submission by Aventis in 2003. In June, the fast-acting insulin Apidra was submitted for approval in the EU and the U.S. In December, Genta and Aventis submitted to the FDA the targeted cancer therapy Genasense for fast-track approval. Aventis is planning to submit the asthma medicine Alvesco, which is developed in co-operation with Altana Pharma, to the FDA by the end of 2003.

"With this third submission, we are on track to achieve our goal of submitting four new products for approval in 2003," said Igor Landau, chairman of the management board of Aventis. "The various new products should complement our portfolio in key disease areas -- mainly diabetes, cancer and vaccines -- and are expected to substantially contribute to our growth in the coming years."

"We are extremely pleased that our efforts to develop a conjugate vaccine for meningococcal disease have resulted in filing a BLA with the FDA," said Michel DeWilde, executive vice president of research and development for Aventis Pasteur. "Conjugate vaccines have been shown to induce a better and longer-lasting immune response than polysaccharide vaccines, we believe Menactra vaccine offers the potential for substantial control of bacterial meningitis."

The regulatory submission is based on results of six pivotal studies, involving more than 7,500 clinical trial participants that received Menactra vaccine (also called MCV-4). The vaccine has shown an excellent safety and immunogenicity profile.

Aventis Pasteur is currently constructing a new, state-of-the-art production facility at its U.S. site in Swiftwater, Pa., to produce Menactra meningococcal vaccine. The new facility is intended to ensure Aventis Pasteur's ability to meet anticipated global demand for the product.

Meningococcal disease is a rare but devastating bacterial infection and the leading cause of bacterial meningitis, which strikes between 2,500 and 3,000 Americans -- mostly children and adolescents -- every year, killing up to one in five of those infected. Of survivors, up to one in five suffer long-term permanent disabilities such as hearing loss, brain damage, and limb amputations. Although the disease is most common in children under age four, in the 1990s, incidence increased substantially among 15- to 24- year-olds, and one study found a 22.5 percent fatality rate among people in this age group who contracted meningococcal disease.

The current FDA-licensed meningococcal disease vaccine, Menomune(R) -A/C/Y/W-135 (Meningococcal Polysaccharide Vaccine, Groups A, C, Y and W-135 Combined), is made from a long chain of polysaccharides that come from the outer coat of the meningococcus bacterium, providing a limited duration of immunity. Duration of protection against meningococcal disease with Menomune A/C/Y/W-135 lasts approximately three to five years.

Menactra vaccine is a conjugate vaccine, created by attaching the meningococcal polysaccharides to a carrier protein. Historically, conjugate vaccines have been shown to induce boostable memory responses and longer-lasting immune responses than polysaccharide vaccines. Since 1990, vaccines employing conjugate technology have substantially reduced two other bacterial infections that were major causes of bacterial meningitis in young children: Haemophilus influenzae type b and Streptococcus pneumoniae.

Experience in the United Kingdom (U.K.) suggests that conjugate vaccines may provide significant benefits over traditional vaccines. From 1999 to 2000, the U.K. ran a national campaign to immunize 15 million children under age 17 with a conjugate vaccine that offered protection against one serogroup (the C serogroup) of meningococcal bacteria. The campaign resulted in an 85 percent overall decline in cases and 90 percent reduction in deaths from meningococcal serogroup C disease one year later.

Disease rates declined among unvaccinated children as well as among those who were vaccinated, suggesting that the vaccine suppressed transmission of the infection in the unvaccinated population, thus offering the public health benefits of herd immunity.

Obtaining similar public health benefits in the U.S. would require a vaccine that protects against multiple serogroups of meningococcal bacteria. Four serogroups of the bacteria (C, Y, W-135, and B) predominate in the U.S. Menactra vaccine contains three of these four serogroups, which cause approximately two-thirds of meningococcal disease overall and 79 percent in the adolescent population. In the U.K., by contrast, two serogroups (C and B) predominate; the C serogroup caused 38 percent of meningococcal disease in that country prior to vaccination. There is no vaccine against meningococcal disease caused by the B serogroup.

Source: Aventis