MedImmune, Inc. has announced preliminary results from a phase 3 pivotal study showing that Numax met its primary endpoint of non-inferiority by reducing the incidence of hospitalizations caused by respiratory syncytial virus (RSV) in infants at high risk for serious RSV disease by 26 per cent when compared to Synagis (palivizumab). The data also indicate that Numax showed superiority over Synagis in a secondary endpoint by reducing the incidence of RSV-specific medically attended outpatient lower respiratory infections (LRI) by approximately 52 per cent.

"We are very pleased with the outcome of this large, multi-national phase 3 study comparing Numax to Synagis, which is the current standard of care in the US for preventing RSV in high-risk infants," said Edward M. Connor, M.D., chief medical officer and executive vice president. "The preliminary results of this study are highly encouraging and indicate that Numax may have the potential to offer high-risk infants additional protection against RSV infection over and above Synagis, which has an established safety and efficacy profile. We intend to continue to evaluate the complete data set to more fully understand the trial results, and then to review the data with the U.S. Food and Drug Administration."

The pivotal phase 3 study was designed to compare the safety and efficacy of Numax with that of Synagis in infants at high risk for serious RSV disease for the reduction of serious RSV disease in the inpatient and outpatient settings. The primary endpoint was to assess the non-inferiority of Numax compared to Synagis in the incidence of hospitalizations caused by RSV. By design, non-inferiority was defined to have been demonstrated if the upper bound of the two-sided 95 per cent confidence interval of the relative risk (RR) for the primary endpoint was lower than 1.265. As indicated above, Numax showed a 26-per cent reduction in RSV hospitalizations compared to Synagis. The corresponding p-value for non- inferiority analysis was 0.01. In the trial, the overall RSV attack rate was 1.4 per cent for infants receiving Numax compared to 1.9 per cent for those who received Synagis. The study's RSV-related secondary efficacy endpoint, conducted in a subset of sites, was the comparative reduction of RSV-specific medically attended outpatient LRI. Numax showed a 52-per cent statistically superior reduction in RSV-specific medically attended LRIs compared to Synagis; the overall RSVspecific medically attended LRI rate was 1.9 per cent for infants receiving Numax compared to 3.9 per cent for those who received Synagis.

"The conduct of this trial by study investigators was outstanding," commented Genevieve Losonsky, M.D., vice president, clinical development, infectious disease. "The trial's success is a testimony to the quality of their work, as well as to the commitment of their staff and to the parents. on the part of their children who participated in the study."

In this preliminary assessment, the number and type of adverse events and serious adverse events were balanced between the study groups. The overall mortality rates were comparable between the two groups (0.1 percent Synagis and 0.2 percent Numax). Study drug was discontinued due to related adverse events in a small number of children in each group (0.1 percent Synagis and 0.3 percent Numax). Immunogenicity in the Numax arm was low, less than 1 percent, and comparable to the historical Synagis rate.

The trial was a randomized, double-blind study involving approximately 6,600 high-risk infants at more than 300 centers in 24 countries within the Northern and Southern Hemispheres conducted over two years during multiple RSV seasons. Study participants consisted of premature infants born at 35 weeks gestational age or less who were six months of age or younger at randomization, as well as children with chronic lung disease related to prematurity (CLD) requiring medical management within the six months prior to study entry, who were 24 months of age or less at randomization.

Each year, an estimated 125,000 infants in the US are hospitalized with severe RSV infections, the leading cause of infant hospitalization in the US (1) RSV is the most common respiratory infection in infancy or childhood. Approximately one-half of all infants are infected with RSV during the first year of life, and nearly all children have been infected at least once by the time they reach their second birthday. Children born prematurely as well as those with chronic lung disease or congenital heart disease are at highest risk for severe disease and hospitalization due to RSV. The virus may also cause severe illness in other high-risk groups such as the elderly, those with underlying respiratory or cardiac disease, and those with compromised immune systems (e.g., bone marrow transplant patients).

Numax is an investigational humanized monoclonal antibody being evaluated for its potential to prevent serious lower respiratory tract disease caused by RSV in pediatric patients at high risk of RSV disease. phase 1 and phase 2 studies have been reported showing that Numax appears to have a similar safety and pharmacokinetic profile to Synagis in infants. Additionally, in early phase studies children treated with Numax had reduced RSV replication in the upper respiratory tract.

Synagis is the only monoclonal antibody approved by the US Food and Drug Administration to help prevent an infectious disease. Since its licensure in 1998, Synagis has been administered to more than 800,000 infants in the US and has become the standard of care for infants at high risk for RSV. Synagis is indicated for the prevention of serious lower respiratory tract disease caused by RSV in pediatric patients at high risk of RSV disease, which is prominent in the Northern Hemisphere during the winter months. Synagis is a humanized monoclonal antibody given by an intramuscular injection once a month during the RSV season. Synagis was approved in 1998 by the FDA; in 1999, by the European medicines evaluation agency; and in 2002, by the Japanese ministry of health, Labor and Welfare. In 2003, the FDA expanded the US label for Synagis for use in young children with hemodynamically significant congenital heart disease at risk of RSV disease. To date, Synagis has been approved in 62 countries, including the US. In clinical trials, the most common adverse events occurring at least 1 percent more frequently in Synagis-treated patients were upper respiratory infection, otitis media, fever and rhinitis. Cynanosis and arrhythmia were seen in children with CHD. Very rare cases of anaphylaxis (less than 1 case per 100,000 patients) and rare hypersensitivity reactions have been reported. Synagis should not be used in patients with a history of a severe prior reaction to Synagis or its components.