HONOLULU, HI, May 4, 2008 - MedImmune today announced that researchers are currently presenting results from a MedImmune-sponsored Phase 3 study involving motavizumab, an investigational monoclonal antibody (MAb) that is being evaluated for its potential to prevent serious disease caused by respiratory syncytial virus (RSV) in high-risk pediatric patients. Kate O'Brien, M.D., M.P.H., associate professor at the Center for American Indian Health, Johns Hopkins Bloomberg School of Public Health, is the study's principal investigator. Aruna Chandran, M.D., M.P.H., a trial co-investigator, presents the data today at the Pediatric Academic Societies (PAS) Annual Meeting in Honolulu, HI.
This randomized Phase 3 study demonstrated that motavizumab reduced hospitalizations due to RSV by 83 percent as compared to placebo (8.3 percent in placebo arm versus 1.4 percent in motavizumab; p<0.001), as the trial's primary endpoint. In addition, the trial showed a 71-percent reduction in the incidence of RSV-specific lower respiratory infections (LRIs) requiring outpatient management (9.5 percent in placebo group and 2.8 percent in the motavizumab group; p<0.001), which was a secondary endpoint.
The randomized, double-blind Phase 3 study involving 1,410 full-term healthy infants less than six months of age in some Southwest Native American populations was designed to compare monthly intramuscular injections of motavizumab against placebo. In previous epidemiologic studies these populations were shown to have high rates of hospitalization due to RSV. This study confirmed the high rates of serious RSV disease in this population. An interim analysis, reviewed by an independent data safety monitoring committee, concluded there was statistical evidence demonstrating that motavizumab reduced RSV hospitalizations and LRIs requiring outpatient medical management within this population.
The overall incidence and severity of adverse events (AEs) were similar between the motavizumab and the placebo groups in these Native American infants. The mortality rates were not statistically different between groups (0.4 percent in the placebo arm, n=2 and 0.3 percent in the motavizumab arm, n=3) and were not considered to be related to the study drug. As was suggested in the pivotal Phase 3 trial conducted in high-risk, preterm infants, rates of skin reactions were more common following motavizumab than placebo (by an approximately 2 percent increase in frequency). Motavizumab was otherwise well tolerated.
Each year, up to 125,000 infants in the U.S. are hospitalized with severe RSV infections, the leading cause of lower respiratory tract infections in infants in the United States. 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 (CLD) or congenital heart disease (CHD) 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). Otherwise healthy infants in some Native American populations have demonstrated rates of RSV hospitalization that are similar to those among children with underlying medical conditions in the general U.S. population.
Motavizumab is an investigational humanized MAb 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, 2 and 3 study data have been reported showing that motavizumab appears to have a similar safety and pharmacokinetic profile to Synagis® (palivizumab) in infants. Additionally, in early phase studies children treated with motavizumab had reduced RSV replication in the upper respiratory tract. In its pivotal clinical trial, which was a head-to-head comparative trial with Synagis, motavizumab demonstrated non-inferiority with a 26-percent relative reduction in RSV hospitalizations due to RSV, which was its primary endpoint, and a 50-percent relative reduction in the incidence of RSV lower respiratory tract infections requiring outpatient management, one of its secondary endpoints. Rates of adverse events, serious adverse events and study drug discontinuations were balanced between treatment groups.
Synagis (palivizumab) is indicated for the prevention of serious lung infections caused by respiratory syncytial virus (RSV) in children at high risk of RSV disease. Synagis is given as a shot, usually in the thigh muscle, each month during the RSV season. The first dose of Synagis should be given before RSV season begins. Children who develop an RSV infection while receiving Synagis should continue the monthly dosing schedule throughout the season. Synagis has been used in more than one million children in the U.S. since its introduction in 1998.
Synagis is not currently recommended as a preventive measure among Native American infants at high risk for serious RSV disease.
Very rare cases (<1 per 100,000 patients) of severe allergic reactions such as anaphylaxis and rare (<1 per 1,000 patients) hypersensitivity reactions have been reported with Synagis. These rare reactions may occur when any dose of Synagis is given, not just the first one. Also, rare but serious side effects can occur, which may lead to unusual bruising and/or groups of pinpoint red spots found on the skin.
Other side effects with Synagis may include upper respiratory tract infection, ear infection, fever, and runny nose. In children born with heart problems, Synagis was associated with reports of low blood oxygen levels and abnormal heart rhythms. Synagis should not be used in patients with a history of a severe prior reaction to Synagis or its components. Side effects, such as skin reactions around the area where the shot was given (like redness, swelling, warmth, or discomfort) can also occur.
The pivotal trial for Synagis was called the IMpact trial and comprised a total of 1,502 children who were randomized (500 placebo, 1,002 Synagis) in a double-blind, placebo-controlled protocol where 1,486 children completed the study's follow-up.
In the IMpact trial, monthly prophylaxis with Synagis via intramuscular injections was associated with a 55-percent reduction in hospitalization as a result of RSV (p=<0.001). Reductions were observed in both children with bronchopulmonary dysplasia (38 percent reduction) and premature children without BPD (78 percent reduction). Approximately 50 percent of the children in the analysis had BPD.
For full prescribing information for Synagis, see the company's website at: www.medimmune.com/products/synagis/index.asp.
MedImmune strives to provide better medicines to patients, new medical options for physicians and rewarding careers to employees. Dedicated to advancing science and medicine to help people live better lives, the company is focused on infection, oncology, respiratory disease and inflammation, cardiovascular/gastrointestinal disease, and neuroscience. With approximately 3,000 employees worldwide and headquarters in Maryland, MedImmune is wholly owned by AstraZeneca plc (LSE: AZN.L, NYSE: AZN). For more information, visit MedImmune's website at www.medimmune.com.