GAITHERSBURG, Maryland, August 23 /PRNewswire/ --
MedImmune, Inc. today announced that in a Phase 3 study, motavizumab was shown to reduce hospitalizations due to respiratory syncytial virus (RSV) by 83 percent as compared to placebo (8.3 percent in placebo arm vs. 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.
Motavizumab is an investigational monoclonal antibody (MAb) being evaluated for its potential to prevent serious disease caused by RSV in high-risk pediatric patients. This Phase 3 trial involved 1,410 full-term infants less than six months of age in two Native American populations. In previous medical studies these populations were shown to have high rates of hospitalization due to RSV.
The randomized (2:1), double-blind study was designed to compare monthly intramuscular injections of motavizumab against placebo. After an interim analysis conducted by an independent data safety monitoring committee, the study was unblinded early due to statistical evidence demonstrating that motavizumab reduced RSV hospitalizations and LRIs requiring outpatient medical management within this population. Kate O'Brien, M.D., associate professor at the Center for American Indian Health, Johns Hopkins Bloomberg School of Public Health, served as the study's principal investigator.
"We are pleased with the results of this study which support the positive results seen in our Phase 3 pivotal trial comparing motavizumab and Synagis(R) (palivizumab) that were previously reported at the Pediatric Academic Societies meeting in May 2007," said Genevieve Losonsky, M.D., vice president, clinical development, infectious disease, MedImmune.
Motavizumab was well tolerated in these Native American infants, with an overall incidence and severity of adverse events (AEs) that were similar between the motavizumab and the placebo groups. 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 hypersensitivity related skin rashes within two days of dosing were seen in about one percent of treated children in the motavizumab group.
MedImmune's Commitment to RSV Prevention
MedImmune is a world leader in the development of innovative therapeutic biologic products to prevent RSV disease. In 1996, MedImmune launched the first anti-RSV drug, RespiGam(R) (respiratory syncytial virus immune globulin intravenous (human) (RSV-IGIV)), which was a polyclonal antibody administered via four-hour intravenous infusion. In 1998, MedImmune introduced Synagis, which was a significant product improvement as a monthly intramuscular injection for the prevention of severe RSV, as well as being the first MAb to receive U.S. Food and Drug Administration (FDA) approval for an infectious disease. With the development of motavizumab, MedImmune continues to reinforce its commitment to developing anti-RSV products. In a head-to-head comparative Phase 3 trial with Synagis, motavizumab met its primary endpoint of reducing RSV-related hospitalizations in high-risk pediatric patients and met its secondary endpoint of reducing medically attended, outpatient respiratory tract infections in that patient group. MedImmune is also developing a small-molecule product candidate to prevent RSV as well as a vaccine against RSV, both of which are in Phase 1 clinical trials.
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).
Motavizumab, formerly known as Numax(R), 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 and Phase 2 study data have been reported showing that motavizumab appears to have a similar safety and pharmacokinetic profile to Synagis in infants. Additionally, in early phase studies children treated with motavizumab had reduced RSV replication in the upper respiratory tract. In its first pivotal trial, which was a head-to-head comparative trial with Synagis, motavizumab demonstrated a 26-percent reduction in RSV hospitalizations due to RSV and a 50-percent reduction in the incidence of RSV lower respiratory tract infections requiring outpatient management, its secondary endpoint.
Synagis is the only monoclonal antibody approved by the FDA to help prevent an infectious disease. Synagis was approved for use in the United States in 1998, Europe in 1999, and Japan in 2002. Synagis is currently available in 62 countries.
Synagis is indicated for the prevention of serious lower respiratory tract disease caused by respiratory syncytial virus (RSV) in pediatric patients at high risk of RSV disease and is administered by intramuscular injection. The safety and efficacy of Synagis were established in infants with bronchopulmonary dysplasia (BPD), infants with a history of prematurity (less than or equal to 35 weeks gestational age), and children with hemodynamically significant congenital heart disease. The first dose of Synagis should be administered prior to commencement of the RSV season, which usually starts in the fall and runs through the spring. Patients, including those who develop an RSV infection, should continue to receive monthly doses throughout the season.
Very rare cases (<1 per 100,000 patients) of anaphylaxis and rare (<1 per 1,000 patients) hypersensitivity reactions have been reported with Synagis. Cases of anaphylaxis were reported following re-exposure to Synagis and rare severe hypersensitivity reactions occurred on initial exposure or re-exposure. If a severe hypersensitivity reaction occurs, therapy with Synagis should be permanently discontinued. If milder hypersensitivity reaction occurs, caution should be used on re-administration of Synagis.
In clinical trials, the most common adverse events occurring at least one percent more frequently in Synagis-treated patients than controls were upper respiratory infection, otitis media, fever and rhinitis. Cyanosis and arrhythmia were seen in children with CHD.
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: http://www.medimmune.com/products/synagis/index.asp.
About International RSV Prophylaxis
Outside the United States, Synagis is distributed by Illinois-based Abbott, a global, broad-based health care company. Abbott also has the ex-U.S. distribution rights to motavizumab.
About MedImmune, Inc.
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 the areas of infectious diseases, cancer and inflammatory diseases. 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 http://www.medimmune.com.
Web site: http://www.medimmune.com
Media - Tor Constantino, +1-301-398-5801, or Investors - Peter Vozzo, +1-301-398-4358, both of MedImmune, Inc.