ALS-008176 now being evaluated in RSV-infected infants
Alios BioPharma, Inc., part of the Janssen Pharmaceutical Companies announced that the New England Journal of Medicine (NEJM) will publish findings from a respiratory syncytial virus (RSV) challenge study for ALS-008176, a cytidine nucleoside analog with activity against RSV. Among infants and young children, RSV is the leading cause of severe respiratory illness and remains the most frequent cause of hospitalization in industrialized countries. This Phase 2a study has now established human proof-of-concept for the antiviral activity of ALS-008176 in healthy adults and highlights its potential as a therapy for managing clinical disease in naturally infected patients.
“The data suggest that ALS-008176 has the potential to be a safe and effective treatment for RSV infection. The primary endpoint of the study was met and ALS-008176 significantly reduced viral load and symptoms of disease severity compared to placebo,” said John DeVincenzo, M.D., the lead study author and Professor of Pediatrics, and Professor of Microbiology, Immunology and Biochemistry at the University of Tennessee Health Science Center, and Medical Director of Molecular and Viral Diagnostics at Le Bonheur Children's Hospital. “ALS-008176 can inhibit the replication of RSV even if the cells of the respiratory tract have already been infected with the virus. As a result, this treatment has an antiviral effect and is likely to be effective even if started at a later stage of RSV infection.”
In this randomized, double-blind study, 62 healthy volunteers were inoculated with RSV and subsequently randomized to receive ALS-008176 or placebo. Compared to placebo, treatment with ALS-00876 resulted in a significant reduction of viral load (73-88% reduction in viral load area under the curve) and faster viral clearance (1.3–2.3 days vs 7.2 days) versus placebo. At the time that the peak viral load occurred in the placebo group, the mean viral load in each of the three ALS-007186 treatment groups was more than one thousand times lower. In addition, statistically significant reductions in symptom scores and a reduction of the amount of congesting respiratory secretions were also observed.
In the study, no serious adverse events (SAEs), premature discontinuations of study drug, or clinically significant treatment related adverse events (AEs) were observed. The most commonly reported AEs were epistaxis (bleeding from the nose), upper respiratory infection and cough. AEs were generally balanced in terms of frequency and intensity across recipients of ALS-008176 and placebo. ALS-008176 also demonstrated a high barrier to resistance. No participants receiving ALS-008176 experienced viral rebound or had evidence of viral resistance during the course of the study.
RSV is a seasonal virus that affects the lungs and airways for which there is currently no vaccine and no guideline-recommended antiviral treatment options available. RSV can be partially prevented by a monoclonal antibody, but its use is limited to a small fraction of premature infants or infants with uncommon heart or lung problems. Each year, there are approximately 64 million cases of RSV infection among adults and children and nearly 100% of infants will have at least one RSV infection by their second year of life. In a single year (2005), around 33.8 million infants and young children had RSV infections in the lower respiratory tract and at least 3.4 million were hospitalized. This was associated with between 66,000 and 199,000 deaths.
“Janssen is currently working on the discovery and development of multiple treatment and vaccine candidates against RSV infection,” said Lawrence M. Blatt, PhD, Global Therapeutic Area Head Infectious Diseases and Vaccines, Janssen Research & Development, LLC. “The data published in the New England Journal of Medicine highlight the potential this new compound has to effectively treat patients suffering from severe RSV infection. It underscores our commitment to develop highly innovative healthcare solutions in areas of great unmet need.”
ALS-008176 is an orally bioavailable prodrug of the RSV replication inhibitor ALS-008112, a cytidine nucleoside analog. It is designed to inhibit the replication of RSV by acting on the viral polymerase and is currently being evaluated in hospitalized RSV-infected infants.