MIV-323 for the treatment of RSV infection
Respiratory syncytial virus (RSV) is a respiratory pathogen that can cause life-threatening infections, especially in children. Treatment of RSV infection represents a large unmet medical need. The RSV project resulted from a 2014 licensing agreement with Boehringer Ingelheim International GmbH for exclusive, global rights to a drug programme for the treatment and prevention of RSV.
Mechanism of Action
MIV-323 is a small molecule inhibitor of the RSV Fusion (F) protein that is suitable for oral administration. The RSV F protein is an essential virus-encoded protein required for the virus to enter cells of the respiratory tract, and is a clinically- validated RSV target. Inhibiting the activity of the F protein will result in reduction of the severity and incidence of RSV- associated disease caused by RSV infections of the human upper and lower respiratory tract.
RSV infects the lungs and the upper airways and can cause bronchiolitis and pneumonia. In healthy adults, RSV infection is usually restricted to the upper respiratory tract causing disease that is often limited to mild cold-like symptoms lasting up to two weeks. However, elderly patients, especially those with chronic heart or lung conditions, and patients who are immunocompromised e.g. those who have undergone transplantations, are at increased risk for severe RSV-associated disease. Further, RSV infection accounts for substantial morbidity and mortality among infants and is a common reason for them being hospitalised, with an even greater outpatient burden of disease. It is estimated that RSV accounts for 64 million total infections per year (WHO data). Among children below the age of 5 there are 33.8 million lower respiratory tract infections reported for 2005, with 3.4 million of those requiring hospitalization. These are estimated to have caused between 66,000 and 199,000 child deaths.
The risk of death from respiratory causes in infants below 1 year of age is increased 9-fold for infants who have RSV infection as opposed to those that have influenza. Furthermore, severe RSV infection in early childhood is also associated with recurrent wheezing later in life. Inhaled ribavirin is the only approved treatment for RSV infection, but is of questionable benefit and is extremely difficult to administer. Palivizumab is an RSV-specific monoclonal antibody that is approved for the prevention of RSV infection, but it is only partially effective and is indicated only for the 3% of infants that are born prematurely or have underlying severe chronic illnesses. Given that the standard of care for the vast majority of RSV-infected patients is limited to supportive therapy only, a large unmet medical need exists for therapies that both prevent and treat RSV infections in both elderly as well as pediatric patients. Clinical evaluations of experimental drugs for RSV have reached phase II, but to date the only efficacy data have come from healthy human adults who have been experimentally infected with RSV.
Medivir’s RSV fusion protein inhibitor project was in-licensed in August 2014 in the discovery phase. Medivir scientists have systematically optimized the properties of these early molecules, resulting in the selection of MIV-323 as a candidate drug in late 2016. MIV-323 is currently in non-clinical development and the overall aim for the project is to find a partner for the clinical development and marketing of the project.