Human rhinoviruses are a member of a large family of small viruses known as picornaviruses which are responsible for a wide range of human and animal diseases. There are currently three human rhinovirus (HRV) species: A, B and C, which together with the closely related enterovirus species form the genus enterovirus. These are responsible for human diseases ranging from mild respiratory tract infections (the common cold) to paralytic poliomyelitis. HRV are the most commonly isolated viruses from people with mild upper respiratory tract illness. In otherwise healthy adults this manifests as several minor symptoms such as a runny or blocked nose, sneezing, a sore throat, a dry cough, red eyes and a general feeling of tiredness. These people generally recover within a week but in some cases symptoms persist for longer periods.
HRV can be a much more serious problem for some segments of the population such as infants and the frail elderly. For example, in the United States, 75% of common colds in children under five years are medically attended and HRV has been linked with roughly one third of children with middle ear infections (acute otitis media). HRV is the second most frequently recognized infection associated with pneumonia and bronchiolitis in infants. There is also growing evidence for HRV as the causative agent for severe lower respiratory tract illness in older adults and in highly immunocompromised people, such as bone marrow transplant recipients. These diseases can be fatal.
HRV is a major cause of hospitalisation for patients with underlying respiratory conditions, such as asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis, where HRV can aggravate their existing disease. Estimates suggest that HRV is linked to about 70% of all asthma exacerbations and more than 50% of the hospitalised cases. Studies also suggest that more than 35% of acute COPD patients requiring hospitalisation, are associated with respiratory viruses, including rhinovirus.
There is currently no effective treatment for HRV. Therefore, if successful, Biota's HRV antiviral will address an important and unmet medical need.
Rhinoviruses access respiratory tract cells by attaching to a receptor on the cell surface. Canyon-like clefts on the surface, or capsid, of the virus attach to the receptor which precedes virus infection of the cell. Biota is developing antiviral compounds which are designed to bind to a highly conserved pocket in the floor of the canyon. These "capsid binders" effectively stop infection by interfering with receptor binding and/or related early steps in the infectious cycle. Biota's lead capsid binder, vapendavir or BTA798, is a broad spectrum inhibitor of the large group of culturable HRVs with compelling activity for a variety of diverse enteroviruses (such as poliovirus). It is designed to be dosed orally.
Biota completed a Phase I (single & multi-dose) clinical trial of vapendavir in 2007. A Phase IIa (challenge study) in 2009 achieved clinical proof-of-concept, demonstrating that oral BTA798 significantly reduces the incidence of infection and reduces viral shedding in volunteers experimentally infected with HRV. A Phase IIb study in asthmatics with naturally acquired HRV infection successfully achieved the Primary Endpoint in March 2012.