RSV drug clears Phase I
to immunocompromised patients - has completed Phase I trials,
raising hopes of the first effective treatment for the virus,
writes Wai Lang Chu.
The compound, called A-60444, has been developed by UK-based Arrow Therapeutics and has been shown to be safe and well tolerated in a once daily, oral dosing regimen.
The trial was carried out on a mixed group of healthy volunteers in the UK. The volunteers all received a dose of the virus and were then treated with the compound. Efficacy levels in the assay were found to be high, and the drug is set to move into Phase II trials in September.
At present, the only drugs approved for RSV are Medimmune's monoclonal antibody Synagis (palivizumab), indicated for the prevention of RSV in premature infants, who are particularly vulnerable to the infection, and the company's older, polyclonal antibody-based RespiGam.
Margaret Walsh, head of business development at Arrow Therapeutics told DrugResearcher.com: "There was a need for a new treatment. Existing therapies such as Synagis are extremely expensive costing up to $5,000 (€4100) per course of treatment."
"The compound inhibits copying of the virus by stopping the production of one of the proteins central to replication."
RSV is one of the most common viral pathogens. Nearly all children have been infected by the age of two years. Infection with RSV typically results in symptoms associated with a common cold. However, RSV may be a significant cause of morbidity and mortality in a range of patient groups.
Infants under 2 years are particularly at risk with 2 per cent are hospitalised each year. In the US this represents an estimated 125000 paediatric hospitalisations. Elderly adults with chronic obstructive pulmonary disease (COPD) and congestive heart failure are thought to be at risk as well as immuno-compromised individuals.
Walsh said: "We are hoping that this new compound is effective for all patient groups at risk. With these groups, the main problem is diagnosing the disorder which can be difficult considering the additional ailments they are suffering from."
"The emphasis at the moment is to develop this compound into an effective form of treatment against RSV. If all goes well, we would consider later developing the compound into a prophylactic."
The recommended dose of Synagis is 15 mg/kg of body weight, given once a month during RSV season (October to May, but significant regional variation exists). This treatment is not appropriate for other patients however, due in part to its high cost and low potency.
Arrow plans to partner the RSV project after clinical proof of concept. Walsh added there was considerable interest from parties who wanted to develop the compound from a respiratory disease and COPD approach. There was hope a partnership would be in place by the first quarter of 2005.
"The extent of the RSV problem in the UK mirrors that of the US. It is a virus that is extremely contagious and can result in hospital wards being shut down," she said.
Asthma link?
In related news, a study published in The Journal of Infectious Diseases is the first to show a link between RSV, infection and asthma in mice.
Researchers at UT Southwestern Medical Centre at Dallas infected healthy mice with RSV and monitored the animals for 154 days. The infected mice developed pneumonia as well as chronic lung problems. The RSV-infected group developed airway obstruction, mucus overproduction and airway hyper-responsiveness, or asthma, while a control group did not.
Dr Octavio Ramilo, associate professor of paediatrics in the Cancer Immunobiology Centre and the study's senior author said: "We have suspected a connection between asthma and RSV for a long time, but there has been no scientific evidence confirming this theory until now,"
"RSV is a very common virus and one of the most frequent respiratory illnesses. Most babies will get over the infection, but some develop severe wheezing and other permanent asthma-like symptoms."
