Respiratory syncytial virus – ALN-RSV-01
RSV is the most common cause of child hospitalisation in the developed world and the effectiveness of existing drugs is limited
Respiratory syncytial virus, or RSV, is the most common cause of child hospitalisation in the developed world, and is also a big problem in both the elderly and adults with compromised immune systems. Although vaccines are in development, as yet none is on the market, and the effectiveness of existing drugs is limited. US biotech Alnylam is taking another tack – it is developing an RNAi-based drug to attack the virus.
The drug, ALN-RSV-01, is a short interfering RNA, or siRNA, that targets the nucleocapsid N gene of the RSV genome, thus preventing the synthesis of the viral nucleocapsid protein and interfering with the virus’s replication process.1 In two single and multiple dose, randomised, dose escalation, observer blinded safety and tolerability studies, 101 healthy adults were given the drug or placebo.2
The drug was given intranasally and was well tolerated over a dose range up to 150mg, and as both single doses and in five daily doses. Adverse events were comparable between the group given the active and those given saline as placebo, and these were transient and mild to moderate, and showed no dose dependency. Increasing exposure to the drug had no effect on adverse events, either. The bioavailability of the drug was minimal, and it appeared both safe and well tolerated.
A randomised, double blind, placebo-controlled Phase II trial has also been carried out.3 A total of 88 patients were given the siRNA or saline placebo intranasally for two days before, and then for three days after, inoculation with RSV. The virus was measured using nasal washes. The drug was well tolerated and again the safety profile was similar to saline. The proportion of viral infections, as defined by culture, was 44% in those given the drug and 71% in placebo, and the acquisition of infection was significantly lower in the siRNA group compared with the placebo group.
Earlier this year, the company started a Phase IIb trial in adult lung transplant patients naturally infected with RSV, which is a significant cause of morbidity in this patient group. This trial follows on from a Phase IIa study in RSV-24 infected lung transplant patients, which showed the drug was safe and well tolerated, and gave improved recovery of lung function after 90 days.
references
1. R. Alvarez et al. Antimicrob. Ag. Chemother. 2009, 53, 3952
2. J. DeVincenzo et al. Antiviral Res. 2008, 77, 225
3. J. DeVincenzo et al. Proc. Nat. Acad. Sci. USA 2010, 107, 8800