Delivery of RNAi Therapeutics to the Airways—From Bench to Bedside

Qiu, Yingshan; Lam, Jenny K. W.; Leung, Susan W. S.; Liang, Wanling

The phase I clinical study of ALN-RSV01 was reported in 2008 [139] . Intranasal administration of ALN-RSV01 was well tolerated and the side effect profile was similar to placebo. Later in 2010, the antiviral effect of ALN-RSV01 was evaluated in a phase II trial. ALN-RSV01 was administered by nasal spray daily to healthy adults for two days before and for three days after RSV inoculation. The group treated with ALN-RSV01 had a significantly lower number of RSV infection compared to the placebo group [140] . Another phase II b clinical trial of ALN-RSV01 in RSV-infected lung transplant patients was also completed [141] . The primary endpoint of the study was to evaluate the effect of ALN-RSV01 on the incidence of new or progressive bronchiolitis obliterans syndrome (BOS) in RSV-infected lung transplant patients. Even though the study marginally missed the primary endpoint statistically (p = 0.058), inhaled ALN-RSV01 treatment induced a clinically meaningful reduction in the incidence of BOS, reinforcing the potential of inhaled RNAi as new antiviral therapeutics.