Alnylam Stakes Claim to 1st Human Demo of Activity for RNAi Therapy

Alnylam (ALNY) has presented top-line results from its Phase 2 POC study of anti-RSV RNAi therapy, known as ALN-RSV01, demonstrating an effect of the therapy in experimental upper respiratory RSV infection.

The intent of this study was to determine whether relatively high doses of ALNRSV-01 delivered intranasally to experimentally infected healthy volunteers could reduce local viral load. The volunteers were given two doses of the drug (one per day) prior to being nasally inoculated with roughly 10,000 viral particles (much higher than the typical natural infection load). Then they were given further treatments of ALN-RSV01 or a matching placebo for an additional three days after inoculation; all told volunteers were quarantined for 12 days (yikes). In order to ensure a reasonable rate of infection, potential volunteers were screened for anti-RSV antibodies. Those with clinically relevant titers of antibodies were excluded from the study, necessitating the screening of 1,000 people to enroll 88 (double yikes).

The rate of infection (primary endpoint, by plaque assay), viral load measures, and clinical symptoms were assessed. In a nutshell, the therapy reduced the rate of viral infection by a number of measures and the primary endpoint was met. Trends were seen in viral load measures but not in symptoms, which were modest in any case.

This was a robust demonstration that RNAi delivered locally (and prophylactically) can reduce (but not eliminate) viral infection. In that respect, it is valuable as a proof of concept in humans for topically delivered RNAi acting against viral cells directly at the site of inoculation. I don’t think it should be construed as a proper POC of systemically delivered RNAi under any circumstances, nor for topically delivered RNAi directed against endogenous gene expression. So, RNAi is still in its infancy, clinically speaking, but it’s showing signs of life.

Investors on the conference call were interested in what this study might mean for the future of this particular therapy. I think Alnylam’s management were appropriately circumspect when addressing the issue. If I were an investor (I’m not), I’d be relieved that this important first hurdle has been cleared, but I’d also have to admit to myself that this therapy is still a long way from proving itself in naturally infected kids and fragile adults with RSV pneumonia.

Alnylam mentioned that the next Phase 2 will be a study of adults with naturally occurring RSV infection, presumably upper respiratory infection. In that setting, ALN-RSV01 won’t be given a headstart over the virus–treatment won’t begin until clinical symptoms have appeared–and effects on symptoms would be helpful to guide future studies and gain investor confidence. So, like any other drug, we’ll have to see. But at least now there’s a decent reason to watch.