Alnylam Reports “Positive” Data from RSV Experimental Infection Trial: Human Proof-of-concept for an RNAi Therapeutic?

Alnylam got observers scratching their heads today as they announced “statistically significant anti-viral activity” for ALN-RSV01, an RNAi Therapeutic against RSV infection, in an early phase II trial, but without providing further details.

In this experimental infection trial, an siRNA delivered to the nasal epithelium is tested for activity against a non-pathogenic strain of RSV. The trial has two main purposes: firstly, to provide the first demonstration of RNAi activity in man (human proof-of-concept; HPOC); and secondly, to inform the design of late-stage phase II trials in naturally infected adults slated for the first half of this year, although in that trial delivery will be to the lung by nebulizer (see 13Dec07 Blog: Breaking News: “Alnylam Reports on the Safety of Inhaled RSV-01”).

The question then arises why did they not present any hard data? It is possible that, as often the case in biotech, initial press releases and top-line data are exploited for PR purposes while the warts-and-all data turn out to be less than impressive. However, given their usually well executed PR strategy with which they have earned themselves considerable credibility, I doubt that they would start playing around with the meaning of “statistically significant”.

One possibility is that they are still crunching numbers as to viral titers by PCR and plaque assay as well as symptom scores in the different groups, to then comprehensively present the whole data set at the International Symposium on Respiratory Viral Infections meeting next month in Singapore. Some meetings also do not like it when data are presented beforehand in press releases. In any case, I hope the company makes the full data set available on their website once they are presented. I am particularly curious as to whether they allow insights into the mechanism of action of this drug.

Another maybe more intriguing possibility for the strange lack of any concrete numbers may have to do with the rather equally unusual post-hoc christening of the trial as GEMINI. Assuming that they would not want a failed trial to be well remembered by giving it a name, one that could be maliciously interpreted as to mean “ambiguous”, the naming of an early stage trial AFTER the results are announced may have a deeper meaning. If the results hold up, GEMINI could be used in the future to refer to HPOC as another momentous de-risking event in the history of RNAi Therapeutics. Equally tantalizing is the possibility that the full data presentation of GEMINI may coincide with the announcement of a co-development partner. Although the initial adult market for ALN-RSV01 may be limited, this program should attract considerable interest as it will give the partner a pioneering role in RNAi Therapeutics, potentially associated with first dips for future respiratory disease programs.

So stay tuned on GEMINI as we are likely to hear it being referred to quite more often in the future. January 23, 2008, may have been another important milestone in the development of RNAi Therapeutics. In the meantime, the prize goes to he/she who can figure out first what the acronym GEMINI stands for*.

PS: I would guess that today’s results will have triggered milestone payments from the Novartis and Roche collaborations.

[* Update May 2, 2008: It is becoming clear now that GEMINI stands for the intention of the study to both show a) proof-of-concept for RNAi efficacy in man, and b) further evaluate the safety and efficacy of ALN-RSV01 for the RSV antiviral development program.]