Following The Publication Trail of Two RSV Drugs

In a publication from 2007, investigators from Arrow Pharmaceuticals told us that A-60444 (later renamed to RSV-604) was already in Phase 2.  Since then, it has been very quiet about this compound.  Some have suggested that Novartis has stopped development [1], an impression supported by the fact that the drug is not mentioned on the Novartis Clinical Pipeline chart which lists drugs in development  [2].

We still have only scant clinical information on RSV604:  from the Phase 1 trial we only have a company poster [3],  and from the PoC trial in stem cell transplant patients there is a conference report [4].  Clearly, the data did not justify the initial enthusiasm.  And nobody really likes to tie up loose ends for an abandoned compound or work on a full-fledged publication when results were disappointing.  Nonetheless, the patients that altruistically participate in a research trial in order to advance science deserve better.

The story of GS-5806 is just the opposite.  Just a few months after study completion, the positive results are published with fanfare and great detail in the NEJM [5].  There is not only a main summary article, but also a supplemental appendix describing statistics and secondary data.  Even the full protocol is available, thanks for asking.  The Journal has an editorial ready for the occasion and a nice commentary about the ethics and history of human experimentation with infectious agents.  Everyone must have fast-tracked this publication right from the moment the blind was broken.

There is no argument here:  Patients really will benefit from a drug that works in RSV infections.  Gilead is on track with GS-5806 in this effort providing efficacy data from a nicely executed study.  Let’s give credit where it’s due:

RSV studies are notoriously difficult: there is no established precedent, there is no surrogate marker, the clinical presentation is non-specific and the virus is not causing viremia.  As a mucosal disease, there is great inter- and intraindividual variability of viral shedding over time.  Sampling respiratory secretions is a messy way of generating quantitative data.  There is also no good animal model for testing as animal strains are not infecting humans and vice versa.  Not surprisingly, the field is littered with poorly executed studies.  Therefore, my congratulations to DeVincenzo and the Gilead team for executing an innovative study successfully.

 References:

[1] H. Costello.  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3835183/
[2] http://www.novartis.com/innovation/research-development/clinical-pipeline/index.shtml
[3] J. Dent. 45^th ICAAC, Washington, DC, 2005, Poster F-483
[4] F Marty.  IXth International Symposium on Respiratory Viral Infections.  Causeway Bay, Hong Kong, Mar 3-6, 2007
[5] J. DeVincenzo.  NEJM 371: 8, 2014
[6]  www.niehs.nih.gov