Napoleone's innovative work on VEGFFintan Walton:
Hello and welcome to PharmaTelevision News Review here at the Economist's Innovation Awards 2012, at BAFTA, in London. On this show I have Napoleone Ferrara, who is from Genentech, who has just won the Bioscience Award here at the Economist Innovation Awards.
Napoleone Ferrara:
Thank you.
Fintan Walton:
Again congratulations on that award, that award it goes back to the science that you did at Genentech on the vascular endothelial growth factor, VEGF, tell us just a little bit about how you just got into this field of VEGF?
Napoleone Ferrara:
Well, I think the idea that angiogenesis is important in a number of physiological and pathological events is very old, it's not a new idea, that's backed to the early decades of this century. People do lots of hypothesis, for example not only embryonic development or a number of physiological processes that require the blood vessels, because the blood vessels bring nourishment, which is essential for growth. Now what was also medically important is a number of disease, like for example tumor, or some eye disease which will result in blindness, are characterized by this excessive growth of blood vessels, yes obvious of course it lead to the idea that there are some factors, some mediators of blood vessel growth which is also called angiogenesis and as there has been search for decades for this angiogenic factor there, really that's where my work ended up playing a role. I was a Postdoctoral Fellow with the UCSF at the University of California in San Francisco, and actually I was studying a very different field, I was studying the pituitary gland and I discovered some certain cells in the pituitary producing some factor which induce the blood vessel growth, at that time I was very fascinated by this phenomenon, I had no idea that whether or not could be important or not and I ended up following up over the years, I studied this, trying to isolate this molecule which turned out to be a protein and actually completed this work when I joined Genentech in 1988.
Fintan Walton:
Right, now of course working in a biotech company and at that stage Genentech was you know one of the leading biotech, it still is, but it was one of the growing, rapidly growing biotechnology companies, and of course to do science you have to have time to do it and so forth, so was this part of a main stream program or was just part of the time that you could spend discovering things for yourself?
Napoleone Ferrara:
Well in fact you know this was really a great aspect of Genentech which I would end up and I appreciate very quick, I was hired because I have a background in the Reproductive Endocrinology, they hired me to work in a completely different field there on a reproductive drug called Relaxin which actually didn't work, it didn't have any effect, but at the same time in the company there this policy allowing people some free time to pursue their own research interest, that's really this work on angiogenesis on VEGF ended up , I spent my time as, sometime I think I spent probably most of my time trying to isolate this factor which turned out to be VEGF. So it was not, certainly not the main stream work, it was part of this discretionary work.
Fintan Walton:
Okay, and of course then at that time it was important to clone the gene, and that's what you did?
Napoleone Ferrara:
Well yes in those days it was important, the first you know to isolate the protein and then sequence it, this was really in those days really the path to the discovery, you are starting off from the protein then you isolate it, that was a very tedious work which take, could take years, and then once you've the sequence you are designing a probe based on that sequence and you clone it, it is was really a open up or a new area of discovery, because of course here we can make recombinant protein, you can make antibody, you could study the gene, et cetera, et cetera. So this was really, really critical step.
Fintan Walton:
Right, so that was the breakthrough to be able to get the gene cloned and then start to be able to produce sufficient quantities of it to start analyzing it?
Potence of VEGF within angiogenesisFintan Walton:
So that opened up the whole area of how VEGF works, what's its potence within angiogenesis?
Napoleone Ferrara:
Exactly, at that time when I started this work, of course there are lots of hopes that this could be, turn out to be an important factor, but in truth we knew nothing we knew absolutely nothing, as at it took years before we established the importance of VEGF, a critical tool was to develop into a antibodies to VEGF which allow us to establish its function by blocking it's effects and one of the things that we discovered actually was that blocking of VEGF had a very profound effect on tumor growth and this was really lead to the clinical development of a drug called Bevacizumab or Avastin and which then lead to develop other drugs made by other companies.
Fintan Walton:
Exactly, so Avastin now is one of the big blockbuster drugs?
Impact and efficacy of VEGF inhibitor in restoration of visual-eye-QFintan Walton:
And did you realize that when you were doing your early stage research that you would end up with an impact like that?
Napoleone Ferrara:
Well at that time it was very difficult to tell, because there was a lead, it was very widely known that actually that most of the drugs and most of the preclinical work, even successful preclinical work most of the time it failed which was late into a clinical, in the clinical success actually, it's known that about 95% of Phase III clinical trial in oncology fail, even though you can have some good preclinical data, so in a way it was an incredible surprise. Now what was even more surprising was the impact of this VEGF inhibitor in eye disease which lead to blindness like macular degeneration, in this case I think it has been, there was a dramatic efficacy which is been possible using this VEGF inhibitor to restore the visual Eye Q to a very significant proportion of patients.
Fintan Walton:
Napoleone, I want to congratulate you again. And thank you very much for coming on the show.
Napoleone Ferrara:
Thank you very much Fintan.