Mae FV-100 yn gyffur gwrth-feirysol, sy’n anelu at leddfu poen miliynau o ddioddefwyr yr eryr (shingles) ledled y byd.
Mae'r cynnwys isod ar gael yn Saesneg yn unig.
Over two million people around the world are affected by shingles on an annual basis. But now a new, powerful, antiviral agent has beendeveloped, in part, by Cardiff University researchers.
A new discovery
In the mid-1990s, researchers led by Professor Chris McGuigan at Cardiff University discovered an entirely new family of antivirals - the bicyclic nucleoside analogues (BCNAs). Working in conjunction with Professor Ian Balzarini from the Rega Institute of Katholieke Universiteit Leuven, Belgium,the team conducted virology tests on these new antivirals. They found that the alkyl BCNAs to be potent and selective agents active against the Varicella Zoster Virus (VZV) - the cause of human chickenpox and shingles.
The molecules synthesised in Professor McGuigan's BCNA research programme represented completely new chemical entities with an initial 'hit molecule' being around 250-times more powerful in vitro than the first-line drugs against VZV, acyclovir and its valyl ester (Valtrex).
Subsequent work to generate second generation aryl BCNAs revealed that the lead candidate, Cf1743, was the most potent inhibitor of VZV ever discovered - roughly 10,000-times more active than acyclovir in vitro.
Cardiff University took the lead to exploit the potent anti-VZV BCNA agents and licensed the patents to Fermavir Pharmaceuticals who worked with the research team to develop FV-100 as a novel orally bioavailable pro-drug. This research and development was highly collaborative with Professor McGuigan carrying out drug design and synthesis, Professor Balzarini performing the antiviral assay and various contract research organisations undertaking pre-clinical regulatory work.
Pre-clinical research and development on FV-100 was completed in 2007 and the agent entered phase one clinical trials in 2008, with phase 2 trials successfully concluded in 2010.
The development of anti-VZV BCNAs has been driven by major financial investment from the commercial pharmaceutical sector, realised through three acquisition deals related to FV-100 assets and highly skilled jobs in Cardiff and internationally.
A combination of promising outcomes in human clinical trials, and the effective collaborative research partnership between the research team and Fermavir, led to the US pharmaceutical company Inhibitex Inc. to acquire Fermavir in 2007. As FV-100 was Fermavir's only main drug asset, the purchase of the company placed a direct market valuation on the antiviral agent - more than $19M.
The success of further clinical trials contributed to the acquisition of Inhibitex by Bristol-Myers Squibb (BMS) followed by Synergy Pharmaceuticals (New York), a NASDAQ listed company currently valued at $400M, and later Contravir Pharmaceuticals.
FV100 entered phase 3 registration trials in 2015, bringing hope to the millions of shingle sufferers around the world.
Detholiad o gyhoeddiadau
- McGuigan, C. and Balzarini, J. 2009. FV100 as a new approach for the possible treatment of varicella-zoster virus infection. Journal of Antimicrobial Chemotherapy 64 (4), pp.671-673. (10.1093/jac/dkp294)
- McGuigan, C. et al. 2007. Preclinical development of bicyclic nucleoside analogues as potent and selective inhibitors of varicella zoster virus. Journal of Antimicrobial Chemotherapy 60 (6), pp.1316-1330. (10.1093/jac/dkm376)
- Balzarini, J. and McGuigan, C. 2002. Bicyclic pyrimidine nucleoside analogues (BCNAs) as highly selective and potent inhibitors of varicella-zoster virus replication. Journal of Antimicrobial Chemotherapy 50 (1), pp.5-9. (10.1093/jac/dkf037)
- McGuigan, C. et al. 2000. Highly potent and selective inhibition of varicella-zoster virus by bicyclic furopyrimidine nucleosides bearing an aryl side chain. Journal of Medicinal Chemistry 43 (26), pp.4993-4997. (10.1021/jm000210m)
- McGuigan, C. et al. 1999. Potent and selective inhibition of varicella-zoster virus (VZV) by nucleoside analogues with an unusual bicyclic base. Journal of Medicinal Chemistry 42 (22), pp.4479-4484. (10.1021/jm990346o)
This research was made possible through our close partnership with and support from: