A major step forward for potential anti-Hepatitis C drug, INX-189, orginally synthesised in Cardiff
22 March 2011
Inhibitex, the US biopharmaceutical company, which is working on potential anti-viral drugs with Prof Chris McGuigan’s laboratory in the Welsh School of Pharmacy, has just announced the successful conclusion of the initial phase 1 trials of INX-189 in hepatitis C patients.
This drug, first synthesised less than three years ago in the laboratory in the Welsh School of Pharmacy, is active against Hepatitis C. This disease affects some 170 million individuals worldwide (3% of the human population) and current treatment is unsatisfactory.
In the current trial, ca 50 HCV patients received either a daily oral dose of INX-189, ranging from 3 mg to 100 mg, in some cases in combination with the current drug ribavarin, for 7 days. The Company plans to present detailed results from this trial during a future scientific meeting. Preliminary data from the trial are as follows:
- No serious adverse events.
- No drug related events that increase with dose.
- Similar PK to phase 1a.
- Dose-responsive increases in viral load reduction in the range 9-100mg per day, at both 3d and 7d.
- Reductions ≥1log in viral load at 3d with 50mg and 100mg.
- Reductions ≥1log in viral load at 7d with 25, 50 and 100mg.
- Reductions of ca 1.5log with 100mg at 3d or 50mg at 7d.
- 100mg for 7d gives ca 2.5log reduction.
- Ribavirin (100mg once a day) is synergistic with our agent at 25mg daily.
Prof. Chris McGuigan with the "2011 Cardiff Inhibitex team" in the laboratory
l-r Karoline Madela (PhD), Dr Maria Arrica (Post Doc), Sarah Jones (technician), Claire Bourdin (PhD), Emma Barrett (PhD).
link to full sized image 625.5 Kb
Professor McGuigan,. who is also a member of the Board of Directors of Inhibitex, warmly welcomed this news, saying: "The outcome of these multiple dose studies in patients on INX-189 are exciting and continue to show the effectiveness of the drug in patients with heptatitis C. We now need to continue with a full phase II clinical study. INX-189 has today taken a major step closer to becoming a much needed new drug for hepatitis C infection".
“The potent antiviral activity in monotherapy and the synergistic activity observed in combination with RBV support our belief that INX-189 has the potential to play a pivotal role in future HCV combination therapy,” commented Joseph M. Patti, Ph.D., Inhibitex’s CSO and Senior Vice-President of Research. “We believe these data, taken together with the successful completion of our 13-week GLP toxicology studies, support advancing INX-189 into Phase 2 clinical trials later this year.”
For recent scientific papers describing the development of INX-189 see
Christopher McGuigan, Karolina Madela, Mohamed Aljarah, et al.
Bioorganic & Medicinal Chemistry Letters 20 (2010) 4850–4854
and
C. McGuigan, A. Gilles, K. Madela, M. Aljarah, et al.
J. Med. Chem., 2010, 4949-4957.
A current Powerpoint presentation from Prof McGuigan describing Pro Tides is available here.
See also
Press release from Inhibitex, Inc.
Anti-Hepatitis C drug INX-189 successfully completes phase 1a trial in humans
Inhibitex, Inc. company web-site
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