Selected article for: "decrease increase and IFN response"

Author: Vere Hodge, R Anthony
Title: Meeting report: 30th International Conference on Antiviral Research, in Atlanta, GA, USA
  • Document date: 2018_6_28
  • ID: tudwns0r_6
    Snippet: In a Phase I clinical study, PSI-6130 was well tolerated, there being no serious adverse events up to a dose of 9000 mg. The bioavailability was modest ($ 25%) and, encouragingly, there was only 10% conversion to the inactive uridine metabolite. In collaboration with Roche, a prodrug approach was started with the aim to increase bioavailability and, if possible, decrease the conversion to the uridine metabolite. This programme led to RG7128. In a.....
    Document: In a Phase I clinical study, PSI-6130 was well tolerated, there being no serious adverse events up to a dose of 9000 mg. The bioavailability was modest ($ 25%) and, encouragingly, there was only 10% conversion to the inactive uridine metabolite. In collaboration with Roche, a prodrug approach was started with the aim to increase bioavailability and, if possible, decrease the conversion to the uridine metabolite. This programme led to RG7128. In a 14-day monotherapy Phase II study in HCV GT1 non-responder patients, there was a 2.7 log 10 reduction in HCV RNA levels. In a fourweek combination study (RG7128 (1000 or 1500 mg bid) with pegylated IFN and RBV), there was $ 90% response rate with safety comparable to the corresponding placebo control. Certainly, this was an encouraging result but the high doses and the twicedaily dosing regimen were of concern which were unlikely to be overcome by the prodrug approach. So was there another option? Why was the uridine metabolite (PSI-6206) inactive? The Pharmasset team decided to try a different approach.

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