"HCV is an area in which Roche is highly interested," stated David Smith, a principal research scientist at Roche (www.roche.com). Currently, Roche has several products for HBV and HCV on the market: Pegasys (peginterferon alfa 2a, 40KD) for hepatitis B and C; Pegasys plus Copegus (peginterferon alfa-2a,40KD, plus ribavirin) for hepatitis C, which includes patients with normal ALT or co-infected with HIV; and Roferon (A-interferon alfa 2a) for hepatitis B and C.
"What is available now is effective in 80 percent of people who have genotypes 2 and 3 of the disease," said Smith. However, when you are looking at those who have genotype 1maybe 50 percent of all 170 million or so people infectedyou are only looking at about 40 percent effectiveness. We need to do better than that."
To that end, Roche is currently working on a polymerase inhibitor R1479 and its prodrug R1626. "Nucleosides are being shown to be a highly effective form of treatment," Smith said. "Using computational models, we targeted specific areas of the virus. We noticed that elongation occurs at the three-prime position, so we decided that the four-prime position was the area we wanted to target."
Roche took the prodrug R1626 into a Phase Ib, a two-week multiple ascending-dose study in HCV genotyope 1 patients. "We saw an increase in the amount of compound circulating and as a result, a clinically significant viral load reduction. We are encouraged by the results," commented George Hill, senior director of clinical research.
In this Phase I study, patients were randomized to receive either oral treatment with R1626 or placebo for 14 days with 14 days of follow-up. The preliminary data obtained from the 500-mg and 1,500-mg twice-daily doses were presented at the ൱st Annual Meeting of the European Association for the Study of the Liver (EASL)," held in April. The study found that at the 1,500-mg twice-daily dose, R1626 was associated with clinically significant reductions from baseline in serum HCV RNA (a measure of how much virus is in the blood) of 1.2 log10 (group mean). In addition, at both 500-mg and 1,500-mg twice-daily doses, R1626 was well-tolerated in patients with no serious adverse events and no premature withdrawals.
The study is ongoing and higher doses of R1626 are being evaluated. Future Phase II studies with R1626 in combination with Pegasys, with or without Copegus, are also planned. "We certainly need a better treatment option for our patients. The new oral polymerase inhibitor R1626 shows promising results and provides the opportunity of new combination therapy with Pegasys," Hill said.
"Eventually, we hope to be able to achieve a shorter treatment duration and better safety and efficacy."