Washington Editor

Preliminary results of a Phase I clinical trial showed 85 percent of patients who received high dosages of Pharmasset Inc.'s R7128 in combination with Pegasys (pegylated interferon) and Copegus (ribavirin) achieved undetectable levels of hepatitis C virus (HCV) after four weeks of treatment.

News of the results sent shares of Princeton, N.J.-based Pharmasset (NASDAQ:VRUS) up 44.7 percent Monday, or $6.25, to close at $20.24.

The combination trial evaluated R7128 in 50 patients with HCV genotype-1 who previously had not been treated for the infection. R7128 is a prodrug of PSI-6130, a cytidine nucleoside analogue polymerase inhibitor of HCV that is being developed under a 2004 partnership with Basel, Switzerland-based F. Hoffmann-La Roche Ltd., Pharmasset CEO P. Schaefer Price noted Monday during a conference call.

Under that agreement, Pharmasset has received $20 million in milestone payments and is eligible to receive up to $115 million in additional milestones plus royalties "projected to be in the high teens" if a product under the program makes it to market, Price told investors and analysts.

Patients in the multicenter, observer-blinded, randomized, placebo-controlled Phase I study received twice-daily doses of either 1500-mg or 500-mg R7128 in combination with once-weekly injections of Roche's Pegasys and Copegus or Pegasys and Copegus alone, the current standard of care, said Michelle Berrey, Pharmasset's chief medical officer.

Results demonstrated that 85 percent of patients who were administered 1500-mg R7128 achieved undetectable levels of HCV after four weeks, she said. About 30 percent of patients who received the lower dose of 500-mg R7128 had undetectable levels of the infection after the same period.

However, Berrey said, only 10 percent of patients who were administered Pegasys and Copegus alone achieved undetectable levels of HCV after four weeks of treatment.

No serious adverse events were reported during the four-week treatment period, Berrey said, noting that the most common side effects reported were headache, chills, fatigue, nausea and fever. Grade 4 neutropenia was observed in 5 percent of the patients in each active dosing cohort and in 10 percent of the placebo patients, she added.

The preliminary results of the Phase I trial, Berrey maintained, showed that nucleoside polymerase inhibitors can demonstrate rapid virologic response (RVR) percentages that are similar to protease inhibitors with an acceptable short-term clinical safety profile.

"The addition of R7128 at both dose levels to the current standard of care has demonstrated a greater percentage of RVR compared to the standard of care alone, which could translate into improved clinical outcomes with longer treatment periods," Berrey explained. "In addition, the level of antiviral activity from 500 mg to 1500 mg provides flexibility in selecting doses for future clinical studies."

Berrey said her firm plans to report the final safety and antiviral activity data from the Phase I combination study in the second quarter of 2008.

Also on the HCV treatment front Monday, San Francisco-based Idenix Pharmaceuticals Inc. reported that preclinical results of its second-generation polymerase and protease inhibitor compound IDX184 exhibited 10 times greater potency than other nucleosides currently in clinical development.

In a seven-day preclinical toxicology study of IDX184, no toxicities, including gastrointestinal or hematological, were observed in monkeys at dosages greater than or equal to 600 mg/kg/day, the firm said.

In addition, Idenix reported that once-daily oral administration of 10 mg/kg of either IDX184 or the firm's other nucleotide prodrug, IDX102, produced a rapid and potent inhibition of HCV replication in HCV genotype-1 infected chimpanzees, with mean viral load reductions ranging from 1.5 log with IDX102 to 2.5-4.0 log with IDX184 after 4 days of dosing. The company said clinical data for IDX184 are expected in 2008.

Cambridge, Mass-based Vertex Pharmaceuticals Inc. also reported that it has submitted a protocol to the FDA for a Phase III clinical trial of its lead investigational HCV protease inhibitor telaprevir (VX-950).

The trial design includes a 48-week control arm and eight and 12 weeks of telaprevir treatment as part of 24-week combination treatment regimens. The firm noted that it plans to use RVR criteria to determine which patients should stop all treatment at 24 weeks.

Under an agreement with Vertex, Tibotec Inc., of Yardley, Pa., is developing and commercializing telaprevir in Europe, South America, Australia, the Middle East and other countries.

Also Monday, Brisbane, Calif.-based InterMune Inc. said it has achieved the principal goals for viral kinetic performance, safety and tolerability in its first two dosage cohorts of a Phase Ib multiple-ascending-dose (MAD) clinical trial evaluating its protease inhibitor ITMN-191 (R7227) as monotherapy in patients with chronic HCV infection.

The firm said it expects its third dosage cohort to be enrolled this month. The company added that it plans to soon advance its ITMN-191 program to study the drug in combination with Pegasys and ribavirin.

In parallel with the conduct of the ongoing MAD study, InterMune said it is preparing and will submit to European authorities the clinical trial authorization application to gain approval to begin a 14-day triple combination study of ITMN-191 with Pegasys and ribavirin in the second quarter.

InterMune said it plans to present data from all available cohorts of the current Phase Ib study at one or more scientific conferences later this year.