Vertex Pharmaceuticals announces results from Phase 1b clinical trial of VX-222

In conjunction with an oral presentation at the 45th Annual Meeting of the European Association for the Study of the Liver (EASL) in Vienna, Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced results from a Phase 1b clinical trial of the investigational oral hepatitis C virus (HCV) polymerase inhibitor, VX-222. In the trial, treatment with VX-222 for three days was well-tolerated, with all adverse events being mild to moderate in severity. Dosing with VX-222 for three days resulted in a greater than 3 log₁₀ reduction in HCV RNA across all four of the VX-222 dosing groups. No serious adverse events or treatment discontinuations were reported in the Phase 1b trial. The results from this trial support the Phase 2 proof-of-concept clinical trial of VX-222 dosed in combination with Vertex's lead investigational HCV protease inhibitor telaprevir, which is expected to complete enrollment in the second quarter of 2010. Vertex retains worldwide rights to VX-222.

“With VX-222, we believe we have a unique opportunity to broaden our commitment to improving patient care in hepatitis C and to strengthen our leadership position in the development of novel specifically targeted antiviral therapies for the treatment of hepatitis C.”

"In this Phase 1b clinical trial, treatment with VX-222 for three days resulted in a reduction in viral load across all the dose groups studied," said Maribel Rodriguez-Torres, M.D., Medical Director of Fundacion de Investigacion de Diego in Puerto Rico. "This trial was designed primarily to gain important safety and viral kinetic information to enable the continued development of VX-222 as part of novel HCV combination regimens. I am pleased that additional development efforts for VX-222 are advancing, including the first trial to evaluate a two-drug regimen of VX-222 dosed in combination with the HCV protease inhibitor telaprevir."

"These early safety and efficacy results support the evaluation of VX-222 as part of novel combination regimens for the treatment of HCV, including the first Phase 2 proof-of-concept clinical trial evaluating multiple telaprevir/VX-222-based combination regimens," said Robert Kauffman, M.D., Ph.D., Senior Vice President, Clinical Development and Chief Medical Officer of Vertex Pharmaceuticals. "With VX-222, we believe we have a unique opportunity to broaden our commitment to improving patient care in hepatitis C and to strengthen our leadership position in the development of novel specifically targeted antiviral therapies for the treatment of hepatitis C."

Trial Design

The clinical results announced today are from the Phase 1b viral kinetic portion (Part A) of a two-part Phase 1b/2a clinical trial of VX-222. This double-blind, randomized placebo-controlled, dose-ranging Phase Ib clinical trial was designed to evaluate the safety, tolerability, pharmacokinetics and effect on viral kinetics of four doses of VX-222, including doses of 250 mg every 12 hours (BID), 500 mg BID, 750 mg BID, and 1,500 mg once a day (QD), or placebo. In the trial, VX-222 was administered as monotherapy for three days. Patients then had the option to receive treatment with pegylated interferon (Peg-IFN) and ribavirin (RBV) for up to 48 weeks.

Thirty-two treatment-naïve patients with chronic genotype 1 HCV infection were enrolled in the trial, including six patients in each dose group who received 250 mg of VX-222 BID, 500 mg of VX-222 BID, 750 mg of VX-222 BID, and 1,500 mg of VX-222 QD. Two patients received placebo in each of the four dosing groups, for a total of eight patients who received placebo. Part A of the trial was conducted at 10 centers in the United States, Canada and Argentina. Of the patients enrolled in the trial, 24 patients had genotype 1a HCV infection and eight patients had genotype 1b HCV infection. Six of the patients enrolled in the trial were African American, 25 were Caucasian and one was American Indian/Alaskan.

Viral Kinetic Results

Treatment with VX-222 resulted in mean reductions in plasma HCV RNA of greater than 3 log₁₀ across the four VX-222 dose groups. Additionally, an increasing dose response was observed across the four dose groups, with the results in the 500 mg, 750 mg and 1,500 mg dose groups being very similar. The mean HCV RNA decline achieved after three days of dosing with 250 mg BID, 500 mg BID, and 750 mg BID of VX-222 was 3.1 log₁₀ (range: 2.0 to 4.2), 3.4 log₁₀ (range: 3.2 to 3.6), and 3.2 log₁₀ (range: 2.3 to 3.8), respectively. The mean HCV RNA decline achieved after three days of dosing with 1,500 mg QD of VX-222 was 3.4 log₁₀ (range: 3.1 to 3.9). In the patients receiving placebo, no notable decline in HCV RNA was observed. Similar viral declines were observed for patients infected with genotype 1a and 1b.

The results of Part A of this trial are consistent with the findings from a previously conducted three-day, five-patient viral kinetic study of VX-222 dosed as 750 mg BID. Part B of the study will evaluate 12 weeks of VX-222 dosed in combination with pegylated-interferon and ribavirin in treatment-naïve HCV patients. Part B of this trial is expected to begin enrolling patients in the second quarter.

Safety and Tolerability Results

Safety and tolerability information collected for Part A of this trial remains blinded and thus the safety information provided today includes pooled data for patients after administration of placebo or VX-222. Placebo or VX-222 were well-tolerated across all four dose groups, no severe or serious adverse events were reported and no treatment discontinuations occurred. All adverse events reported after administration of placebo or VX-222 were mild or moderate in severity. The most frequently reported adverse events occurring in at least two patients per dose group were diarrhea, headache, nausea, asthenia and fever.

VX-222 Clinical Development Plans

Data from this Phase 1b clinical trial support the clinical evaluation of VX-222 as part of novel regimens for the treatment of HCV infection and provided information for VX-222 dose selection. In addition, Vertex recently completed a Phase 1 study of telaprevir and VX-222 designed to evaluate the safety, tolerability and drug-drug interaction of telaprevir and VX-222 in 20 healthy volunteers, which also supports the evaluation of telaprevir-VX-222-based combination regimens.

In March 2010, Vertex announced plans to initiate the first clinical trial evaluating VX-222 dosed in combination with the investigational HCV protease inhibitor telaprevir. The trial will evaluate the safety and sustained viral response rates with multiple 12-week response-guided regimens of telaprevir/VX-222-based combination therapy, including two-drug regimens of telaprevir and VX-222. Vertex expects to complete enrollment in this trial in the second quarter of 2010 and expects interim clinical data from this trial in the second half of 2010.

SOURCE Vertex Pharmaceuticals Incorporated