West Coast Editor

Wall Street nicked shares of Vertex Pharmaceuticals Inc. on word of results from two Phase IIb trials with its protease inhibitor telaprevir, as investors apparently were turned off by somewhat lower than expected sustained viral response (SVR), though the drug beat standard of care.

Vertex's stock (NASDAQ:VRTX) closed Friday at $28.90, down $2.74, after trading as low as $26.65.

Before presenting the interim analysis of data at the American Association of the Study of Liver Diseases meeting in Boston, Vertex said 61 percent of 79 patients in the U.S. trial called PROVE 1 gained undetectable viral levels at 24 weeks after stopping therapy, which consists of telaprevir plus standard of care: pegylated interferon plus ribavirin.

In the European study, PROVE 2, 65 percent of 81 patients on the "12 plus 12" regimen - 12 weeks of the telaprevir pill thrice daily, followed by 12 weeks of standard of care - got rid of their HCV and stayed clear when tested 12 weeks later.

"We're only at the midstage, and we'll need to run large confirmatory trials, but this is really the strong signal that we may be able to improve care," treating patients in a cycle that is half the 48-week term used in ordinary standard-of-care therapy, said Michael Partridge, director of corporate communications for Cambridge, Mass.-based Vertex.

Side effects included rash, anemia and gastrointestinal disturbances, with severe adverse events proving almost the same in PROVE 1's telaprevir and control arms, 27 percent and 24 percent, respectively. Those numbers could come even closer together in PROVE 2, after patients on the pegylated interferon/ribavirin regimen are treated for the planned 48 weeks.

In PROVE 1, the overall discontinuation rate through 12 weeks was 18 percent across all telaprevir treatment arms and 3 percent in the control arm. PROVE 2's numbers were 14 percent and 6 percent. Partridge said the Phase IIb results will help manage patients' adverse events better.

"We're in discussions with the FDA around these data and how best to study telaprevir going forward," Partridge said. Analysts at Needham & Co. wrote in a research report Friday that telaprevir is "likely to be a drug," but were "concerned by Phase III timing and trial design," and said guidance by Vertex's management is aggressive.

"We expect a large Phase III trial to begin in early 2008, with a 72-week standard-of-care arm to generate comparable 24-week SVR data," wrote analyst Alan Carr and Mark Monane, noting that the start of the Phase III trial could be delayed further into 2008 if the FDA wants to review full 24-week SVR data before talking about Phase III protocol.

Meanwhile, competitor Roche Holdings AG had HCV news from the liver meeting Friday as well. Basel, Switzerland-based Roche said results from its 950-patient REPEAT (Retreatment with Pegasys in Patients Not Responding to Peg-Intron Therapy) study showed that therapy with the firm's pegylated interferon Pegasys once weekly plus daily ribavirin for 72 weeks is a promising treatment option for patients whose infection did not respond to previous treatment with another pegylated interferon, Peg-Intron, from Kenilworth, N.J.-based Schering-Plough Corp., plus ribavirin. Data showed response at 12 weeks could predict the eventual outcome, too, with the majority of patients with undetectable virus at that stage going on to achieve SVR after 72 weeks of treatment, while few patients with detectable virus at 12 weeks achieved SVR.

The race for a better HCV therapy continues, as companies strive to come up with something that works better than the standard of care's 40 percent to 50 percent cure rate.

Vertex took a hit last month when Schering-Plough reported better than expected Phase II results with its oral protease inhibitor for HCV. Initial data from the ongoing study in treatment-naïve patients showed that Schering's boceprevir combined with pegylated interferon and ribavirin gained a high rate of early virologic response, with up to 79 percent of patients showing undetectable virus at week 12 compared to 34 percent of patients given only the standard of care. (See BioWorld Today, Oct. 19, 2007.)

Others making earlier-stage news in recent weeks include Enanta Pharmaceuticals Inc., of Watertown, Mass., which said HCV protease inhibitors demonstrated antiviral activity in the cell-based replicon assay and had favorable preclinical pharmacokinetic properties with the potential for once-daily dosing in humans.

Enanta partnered with Abbott Park, Ill.-based Abbott in 2006 to develop and sell HCV protease inhibitors, with the HCV NS 3/4A serine protease at the center of the deal.

Los Angeles-based Canopus BioPharma Inc. disclosed plans to move its HCV compound, CB5300, into trials after screening identified a family of molecules capable of inhibiting flaviviruses. And Inovio Biomedical Corp., of San Diego, said partner Tripep AB, of Huddinge, Sweden, has begun enrolling patients for its Phase I/II study of a novel DNA vaccine designed to treat chronically infected HCV patients.

That trial will test Tripep's DNA vaccine, ChronVac-C, administered using Inovio's MedPulser DNA delivery system, in 12 infected subjects.