Assistant

Vertex Pharmaceuticals Inc. said it plans to start enrolling patients in March in a 24-week Phase III study evaluating its protease inhibitor telaprevir in treatment-naïve hepatitis C virus (HCV) patients, but news that the firm would need data from an additional 48-week trial for regulatory filing sent shares falling 10.5 percent as investors worried about a delay to market.

To date, telaprevir's appeal has been the fact that it is able, in combination with standard therapy of ribavirin and interferon, to produce a sustained viral response in genotype 1 HCV patients at 24 weeks, half the time required for standard of therapy alone. Preliminary data from a European Phase II study, reported in November, showed that 65 percent of 81 patients on the so-called "12-plus-12" regimen (12 weeks of telaprevir given orally three times daily followed by 12 weeks of standard of care) had undetectable HCV at the end of that period, and they remained clear when tested 12 weeks later. (See BioWorld Today, Nov. 6, 2007.)

While the Cambridge, Mass.-based firm remains confident that telaprevir, pending positive Phase III results, will get labeling as a 24-week treatment, the FDA has asked for the additional 48-week trial. Vertex Chief Medical Officer John Alam explained during a conference call that the requirement stems from an October 2006 advisory committee meeting, at which regulators determined that the primary track to market is a study testing the drug in combination with 48 weeks of ribavirin and interferon treatment.

"Our primary hurdle working with the FDA has been the 48-week" treatment duration, Alam said. He later added that the second trial is "just to generate data showing that [telaprevir treatment at 48 weeks] is no different than [at] 24 weeks."

He assured investors that the first 24-week study would be the "primary Phase III trial." It is designed to enroll about 1,050 HCV patients, who will be randomized to one of three treatment arms. One arm will receive telaprevir dosed at 750 mg three times daily in combination with standard of care, followed by 12 weeks on standard of care alone. A second telaprevir arm will receive the drug in combination with standard of care for eight weeks, followed by 16 weeks of standard of care alone. The third arm will serve as the control, and treat patients with standard of care only for 48 weeks.

The primary endpoint will be sustained viral response (SVR) at 24 weeks.

Alam said the goal of the 48-week study is to "confirm Phase II results" and provide supportive data to the 24-week trial.

Vertex expects to have data from both trials in hand around the middle of 2010 - at this time, no interim analyses are planned - and anticipates filing a new drug application "by the end of 2010, at the latest," said Kurt Graves, chief commercialization officer.

That means the earliest the drug could hit the market would be mid-2011, and that time frame clearly has some investors worried. Add to that the fact that Rockville, Md.-based Human Genome Sciences Inc., while announcing plans to reduce the dosage in its ongoing Phase III trial of its interferon alpha product, Albuferon, reaffirmed plans to file marketing applications in HCV by fall 2009, and investors sent Vertex's stock (NASDAQ:VRTX) dropping $2.35 Wednesday to close at $20.02. (See story in this issue.)

The company's shares have been sliding steadily over the last six months, due in part to competitive concerns related to other players in the crowded HCV market, namely Kenilworth, N.J.-based Schering-Plough Corp., which in October reported positive - some said better - Phase II data showing that its oral protease inhibitor, boceprevir, achieved a high rate of early virologic response in combination with standard of care, with up to 79 percent of patients having undetectable virus at week 12. (See BioWorld Today, Oct. 19, 2007.)

Other firms with HCV protease inhibitors in development include Brisbane, Calif.-based InterMune, which is in Phase Ib testing with ITMN-191 in partnership with F. Hoffmann-La Roche Ltd., of Basel, Switzerland, and Watertown, Mass.-based Enanta Pharmaceuticals Inc., which, in collaboration with Abbott, of Abbott Park, Ill., is working on early stage HCV protease inhibitors with the potential for once-daily dosing.

Vertex's telaprevir is being developed in collaboration with Johnson & Johnson firm Tibotec Pharmaceuticals Ltd., which is handling development and commercialization in Europe, South America, Australia, the Middle East and other countries outside the U.S. Tibotec started a Phase II study late last year to test twice-daily and thrice-daily dosing of telaprevir plus standard of care in genotype 1 HCV patients and also has an ongoing Phase II trial evaluating the drug in patients infected with genotype 2/3 HCV. Results from those studies are expected in the second half of this year.

In addition to the upcoming Phase III program, Vertex is in the middle of a Phase IIb study testing telaprevir plus standard of care in previously treated genotype 1 HCV patients who failed to achieve SVR on pegylated interferon-based treatment. The firm also has plans to start clinical testing of telaprevir in combination with other investigational HCV therapies this year.

Vertex executives declined to comment on the cost of the Phase III telaprevir program, but Chief Financial Officer Ian Smith said the firm, which had cash, equivalents and securities totaling $514.5 million as of Sept. 30, ended 2007 in a "strong position." He added, however, that additional financing likely will be needed. "I'm not going to be specific on the timing," he told investors, "but we do need to bring capital into the company."

The firm, which expects to report its fourth-quarter and full-year earnings next month, recorded a net loss of $93.2 million, or 72 cents per share, for the third quarter. Its research and development costs for the three-month period totaled $128.9 million.