Telaprevir Prospects Improve With Positive Findings In Twice-daily Dosing

Vertex reports trial data on hepatitis C candidate show twice-daily dosing efficacy, increased sustained virologic response.

With industry analysts questioning how much advantage protease inhibitor telaprevir will enjoy in the hepatitis C arena - even if it is first to market - Vertex Pharmaceuticals has begun shifting expectations with data showing a potential for twice-daily and superior sustained virologic response.

Cambridge, Mass.-based Vertex and its ex-U.S. commercialization partner Tibotec are conducting several Phase III trials of telaprevir, though the Phase IIb trial measuring efficacy and safety of twice-daily and three-times-daily dosing may have the most impact on market potential.

During Vertex's first-quarter earnings call April 21, Chief Medical Officer John J. Alam detailed early data from that study, using telaprevir in combination with pegylated interferon alfa-2a (Roche's Pegasys ) or peginterferon alfa-2b (Schering Plough's Pegintron ). Three tablets comprising 1,125 mg were given every 12 hours or two tablets totaling 750 mg were given every eight hours.

Early pharmacokinetic analysis supports continuation of the twice-daily dose study, Alam said.

"Specifically, preliminary pharmacokinetic analyses of pre-dose samples taken on day 8 of dosing in approximately 50 patients indicate that the trough concentration in these patients receiving a twice-daily telaprevir-based dosing schedule were approximately 2,300 ng/ml, a value that is better than we expected and similar to the trough concentration of the three-times-daily telaprevir-based dosing schedule in the study," he said.

This concentration is close to that observed in the Phase II PROVE 1 and PROVE 2 trials, he added, which dosed three times daily and demonstrated substantial increase in SVR compared with the standard of care.

Several competitors, including Schering-Plough, Medivir, Roche, InterMune and Boehringer Ingelheim, are developing protease inhibitors for HCV (¹ (Also see "Protease Inhibitors Line Up To Challenge Vertex In HCV" - Pink Sheet, 18 Mar, 2008.)). While Vertex is on pace to reach the market first, that advantage has been questioned because of the expectation that its drug would require thrice-daily dosing.

In an April 22 note, analyst Nicole Keeler of Cowen & Company wrote, "We view this initial data as highly encouraging, although we remain cautious in declaring [telaprevir] a twice/day product until we have antiviral data as well as 12-week safety data."

Meanwhile, Vertex unveiled top-line data from the PROVE 1 trial and an updated interim analysis of PROVE 2 during the European Association for the Study of the Liver conference April 23 in Milan. The studies investigate telaprevir in combination with Pegasys and ribavarin in treatment-naive patients infected with HCV genotype 1.

A sustained viral response rate of 61 percent was achieved through 24 weeks of treatment in PROVE 1 and an SVR rate of 68 percent was seen at the same interval in PROVE 2. Control arms produced rates of 41 percent and 48 percent, respectively.

Analyst Vernon T. Bernardino of Rodman & Renshaw wrote in an April 23 note that data from those trials may give telaprevir a substantial efficacy advantage over boceprevir, Schering's HCV protease inhibitor, now in Phase II. That compound showed low rapid virologic response in trial data reported last October, followed by later findings of 34 percent SVR.

"In contrast, telaprevir recently demonstrated promising RVR (70%), which bodes well for positive SVR results and suggests that boceprevir may be a less efficacious compound," Bernardino wrote.

Vertex plans to file an NDA for telaprevir in treatment-naive HCV patients in 2010.

During the earnings call, Vertex also said it would present Phase IIa trial data on VX-770, its oral cystic fibrosis potentiator, in June at the European Cystic Fibrosis Society conference in Prague. Last month, Vertex outlined clinical data indicating the compound could be the first CF therapy to address the underlying disease rather than just its symptoms (² (Also see "Vertex Advance In Cystic Fibrosis May Treat The Underlying Disease" - Pink Sheet, 27 Mar, 2008.)).

For the quarter, Vertex reported a GAAP net loss of $96.2 million, up year to year from $80.7 million. The loss increase was due partially to a reduction in collaborative revenues, although that was offset somewhat by a drop-off in R&D expenses, the company said.

Total revenues for the quarter were $41.7 million, down from $68.8 million in the same quarter a year earlier. Vertex noted it will be recognizing a $45 million milestone payment from Tibotec in the second quarter, triggered by dosing of the first patients in the Phase III ADVANCE trial of telaprevir.

-Joseph Haas ([email protected])