Vertex Expects Shorter Duration Of Therapy Will Give Telaprevir Long Reign Atop Market

With high SVR rate and quad therapy showing potential for 12-week treatment period, telaprevir may enjoy short- and long-term market success.

Telaprevir has not yet reached the market as a potential game changer in hepatitis C therapy but Vertex Pharmaceuticals already is working to counter conventional wisdom that its oral protease inhibitor will dominate the HCV market quickly but be overtaken in just a few years as competitors' drugs arrive on the scene.

Addressing the J.P. Morgan Healthcare Conference Jan. 10 in San Francisco, Vertex executives outlined the company's ambitious series of clinical programs aimed at demonstrating telaprevir's efficacy, its potential to reduce the duration of therapy for hepatitis C, and its possible use in other therapeutic settings, such as patients co-infected with HCV and HIV.

At present, Cambridge, Mass.-based Vertex is in a race with Merck & Co. to get the first oral protease inhibitor for HCV approved in the U.S. and Europe - both companies completed rolling NDAs this past November and are hoping for U.S. approvals in May (Also see "Merck May Be Positioned For First Approval Of A Protease Inhibitor In HCV" - Pink Sheet, 6 Jan, 2011.). Each would be added to the current standard of care: ribavirin, a once-daily pill, and pegylated interferon, a weekly injection. The standard of care currently is prescribed for an arduous 48-week course of therapy, exacerbated by interferon's flu-like side effects.

In combination with standard of care, telaprevir already has shown the ability to achieve sustained viral response (SVR) in about 75% of patients over a 24-week response-guided therapy (RGT) treatment period. By contrast, Merck's boceprevir, in RGT, has reduced length of therapy to 36 weeks and in some cases 28 weeks.

Because of telaprevir's combination of strong efficacy - the current standard of care produces an SVR rate below 50% - and ability to reduce treatment duration, Vertex believes the drug will set a very high standard that will be difficult for competitors' drugs and drug combinations to match, let alone outperform.

High Regulatory Hurdles For Competitors Expected

If telaprevir is approved, potential competitors likely will have to prove non-inferiority, at the least, to gain approval, said Vertex Chief Medical Officer Peter Mueller, addressing a breakout session following Vertex' formal presentation at JPM. A non-inferiority trial based on a margin of 10% - that the drug produces a treatment effect within at least 90% of telaprevir's effect - would require about 1,500 patients, while a superiority trial might require 2,000 to 2,500 patients, he explained. Either would be a very expensive and time-consuming proposition.

"I have heard that telaprevir is going to go out great because there [are] all these patients waiting, but everybody else has got these better drugs," said CEO Matthew Emmens. "Somebody is going to have to show me an all-oral combination of two drugs that works, because I think it's going to be a very, very high bar."

Potentially setting the bar even higher, he added, is an ongoing Phase II trial in which telaprevir is being tested along with Vertex's experimental polymerase inhibitor, VX-222, along with standard of care in 12-week regimens. One arm is investigating 1,125 mg of telaprevir twice-daily along with 100 mg of '222 twice-daily, while another combines the same dosage of telaprevir with 400 mg of '222 twice-daily. Vertex expects data from both arms this quarter.

Vertex also will begin enrolling patients in an interferon-sparing study, testing telaprevir and '222 with just ribavirin this quarter. In December, the company discontinued a pair of trials testing a regimen of just telaprevir and '222 due to a pre-defined stopping rule related to viral breakthrough, a rebound of viral RNA in the blood during treatment after the count had dropped to undetectable levels (Also see "Drop Two, Add One: Vertex Adjusts Adaptive Trial Seeking An All-Oral HCV Regimen" - Pink Sheet, 23 Dec, 2010.).

In addition to those efforts, Vertex also is running a Phase IIIb trial evaluating the efficacy of a 1,125 mg twice-daily dose of telaprevir against a thrice-daily dose of 750 mg, the dosing regimen included in the FDA and European Medicines Agency filings. Vertex expects data from the OPTIMIZE trial by 2012, with plans to submit a supplemental NDA for twice-daily dosing by the end of 2012.

In tandem with European co-development and commercialization partner Johnson & Johnson, Vertex also is planning a Phase III trial testing telaprevir in patients infected with both HCV and HIV, as well as a Phase II study of telaprevir-based regimens in patients with recurrent HCV following liver transplant.

With more than $1 billion cash and equivalents in hand at the end of 2010, Vertex says it has more than enough money to bring telaprevir to market and complete its registrational program for Phase III cystic fibrosis candidate VX-770, an oral, novel CF transmembrane conductance regulator protein potentiator.

Vertex Confident About Reimbursement Success

Despite the earning potential of its two lead programs, Vertex is often active in the capital markets because of its deep, active pipeline and lack of income-generating products - the biotech reported a net loss of about $750 million in 2010.

In a Jan. 10 note, J.P. Morgan analyst Geoffrey Meacham said significant revenues should be right around the corner for Vertex, but warned that reimbursement hurdles could slow telaprevir's trajectory toward blockbuster status.

"While we have no doubt that telaprevir will be a blockbuster in the future, we caution that biotech drug launches can disappoint (reimbursement pathway can take six-plus months to establish in some cases)," he wrote. "Additionally, we do not believe a formidable market competitor in Merck can be completely disregarded, independent of clinical data."

Emmens, however, predicted that telaprevir would slide through the reimbursement process in managed care easily, because Vertex will be offering a therapeutic alternative with a superior cure rate and the ability to stave off greater long-term costs, both in terms of reduced duration of therapy and fewer treatment-failure patients needing additional care.

"It is pretty much the same with every drug that we are working on," he said. "The economics work because the drugs are working on things that have consequences that are much worse later."

-Joseph Haas ([email protected])