BioWorld Insight article "Telaprevir Looks Ever-Better, But Don't Discount Boceprevir"

BioWorld Insight - Aug. 16, 2010

HCV Wars

When Vertex Pharmaceuticals Inc. reported its first Phase III data for hepatitis C virus (HCV) protease inhibitor telaprevir in May, analysts predicted the 75 percent cure rate would be pretty hard to beat.

They were right. Earlier this month, Merck & Co. Inc.'s competing HCV protease inhibitor boceprevir reported a 66 percent cure rate in two Phase III trials. Piper Jaffray analyst Edward Tenthoff wrote that the lower cure rate was the "nail in the coffin" for boceprevir.

Other analysts echoed that sentiment last week, when Vertex reported a 72 percent cure rate in its second Phase III telaprevir trial. Wedbush PacGrow analyst Katherine Xu predicted that boceprevir will be able to capture just 40 percent of the market for treatment-naive HCV patients and 10 percent of the market for treatment-experienced patients. (See BioWorld Today, Aug. 11 , 2010.)

But don't count boceprevir out of the race just yet.

"Certainly not all of the data from either company has been reported yet," said Merck director of communications Bob Consalvo, referencing the fact that details will be presented this fall at the 2010 annual meeting of the American Association for the Study of Liver Diseases (AASLD).

Additionally, Merck reported boceprevir data from one treatment-naive trial and one treatment-experienced trial, while Vertex thus far has reported telaprevir data from two treatment-naive trials. The data from Vertex's pivotal Phase III treatment-experienced trial are expected next month.

Xu predicted that, on the whole, Vertex's treatment-experienced REALIZE trial might not have an overall cure rate as high as Merck's treatment-experienced RESPOND-2 trial. She noted that Vertex's trial includes null-responders who are hard to treat patients who did not respond to the standard of care while Merck's trial does not. "We believe stratification according to prior response is needed for a fair comparison" between the trials, she wrote in a research note.

Consalvo noted that claiming one population of HCV patients is harder to treat than another is "dicey," and can be impacted by when initial response is tested and what assays are used. He predicted that determining the best ways to measure a patient's responsiveness will become a key topic for clinicians to discuss moving forward.

Another topic expected to command plenty of focus at AASLD is response-guided therapy. Both Vertex and Merck have been using early viral load measurements to determine whether patients would need a full 48-week course of treatment, or if they could stop early and still get a cure. Given the nasty side effects associated with HCV drugs, a shorter duration of treatment would be a boon for doctors and patients.

Vertex tested response-guided therapy in its two treatment-naive trials, but not in its treatment-experienced REALIZE trial. Consalvo noted that Merck's treatment-experienced RESPOND-2 trial did test response-guided therapy and found that early responders who stopped treatment after 36 weeks rather than continuing for 48 weeks still achieved a 59 percent cure rate. Compared to a 21 percent cure rate for the group who did not get boceprevir, that's "a really good result," Consalvo said.

He added that the "opportunity for patients to have a high [cure rate] and stop treatment early . . . is significant."

But even if Vertex's cure rates in REALIZE trounce Merck's in RESPOND-2, there's another reason that both drugs may find a place in the market: resistance. Many of the patients in both companies' treatment-experienced trials are "relapsers" who had a strong initial response to the standard of care but eventually developed resistance. It's an issue that plagues all anti-infectives and requires a steady stream of new drugs.

In fact, Consalvo cited resistance as the reason Merck decided to exclude null-responders from its RESPOND-2 trial. Although both boceprevir and telaprevir are given on top of the standard of care, patients who don't respond to that standard would essentially be receiving just the protease inhibitor, which Merck felt could contribute to resistance.

That's something that will have to be hashed out in the real world as well, Consalvo said. Is treating null-responders, who will likely have a low chance of responding to the protease inhibitors as well, worth the risk of resistance? Such questions will need to be answered on a case-by-case basis, Consalvo said.