Hep C Drugs Slug It Out

When a drug seems destined for approval, it's easy to get so excited about its prospects that you discount its competition. Last month, Vertex Pharmaceuticals (Nasdaq: VRTX) produced very strong study data on its lead antiviral hepatitis C drug, telaprevir, at the European Association for the Study of the Liver (EASL) annual meeting. But the resulting excitement may have blinded analysts and investors to an equally promising rival.

Digging through the data
The contender in question is boceprevir, a hepatitis C treatment from Schering-Plough (NYSE: SGP). Though Vertex's impressive results led EASL attendees to crown telaprevir the superior protease inhibitor, the data is not as clear-cut as it seems.

Patients treated with telaprevir in Vertex's PROVE-1 and PROVE-2 phase 2 studies experienced respective cure rates (what is known as a sustained virologic response, or SVR) of 61% and 68%. If its current results hold up, only 55% and 57% of patients in the two groups of Schering's phase 2 SPRINT-1 study have thus far achieved undetectable levels of hepatitis C virus 12 weeks after their boceprevir treatments ended.

So telaprevir's efficacy tops boceprevir's, right? Not yet. We'll first need to know how SPRINT-1's patients fared compared with the study's control group.

The population problem
Variables such as weight, initial viral count, and a patient's race can alter the effectiveness of hepatitis C treatments. Multiple studies have shown that for whatever genetic or virologic reason, African-American patients respond significantly worse to hepatitis C treatment than some other patient groups.

In the SPRINT-1 study, 16% of patients were African-American, compared to only 10% in PROVE-1, and less than 6% in PROVE-2. Unfortunately, the SPRINT-1 control group SVR data isn't out yet, so these demographics are the only way to judge which drug faced a potentially less-responsive patient population.

Interim study efficacy results do suggest that the SPRINT-1 study faced a rougher battle, even beyond patient characteristics. Only 34% of the SPRINT-1 control group patients were measured as having undetectable levels of hepatitis C in their blood after 12 weeks of treatment, compared to 39% of control patients in the PROVE-1 study, even though both control groups received similar standards of care (Pegasys and PEG-Intron).

This is important; this early viral response data is linked to the number of patients who will ultimately be declared cured. The data suggests that SPRINT-1's control group will yield lower cure rates than PROVE-1 and PROVE-2's did.

Interestingly, the studies' differing demographics could not only explain the apparent efficacy gap between boceprevir and telaprevir, but also the PROVE-2 study's higher cure rate than PROVE-1's. Both PROVE-1 and PROVE-2 produced cure rates 20 percentage points greater than those of their respective control groups. Once the SPRINT-1 control group's longer-term cure rate data is released, we'll be much better able to compare its effectiveness with the PROVE studies.

The comparisons don't end with efficacy
On the safety side of the equation, both drugs have prompted similar numbers of patients to drop out  because of adverse events. SPRINT-1 dropout rates ranged between 11% and 15% in the study's various groups of boceprevir-treated patients, compared to 8% in the control group. PROVE-1 and PROVE-2 dropout rates were a combined 17% in telaprevir-treated patients, and 10% in the control groups.

Right now, telaprevir is ahead in the race to be the first antiviral hepatitis C agent on the market. Its efficacy and safety data -- which, as ViroPharma (Nasdaq: VPHM) has shown, are mighty important -- are also much better-known than boceprevir's because it has been tested in more patients and in a wider variety of studies. All things considered, telaprevir is a safer bet than boceprevir to reach the market at this point.

However, claiming that telaprevir is better than boceprevir, or superior to some of the polymerase and other protease inhibitors from InterMune (Nasdaq: ITMN), Johnson & Johnson (NYSE: JNJ) and Medivir, or Pharmasset (Nasdaq: VRUS), is a dangerous gamble -- at least until we learn how boceprevir's results in SPRINT-1 differed from those of its control group.