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SAN FRANCISCO -- Every six months, hepatitis C researchers from around the world gather to discuss new ways of combating the serious liver disease. In recent years, these biannual confabs have largely revolved the development of a new, more potent class of drug that promises to bring cures to a larger percentage of hepatitis C patients than ever before.
 
Like previous meetings, the one that kicked off over the weekend here will have scientists (and the Wall Street investors and analysts who follow their work closely) talking a lot about Vertex Pharmaceuticals'(VRTX Quote - Cramer on VRTX - Stock Picks) drug telaprevir.
 
Data being presented will show once again telaprevir's impressive ability to directly interfere with and eliminate the virus that causes hepatitis C in patients who have failed previous treatments and in those who are being treated for the first time.
 
Competitors to Vertex are here too. Schering-Plough will present data on the ability of its experimental drug boceprevir to eliminate the hepatitis C virus in previously untreated patients. Companies with drugs in less advanced clinical trials, including Pharmasset, InterMune, Boehringer Ingelheim, Johnson & Johnson, Merck and Pfizer, also will be presenting new or updated data. (from Jules: there are several drugs in earlier development: the BMS NS5A inhibitor is a new class, looks very potent, and the first patient data is presented at AASLD; Genelabs has HCV NNRTIs in early development and this company was just bought by GSK; Novartis already had purchased the rights to a Genelabs HCV NNRTI; Anadys has a HCV NNRTI; Abbott has a nuke, NNRTI, and a protease program; Pfizer is presenting data on their new HCV NNRTI at AASLD; NNRTI may be able to be combined because two different NNRTIs might bind at different sites, yet to be studied in patients; at EASL in the Spring data was reported in patients on weekly IV dosing of silibin and it was very potent, an update is presented at AASLD; Idenix has several HCV drugs in early development; Nitazoxanide (NTZ) is being studied in patients, it has enhanced synergy with interferon and has shown good SVR rates in early studies with peginterferon; other companies have additional drugs in early development that will be presented at EASL 2009 and later
 
For many biotech investors, Vertex remains a central focus of these hepatitis C meetings because the company is in the midst of conducting two large phase III studies of telaprevir, with the first results expected in the first half of 2010.
 
Vertex intends telaprevir to become the first new hepatitis C drug approved in years, and one that will dramatically increase the cure rate for the disease, and do so in half the time of currently approved drugs. If the plan succeeds, Vertex will grab a large share of a multi-billion dollar commercial market opportunity.
 
There are no sure things in drug development, which is why the value of Vertex shares swing rather wildly, especially as new data is unveiled and questions -- new and old -- are raised at these gatherings of hepatitis C researchers.
 
Is telaprevir the best of this new crop of hepatitis C drugs? Will Schering-Plough catch up? Are second-generation drugs already in development more potent and more convenient than telaprevir? And if so, does that leave Vertex vulnerable?
 
Much of the most important data at this year's annual meeting of the American Association for the Study of Liver Disease will be presented Monday and Tuesday. However, the veil on some of this data has been lifted already. Here's a recap of what's available so far:
 
Vertex:
 
Telaprevir stands apart from other experimental hepatitis C drugs, including Schering-Plough's boceprevir, because it appears capable of curing the disease in large numbers of patients who have failed previous treatments. (from Jules: so far the data in the Vertex press releas shows 40% of previous null-responders to peg/RBV achieved an SVR with telaprevir+peg?RBV, which means 60% fail and can get drug resistance. Will you then be able to use a protease inhibitor again in the future along with multiple oral new drugs in combination, where the best chance of cure will occur??? We don't know the answer to that question.)
 
A phase II study known as PROVE 3 showed that 52% of patients treated with telaprevir had undetectable levels of virus in their systems 12 weeks after treatment was stopped, according to interim data from the study being presented at the meeting. Vertex had previously announced some of these results last June.
 
Patients were enrolled in PROVE 3 if they had failed previous treatment with 48 weeks of pegylated interferon and ribavirin, the current standard hepatitis C therapy. These difficult-to-cure patients were then retreated with 12 weeks of telaprevir plus interferon and ribavirin, followed by another 12 weeks of interferon and ribavirin alone for a total of 24 weeks of therapy.
 
Breaking down the 52% overall result further, 73% of patients who had relapsed after receiving the standard treatment were able to drop their viral loads to undetectable levels, while 41% of patients who had not responded at all to previous treatment likewise achieved undetectable viral loads.
 
PROVE 3 also used as a control patients who were retreated a second time with the standard interferon and ribavirin. So far, just 30% of these patients have undetectable levels of virus after 36 of a planned 48 weeks of retreatment. Final data on these control patients is not ready, but far fewer are likely to reach undetectable viral loads in the observation period following treatment, based on historical data.
 
In a previous phase II study known as PROVE 2, which enrolled treatment-naive hepatitis C patients, telepravir helped 69% of patients reach undetectable viral loads 24 weeks after treatment. By comparison, 46% of patients treated with interferon and ribavirin alone saw the level of virus fall below undetectable levels.
 
The telaprevir regimen used in PROVE 2 was the same as that used in PROVE 3 -- 12 weeks of telaprevir plus interferon and ribavirin followed by another 12 weeks of interferon and ribavirin alone.
 
In all previous and ongoing clinical trials, patients take telaprevir every eight hours, or three times a day. For competitive reasons, Vertex would like twice-daily telaprevir. Interim data to be presented at the meeting suggests twice-daily telaprevir is possible and could be better than standard therapy. However, three-times-a day telaprevir still appears to be the most potent dosing schedule.
 
Schering's drug boceprevir is posting equivalent cure rates to that of telaprevir in treatment-naive patients, although the most effective treatment cycle is twice as long.
 
According to results from the phase II SPRINT-1 study released here, 74% of patients on a 48-week boceprevir regimen saw their viral loads fall below the level of detection 12 weeks following the cessation of treatment. (from Jules: this data is in treatment-naivs, the data in treatment-experienced will not be as good as Vertex's but again combination therapy with a least 2 oral drugs achieving a big log reduction in viral load plus peg/RBV will be the best regimen, particularly for patients who have failed previous therapy and who have reduced response to peg/RBV, which includes African-Americans in particular, genotype. Perhaps the best way to evaluate one's ability to respond to triple telaprevir therapy is to conduct a peg/RBV lead-in phase then add the oral drug. This study will be conducted so lets see the outcomes.)
 
These patients began treatment with four weeks of interferon and ribavirin (a lead-in period) followed by 36 weeks of boceprevir in combination with interferon and ribavirin.
 
For patients without the four-week lead in, 66% saw their virus fall below detectable levels.
 
Using a shorter, 28-week boceprevir regimen, 55% and 56% of patients achieved undetectable viral loads with no lead in treatment, or a lead-in treatment, respectively.
 
Schering-Plough is currently conducting two phase III studies of boceprevir in treatment-naive and treatment-resistant patients.
 
Pharmasset
 
Pharmasset's drug R7128 hasn't been as broadly tested as those from Vertex and Schering-Plough, but the data generated so far has shown the drug to be very effective at tamping down the hepatitis C virus.
 
The biggest question mark hanging over the drug to date is toxicity. At an investor event Sunday, Pharmasset officials for the first time discussed in some detail the emergence of kidney toxicity seen in a safety study in monkeys.
 
According to Pharmasset, the monkey kidney toxicity is reversible and did not cause permanent damage. More importantly, no such problem has been observed in the short human studies of R7128 conducted to date.
 
Pharmasset is conducting a longer, six-month safety test of R7128 in monkeys, but at this point the company doesn't believe that the Food and Drug Administration will stop further human studies from starting in the first quarter of next year.
 
Still, judging by the volume of questions from investors at Sunday's meeting that began with the words, "I'd like to get back to those monkey studies ..." the issue isn't one that Wall Street is ready to put entirely to rest.
 
Pharmasset is developing R7128 with partner Roche, which just last week was forced to halt development of a rival hepatitis C drug derived from its own laboratories because of unacceptable safety problems.
 
This Roche setback upped the value of R7128. If the drug's safety can be verified, Pharmasset will be a hepatitis C company to watch.