Vertex Pharmaceuticals

(VRTX) - Get Vertex Pharmaceuticals Incorporated Report

is pushing ahead with an aggressive drug development plan that, if successful, will drastically improve how hepatitis C is treated across the world -- and make boatloads of money for the company and investors in the process.

If Vertex stumbles, however, the blowup will be spectacular, even by biotech standards.

The drug in question is called telaprevir. Vertex is in the midst of an ambitious phase II clnical study program that will yield crucial data over the next 10 to 12 months.

Most importantly, we'll soon know whether: 1) telaprevir can shorten treatment time for most hepatitis C patients to as little as three months, compared with about a year for current treatments; and 2) whether telaprevir can boost cure rates for hepatitis C patients to 70% to 80% or higher from about 50% today.

If the telaprevir pill can achieve all that, the drug might easily generate $2 billion to $3 billion in revenue and could double or even triple the value of Vertex shares, which closed Monday at $32.52. Likewise, the downside risk is eye-popping: Wipe telaprevir off Vertex's map, and the stock could head quickly back to the teens.

While Vertex has other drugs in the oven, the company's near-term fortunes are tied tightly to telaprevir, which is why investors need to pay attention to the outcomes of these ongoing clinical trials, which the company has dubbed PROVE 1 and PROVE 2.

But first, here's why the drug has generated so much excitement already.

Telaprevir is designed to attack hepatitis C by inhibiting the protease enzyme, one of the key enzymes used by the virus to make copies of itself. This "direct antiviral" approach differs from current hepatitis C drugs, which work by boosting the body's immune system to tamp down and eliminate the virus.

A weekly injection of alpha interferon (


( SGP) PEG-Intron or



Pegasys) combined with daily oral doses of a generic drug ribavirin is the current standard of care for hepatitis C patients. A normal treatment course for Type 1 hepatitis C (the most prevalent form) takes 48 weeks to complete. But only about half of patients are cured, and the side effects can be difficult to tolerate, including flulike symptoms, anemia and depression.

Vertex believes that adding telaprevir to the current standard of care will increase cure rates and shorten the length of treatment. Early clinical data have backed that view, although final proof will only come from longer studies in more patients. That's what Vertex intends to do with its PROVE 1 and PROVE 2 studies, which are being run in the U.S. and Europe, respectively.

For now, let's focus on PROVE 1, since that's the study that will soon yield some important data. The study has enrolled 260 patients spread across four arms:

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  • Arm 1: 12 weeks of telaprevir plus 12 weeks of alpha interferon and ribavirin (which I'll now refer to by its shorthand, PEG-IFN/RBV)
  • Arm 2: 12 weeks of telaprevir plus 24 weeks of PEG-IFN/RBV
  • Arm 3: 12 weeks of telaprevir plus 48 weeks of PEG-IFN/RBV
  • Arm 4: A "control" or comparison treatment of 48 weeks of PEG-IFN/RBV (no telaprevir).

The most important data coming from this trial will be "cure" rates, defined as the number of patients in which the level of hepatitis C virus becomes undetectable, as measured by a highly sensitive blood test. In medical parlance, this is known as the rate of "sustained virologic response," or SVR, and it is typically assessed six months after the end of treatment.

In PROVE 1, all patients have completed their 12 weeks of telaprevir dosing. Arm 1 patients are off treatment altogether (having also finished their 12 weeks of PEG-IFN/RBV), while patients in Arms 2, 3 and 4 continue to get PEG-IFN/RBV.

Vertex's stated intent is to use medical meetings as the forum for the release of clinical data, as opposed to simply issuing press releases. The first likely opportunity, then, is the European Association for the Study of Liver Disease, being held April 11 to April 15 in Barcelona. At this meeting, we're likely to get an interim update on treated patients, which will include some shorter-term measure of SVR, or cure, rates.

Looking further ahead, expect additional data at the Digestive Disease Week conference May 19 to May 24 in Washington, D.C., and the American Association for the Study of Liver Disease annual meeting Nov. 2 to Nov. 6 in Boston. (Mark your calendars.)

Vertex's stock has been weak since December, when shares were trading above $44, in part because the release of the first slug of data from PROVE 1 proved a bit disappointing to some and also raised the specter of unacceptable toxicity.

After 12 weeks of treatment, Vertex reported that 88% of patients on a telaprevir-containing arm had undetectable levels of the hepatitis C virus in their system, compared with 52% of patients in the control arm. But when these results were adjusted for the 9% of patients who dropped out for adverse events, the undetectable rate in the telaprevir arm was reduced to 80%, below the 90%-plus rate that many investors were expecting at this stage of the trial.

A higher-than-anticipated dropout rate due to toxicity was also a bit unexpected, raising concerns that telaprevir, despite its high efficacy, might have safety issues. Specifically, some anecdotal reports of severe skin rash in patients taking telaprevir raised alarm bells on Wall Street, although Vertex has vehemently denied that any such problems exist.

Vertex believes that the data generated by PROVE 1, PROVE 2 and an upcoming PROVE 3 trial, if positive, will be enough to form the basis of an approval filing with the

Food and Drug Administration

in late 2008. The company does plan on running a phase III trial, starting in the second half of 2007, to add to the drug's safety database and support its FDA application.

If Vertex can hold to this aggressive time line, telaprevir could be on the market by early 2009.

Additional clinical trials of telaprevir are also under way, including studies in hepatitis C patients who have failed or responded poorly to current treatment.

Few doubt that telaprevir is a real drug or that it will increase cure rates for hepatitis C patients -- but by how much? And will the drug's benefits outweigh its risks? The answers to these questions are still unknown but will come fairly soon from data generated in the PROVE 1 and PROVE 2 studies.

Only after that data are released will investors be able to answer the risk/reward question for considering Vertex shares.

Adam Feuerstein writes regularly for In keeping with TSC's editorial policy, he doesn't own or short individual stocks, although he owns stock in He also doesn't invest in hedge funds or other private investment partnerships. Feuerstein appreciates your feedback;

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