Vertex, Worth $7.5B, Eagerly Awaits Final Proof that Hepatitis C Drug Works

5/17/10Follow @xconomy

Vertex Pharmaceuticals has been in business for more than 20 years, and burned through more than $2.8 billion on a quest to develop drugs that shake up the medical standards of care. Now in the coming weeks and months, it will get the first definitive evidence that will say whether its lead drug candidate for hepatitis C has achieved its goal.

Investors, looking at data from preliminary and mid-stage clinical trials, have already pumped up the market value of Vertex (NASDAQ: VRTX) past $7.5 billion largely in anticipation that its drug, telaprevir, will transform the lives of patients with the chronic liver-damaging condition. But the operative word there is preliminary. Vertex, which is based in Cambridge, MA, and has significant operations in San Diego, is still waiting for its first proof from Phase III clinical trials, the final step of testing required by the FDA before a drug can go on sale in the U.S.

These pivotal trials began two years ago, and enrolled more than 2,000 patients combined in three studies. The results are completely blinded to doctors, patients, investors, and people at Vertex. To say all parties are in suspense for these results would be an understatement. They can’t wait to get their hands on the new data and start digging through it.

“This is a year of defining moments,” says Bob Kauffman, Vertex’s chief medical officer.

Vertex has generated the excitement around what could be a first-in-class protease inhibitor drug for hepatitis C. It has excited researchers because it has been able to double the cure rate while enabling patients to cut their standard course of treatment time in half. That means that many more of the 3 million Americans and 170 million people worldwide with chronic hepatitis C liver infections will be likely to seek out treatment, and be able to stand up to the side effects of standard therapy that causes flu-like symptoms. If Vertex can prove this idea once and for all in the three pivotal trials, Vertex could seek FDA approval later this year and bring telaprevir to the market in 2011. U.S. sales alone could amount to more than $2 billion after a couple years, analysts say.

Bob Kauffman

Bob Kauffman

To help our readers get ready for this data, I spoke to Kauffman for a refresher on what the three big Vertex trials were designed to ask and answer. The key point to watch for in all of these studies is what is called a “sustained viral response,” or SVR, which is recorded when researchers can’t find any sign of virus in a patient’s blood sample for a full 24 weeks after they completed their course of therapy. This is the gold standard measurement for all hepatitis C drugs, and is commonly known as a “clinical cure.”

The first study to watch for is called “Advance.” This trial, started in March 2008, enrolled 1,050 patients who had never been treated before for hepatitis C—a so-called “naïve” patient population. This study is essentially designed to confirm earlier trials called Prove 1 and Prove 2, Kauffman says. Patients either got the Vertex drug in combination with standard treatments for 24 weeks, or the standard treatments for the usual 48 weeks. The trial is designed to ask whether patients can stop treatment early with the Vertex drug, so they can avoid having to put up with the flu-like side effects of pegylated interferon alpha and ribavirin, Kauffman says. Results from that study should be available by the end of June, he says.

Not long after that data arrives, Vertex plans to hear results from two other key trials before the end of September. One of them, called “Illuminate,” is enrolling patients who have never before been treated for hepatitis C infections, just like the earlier trial. The study, which enrolled 500 patients, is also looking to see how many clinical cures it can generate, and whether there’s any benefit in subjecting patients to the standard 48-week course of therapy, or whether they do just as well in half the time, Kauffman says. “It should validate that 24 weeks is enough,” Kauffman says.

The third study, called “Realize,” is important for strategic and competitive reasons. This trial enrolled 663 patients who had previously been treated for hepatitis C, but weren’t cured. Vertex has shown some promising results in this tough-to-treat patient population in the past, which is the sort of data that can really give physicians confidence in the drug’s punch. Vertex has taken care to stratify this study into three different kinds of patients—those who benefitted for a while but relapsed, those who only partially responded to prior therapy, and those who never really benefitted at all. Patients will get telaprevir in addition to the standard treatment, or just the standard stuff, for a total of 48 weeks.

As I described back in September 2008, this study is one of the key ways that Vertex seeks to differentiate itself from a competitors that are following fast—Merck’s boceprevir.

Kauffman declined to speculate on how high the clinical cure rates will need to be for Vertex to declare victory. Last October, Vertex presented results from patients who failed prior therapy, which demonstrated telaprevir could induce cure rates between 55 percent and 90 percent. Vertex said back in April 2008, before it invested in the pivotal round of telaprevir trials, that between 61 percent and 68 percent of treatment-naïve patients were clinically cured in the smaller trials (Prove 1 and Prove 2).

After the past two years of recruiting patients, supplying the clinical sites with experimental drugs, monitoring the sites to make sure they follow the study protocol, and gathering all the data, you could say the expectations are high for this study. Wall Street, after all, is giving Vertex that $7.5 billion market valuation on anticipation of telaprevir’s sales trajectory more than any other factor. If the pivotal studies confirm the smaller trials—which is never a given in drug development—you will probably hear the victory whoops skimming all the way across the Charles River from Vertex headquarters in Cambridge.

“Phase III is the ultimate confirmation,” Kauffman says. “They are the largest and most definitive studies. It’s a very important time for us at the company now.”

By posting a comment, you agree to our terms and conditions.

  • http://statins.org Rjpatterson

    Telaprevir will be used in a “triple therapy” along with pegylated interferon and ribavirin. The problem is interferon. It is a very dangerous drug and has caused permanent nerve damage, memory problems and neuropsychiatric disorders to many people, including me. I wish the FDA would do an investigation on just how many people, were damaged by interferon. Do a google search. Read the Hepatitis C forums. You will see alot of people that was ok, before they started the treatment, and afterward was left with numerous debilitating medical problems. I wish I could sue the makers of this horrible drug interferon. It’s been two years since treatment and I live everyday in pain. Frustrated in Texas…..!

  • unsure in Michigan

    That’s why I’m looking to join a clinical trial –one that doesn’t include interferon. All I here is negative info about it.

  • Frank Mulder

    Could someone please contact me about Vertex Clinical Trials for Hep C. I cannot find one available. I live in Tampa, Florida. My phone number is 813 992-1970.

    Frank Mulder

  • RonG

    I am literally dying with hepatic encephalopathy and have developed cirrhosis with ammonia levels that will not come down. I failed the interferon combo and the side effects were horrible, but I cannot wait to try this drug out with all the side effects. Transplant does not work as you become infected again. I am counting the minutes to try and trying to hold on. I want to go back to work, I want to not be sick, I want to grow old (I’m just 51). I would do anything to have my health back.

  • http://xconomy J Dub

    I did a year on Peg-Intron (alph interferon 2-b). I’ve been in pain ever since. My legs have an excruciating vibration that never quits. It varies in intensity. At best it’s a very uncomfortable tremble in my lower legs. But most of the time it is much worse. Often consuming most of my entire body. Sometimes from my ribcage to my toes. My legs are also in constant pain. The vibration causes the muscles, tendons, and joints in my legs to hurt costantly, because they are always tense and trying to compensate. I’m just 58, I would also do anything to have my health back. I want my LIFE back. I have to go lay down now. Too much activity causes more pain. I wanna get out of bed, go to work. I want to go sailing again. But I doubt I ever will. Interferon screwed me up so much that IF I ever try another drug treatment and it doesn’t help me I hope it kills me. Sounds very dramatic, but that’s exactly how I feel. Depression was a battle during treatment. It’s worse now! I think about suicide. But it’s not an option, I have a family.

  • Saumitra

    Luke , you could perhaps annotate this excellent article by adding this latest – not so good news on Telaprevir http://online.wsj.com/article/BT-CO-20101221-713662.html