August 10, 2010

Vertex Releases Results of Phase 3 ILLUMINATE Study

Telaprevir-Based Regimen as Good for Hep C Over 24 Weeks as 48 Weeks

August 10, 2010

A treatment regimen containing the experimental hepatitis C virus (HCV) antiviral telaprevir can cure HCV after 24 weeks of treatment—without requiring a full 48-week course of therapy—in people with HCV genotype 1 who have undetectable virus levels after 4 and 12 weeks of therapy. These early results from a clinical trial conducted by Vertex Pharmaceuticals were reported in a press release from the company.

Telaprevir is a member of a new class of HCV therapies called protease inhibitors. Studies suggest that telaprevir, when combined with the standard drugs pegylated interferon and ribavirin, can increase success rates by 50 percent or more. Treatment success, called a sustained virological response—or SVR—means achieving and maintaining undetectable HCV levels for six months after completing a course of HCV treatment.

Results from a Phase III clinical trial called ADVANCE suggest that telaprevir works well for patients with HCV genotype 1, which is the most common yet difficult-to-treat form of HCV in the United States. Whereas patients with HCV genotype 1 typically require 48 weeks of treatment, ADVANCE suggested that combining telaprevir with standard therapy for the first 12 weeks of treatment increased the percentage of people with undetectable genotype 1 HCV levels after 4 and 12 weeks, compared with standard therapy alone. In these patients, dubbed extended rapid virologic responders (eRVRs), all drugs could be stopped after just 24 weeks without jeopardizing the likelihood of an SVR.

As encouraging as these results were, researchers and advocates remained skeptical. In turn, Vertex’s researchers designed a second Phase III study, called ILLUMINATE. In that study, Kenneth Sherman, MD, PhD—from the University of Cincinnati College of Medicine and a principal investigator of the trial—and his colleagues enrolled 500 people who had HCV genotype 1, none of whom had been treated previously, and randomized them to either 24 or 48 weeks of HCV treatment.

All of the participants in ILLUMINATE took standard HCV treatment—pegylated interferon plus ribavirin—combined with telaprevir for 12 weeks. After 12 weeks, people stopped the telaprevir and continued on therapy for an additional 12 weeks (24 weeks of treatment in all).

Patients who achieved an eRVR—undetectable HCV levels after 4 and 12 weeks of therapy—were then randomized to either stop therapy altogether after 24 weeks or continue treatment for a total of 48 weeks. Patients who did not have a eRVR were automatically continued on standard therapy for 48 weeks.

The analysis described in the Vertex press release involved only those who achieved an eRVR and were randomized to either discontinue or remain on therapy after 24 weeks. Full results from the study, including those who did not achieved an eRVR, will be reported at a later date.

Overall, Sherman and his colleagues found that eRVRs who stayed on treatment for 48 weeks had no more chance of treatment success than those who completed only 24 weeks of treatment. In all, 92 percent of eRVRs who took 24 weeks of treatment were cured of HCV, compared with 88 percent who took treatment for 48 weeks.

The percentage of people who had undetectable HCV levels at the end of treatment but whose HCV later returned (relapsers) was 5.9 percent in eRVRs on 24 weeks of treatment compared with 1.9 percent of those on 48 weeks of treatment.

The overall number of people who achieved an HCV genotype 1 cure, regardless of their early virologic response, was also relatively high, at 72 percent.

“The viral cure rates seen in ILLUMINATE showed that there was no benefit to extending telaprevir-based therapy to 48 weeks for the majority of people,” Sherman said. “Patients who had a rapid response to telaprevir-based regimens at weeks four and 12 had a high likelihood of achieving a cure with 24 weeks of total treatment, which may provide important information to motivate people to continue therapy.”

Thus far, studies have taken place only in HCV monoinfected individuals—people infected only with HCV, not coinfected with HIV and HCV. Trials in HIV-coinfected people are planned and should get underway in the coming months. In the meantime, however, good results in monoinfected people offer real hope to people who are coinfected. Facing the prospect of 48 weeks of current HCV treatment—which has significant side effects and only works 25 percent of the time—many coinfected people feel conflicted about starting therapy. A new treatment, however, that offers the chance of better results in half the time would represent a significant advance.

Search: Vertex, telaprevir, hepatitis C virus, Hep C, HCV, sustained virological response, ADVANCE, ILLUMINATE

Vertex: telaprevir could shorten hep C treatment
(AP) – 1 hour ago

CAMBRIDGE, Mass. — Vertex Pharmaceuticals Inc. said Tuesday that a study showed some patients who take its hepatitis C drug candidate telaprevir may be able to complete their treatment sooner.

Vertex said patients who responded quickly to treatment with telaprevir had better results after 24 weeks of therapy than after 48 weeks. The company said that shows a 24-week regimen including telaprevir can be an effective treatment for the disease.

Vertex highlighted results for patients who responded well to telaprevir, as they had undetectable levels of the hepatitis C virus after 4 weeks and 12 weeks of treatment. Treatment in the study included 12 weeks of telaprevir in combination with two older drugs, pegylated interferon and ribavirin. That was followed by additional treatment with pegylated interferon and ribavirin alone.

The patients who had undetectable virus levels after 4 weeks and 12 weeks were treated with pegylated interferon and ribavirin for either 12 more weeks or 36 more weeks. Of the patients who were treated for an additional 12 weeks — making 24 weeks of therapy in total — Vertex said 92 percent had undetectable levels of the hepatitis C virus. It said 88 percent of the patients who received 48 weeks of treatment had undetectable virus levels.

Patients' virus levels were measured 24 weeks after the end of their treatment.

The clinical trial was called ILLUMINATE. Patients who did not have a quick response to telaprevir were given pegylated interferon and ribavirin alone for 48 weeks.

The company plans to file for Food and Drug Administration approval of telaprevir in the fourth quarter. The drug is seen as a potential billion-seller for Vertex.

The most common side effects of telaprevir treatment were fatigue, itching, nausea, anemia, rash, and headache. Vertex said most of those side effects were mild or moderate.

In morning trading, Vertex shares fell 75 cents, or 2 percent, to $36.25.

(This version CORRECTS details on the design of the trial.)
Copyright © 2010 The Associated Press. All rights reserved.

AUGUST 10, 2010, 10:34 A.M. ET.
Vertex Reports Success In Second Major Hepatitis Drug Study
By Thomas Gryta Of DOW JONES NEWSWIRES NEW YORK (Dow Jones)--Vertex Pharmaceuticals Inc. (VRTX) reported the success of the second of three key late-stage studies of hepatitis-C treatment, telaprevir, essentially curing 72% of patients using the drug.
The study, a supplement to the larger studies intended to support teleprevir's approval, showed there was no benefit to extending treatment to 48 weeks from 24 weeks in the majority of patients. The results are notable because they improve the sustained viral response, or SVR, which is essentially a cure for the liver disease, and shorten the length of therapy for most patients.

Vertex shares recently slid 2.3% to $36.14 on a down day for the market so far. The study's success was largely expected as investors watch for the data of all three studies, the last of which is coming in September, to gauge telaprevir's place in a competitive hepatitis C market. Vertex's shares, up 11% since late July, rose 2.3% in the wake of news of the first study's success in May.

Hepatitis C is a blood-transmitted virus that causes liver inflammation and can lead to cirrhosis, cancer and liver failure.

The current standard therapy, a combination of pegylated-interferon injections and ribavirin pills over 48 weeks, achieves an SVR in up to about 50% of patients, according to the Centers for Disease Control.

The latest study, called Illuminate, included 540 people infected with the genotype 1 strain of the virus, its most common form in the U.S. and Europe.

The trial is considered supplemental, as it is a single-armed study with no patient group taking a placebo, as they do in the other late-stage studies.

In the Illuminate trial, all patients received telaprevir for 12 weeks with standard therapy, with interferon and ribavirin continuing for another 12 weeks.

The results showed a cure for 72% of all patients in the trial. For the 65% of patients showing an early response to the drug, those on a 24-week regimen showed a 92% SVR rate and a 48-week group achieved SVR in 88% of patients. The relapse rate in the short regimen was 5.7%, compared with 1.9% in the longer group.

Vertex plans to complete its marketing application to the Food and Drug Administration before the end of the year. The company plans to market the drug itself in North America, while Johnson & Johnson (JNJ) will help sell telaprevir overseas, with Mitsubishi Tanabe Pharma Corp. (4508.TO) holding rights in Japan and some other Asian countries.

Vertex said the side-effect profile in telaprevir's latest trial was consistent with that of earlier studies, including fatigue, itching, nausea, and anemia. Side effects led to discontinuation of therapy during the first 12 weeks in 6.9% of patients.

Last week, Merck & Co. (MRK) reported positive results from two large studies of its own Hepatitis therapy, boceprevir, which it plans to submit for regulatory approval in the U.S. and Europe this year.

At the time, analysts perceived the telaprevir data as more impressive.

Both the Merck and Vertex drugs are known as protease inhibitors, which are designed to block an enzyme that helps hepatitis C virus replicate. Standard treatment is a combination of the drug pegylated interferon and ribavirin. The hope is that protease inhibitors can improve cure rates versus standard treatment, and potentially shorten the duration of treatment.

Many other companies are developing hepatitis C treatments, including Bristol-Myers Squibb Co. (BMY), Gilead Sciences Inc. (GILD) and Roche Holding AG (RHHBY, ROG.VX).

-By Thomas Gryta, Dow Jones Newswires; 212-416-2169;

Vertex hep C drug works in 24 weeks for many -study

By Bill Berkrot
Tue Aug 10, 2010 7:07pm IST

NEW YORK (Reuters) - A study of Vertex Pharmaceuticals Inc's high profile experimental hepatitis C drug showed that the overwhelming majority of previously untreated patients who respond early to telaprevir can be cured in half the time of current therapy.

Of the so-called rapid viral responders, 92 percent of patients who received a total of 24 weeks of therapy with telaprevir plus the standard treatment of pegylated interferon and ribavirin achieved sustained virologic response, or SVR, which is considered tantamount to a cure.

The overall cure rate for all telaprevir patients was 72 percent, a touch below the 75 percent seen in an earlier Phase III trial. But most patients in whom the virus is cleared early may be able to complete treatment in half the time of current tough to tolerate therapy, the data showed.

New data on the drug, which some analysts believe could eventually capture annual sales of more than $4 billion if it is approved, lifted shares of Vertex 3.7 percent to $38.40 in premarket trading on Nasdaq.

The lofty hopes for telaprevir are based on its ability to cure a far higher percentage of patients than standard drugs and its potential to cut treatment duration.

In the earlier Phase III trial of previously untreated patients interferon and ribavirin without telaprevir cured only 44 percent of patients. Those drugs must be taken for 48 weeks and often cause debilitating flu-like symptoms, leading many patients to discontinue their use.

The latest late-stage trial separated out patients in whom the virus was undetectable at both week 4 and 12 of treatment with the three-drug combination to see if there was any advantage to extending therapy with standard drugs beyond 24 weeks to the full 48 weeks in those patients.

Sixty-five percent of the 540 trial participants fell into the rapid responder category. In all cases telaprevir was part of the regimen for the first 12 weeks.

Among those rapid responders, there was an 88 percent cure rate with the full 48 weeks -- slightly less than with 24 weeks. But there was a lower relapse rate with the 48-week group -- 1.9 percent versus 5.7 percent with the 24-week regimen, or 3 patients versus 9.

"Patients who had a rapid response to telaprevir-based regimens at weeks 4 and 12 had a high likelihood of achieving a cure with 24 weeks of total treatment, which may provide important information to motivate people to continue therapy," Dr Kenneth Sherman, principal investigator of the trial, said in a statement.

The company next month is expected to release data from one more Phase III study, this time in much tougher-to-treat patients who failed to be helped by prior therapy with standard drugs.

The three late-stage trials will form the basis for Vertex's application seeking approval of the drug that it plans to file with the U.S. Food and Drug Administration by the end of the year.

Telaprevir, from a new class of hepatitis C treatments, is expected to compete with a similar drug being developed by Merck & Co called boceprevir. But analysts have been virtually unanimous in their belief that telaprevir is the better of the two drugs.

Boceprevir led to an overall cure rate of 66 percent in a study recently released by Merck.

The safety and tolerability of telaprevir in the latest Vertex trial was similar to what was seen in the earlier late-stage study, the company said.

Adverse events, including rash and anemia, led to a discontinuation rate of nearly 7 percent of patients.

(Reporting by Bill Berkrot; Editing by Gary Hill, Dave Zimmerman)


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