Update on Telaprevir trials optimistic

-------------Word from TheStreet twittered via Hep C Research and News-------------

Vertex Cures Hard-to-Treat Hep C Patients

By Adam Feuerstein 09/07/10 - 04:02 PM EDT

CAMBRIDGE, Mass. () -- Vertex Pharmaceuticals (VRTX) released new late-stage clinical data Tuesday demonstrating that 65% of hepatitis C patients whose prior therapy was unsuccessful were able to later achieve a viral cure following treatment with the company's experimental drug telaprevir plus the current standard of care.

By comparison, only 17% of these hard-to-treat hepatitis C patients were cured after being treated again with the current standard of care -- long-acting interferon plus ribavirin. The results were statistically significant.

These results come from the last of three major phase III studies of telaprevir conducted by Vertex and partner Johnson & Johnson(JNJ). Previous, positive results from the other two late-stage telaprevir studies in newly treated hepatitis C patients were released in May and August. The companies intend to seek regulatory approval for telaprevir later this year.

This last phase III study, dubbed "Realize," was set up to confirm previous, earlier findings that showed telaprevir could cure a significant number of hepatitis C patients without treatment options because they failed to respond to the current standard of care.

The Realize study enrolled 662 so-called treatment resistant hepatitis C patients split into three different groups: Those who respond to treatment but then relapse during the follow-up period; patients who partially respond to treatment but whose virus never completely disappears; and patients who never respond well to treatment at all.

Since these patients have a form of the hepatitis C virus that is more stubborn or harder to treat, Vertex extended the total treatment duration in the Realize study to 48 weeks, compared to just 24 weeks in the previous studies of newly treated patients. [Like in other studies, telaprevir was still dosed for only 12 weeks.]

The overall results showed that 65% of patients treated with telaprevir plus the standard of care achieved a cure, or sustained viral response, compared to 17% of patients in the control arm who were re-treated with just the standard of care.

Breaking the results down into the different groups, 86% of relapsers were cured after telaprevir treatment compared to 24% in the control arm.

Among partial responders, the cure rate for the telaprevir-treated patients was 57% compared to 15% for the control arm.

Finally, in the null responder patients, the most difficult to treat patients, telaprevir achieved a 31% cure rate compared to 5% for the control arm.

Results across all three patients types were statistically significant in favor of telaprevir over standard of care.

Wall Street has been waiting for the data from the Realize study, generally expecting overall cure rates for telaprevir in the 60-70% range. The data are important because the competitive race towards approval of the first new hepatitis C drug that acts directly against the virus is heating up.

Merck (MRK) is developing its own hepatitis C drug boceprevir and is the closest competitor to Vertex. In August, Merck announced results from phase III studies showing that treatment with boceprevir led to a 66% cure rate in treatment-resistant patients.

Optically, it would appear that boceprevir and telaprevir are equally effective in curing treatment-resistant patients, which would be a letdown for Vertex and its investors given that expectations have clearly favored Vertex's drug over Merck's.

However, Vertex allowed truly non-, or null, responders into the Realize study of telaprevir, which made it more difficult for the drug to prove efficacy. Merck, on the other hand, used a less stringent definition of null response that essentially helped boceprevir achieve a higher cure rate.

If null responders are removed from analysis of the Realize study, the cure rate for partial responders and relapsers to telaprevir was 78%, which is a more accurate comparison to the 66% cure rate seen in the Merck study of boceprevir.

This doesn't mean that all went swimmingly for Vertex in the Realize results. The 31% cure rate in the null responders group treated with telaprevir was lower than what Wall Street was expecting given prior results from earlier studies.

Some analysts, including Bank of America's biotech analyst (and hepatitis C axe) Rachel McMinn, were expecting to see null responder cure rates for telaprevir in the 50% range.

Vertex said that the null responders enrolled in the Realize study had higher rates of cirrhosis and high hepatitis C viral load than the other patients in the study, which could help explain why the cure rate among these patients was lower. Despite that, telaprevir still cured five times more null responders than re-treatment with the standard of care.

Likewise, the 57% cure rate for telaprevir in partial responder patients was also a bit lower than Wall Street expectations, which means the overall, high response rate to Vertex's drug was driven largely by relapsers, considered to be the easiest of the treatment-resistant patients to respond to follow-on therapy.

On the safety side of the ledger, the new telaprevir data appear to be little changed from what's been released from the previous phase III studies. Adverse events leading to patients dropping out of the study were 4% in the telaprevir arm compared to 3% in the control arm. The most common adverse events attributed to telaprevir were fatigue and rash.

Vertex intends to make a full presentation of the Realize study data at a future medical meeting or by publication in a medical journal. Both Vertex and Merck will be among the companies presenting hepatitis C drug data at the American Association for the Study of Liver Disease annual meeting at the end of October.

--Written by Adam Feuerstein in Boston

Drug competetions: Gearing up to milk the epidemic.

---As posted at the Hepatitis C Research and News Updates blog Sunday, August 15, 2010---

The Race Is On For Hepatitis C Treatment

On Friday August 13, 2010, 6:57 pm EDT

How's this for a biopharmaceutical market opportunity? Prospective patients in need: 170 million. That's 3% of the world's population.

The disease is hepatitis C, a contagious, slow-developing, blood-borne disease that can make 80% of those infected vulnerable to severe liver problems, including cirrhosis and cancer.

Hepatitis C wasn't even identified until 1987. A blood test for it became available in 1992.

Now a score of companies are racing to bring new treatments on stream. Out front are Merck (NYSE:MRK - News) with boceprevir, and a partnership of Vertex Pharmaceuticals (NMS:VRTX) and Johnson & Johnson (NYSE:JNJ - News) with telaprevir.

The market will be pretty much evenly split between the two, says Damien Conover, a strategist and senior pharmaceutical analyst at rating firm Morningstar. Telaprevir may have a slight edge, he says.

Both drugs are protease inhibitors, which prevent a virus from replicating itself. While they treat the same disease, they are different in both results and side effects.

Used on patients who have had no previous treatment, boceprevir and telaprevir beat down the hepatitis C virus to undetectable levels in 66% and 75% of patients respectively, Conover says.

Both drugs are likely to go to the Food and Drug Administration for a verdict by the end of the year. That means both could reach the market next year.

"Right now it's hard to tell who's in the lead," Conover said.

Meanwhile, Merck and Vertex-J&J appear to be competing for headlines.

A week ago, the British-based Lancet medical journal carried a Merck-funded study showing that boceprevir brought the virus down to undetectable levels in 66% of patients over 48 weeks of treatment in combination with drugs in use now.

The next day, Aug. 10, Vertex reported study results showing that some patients did so well after a 24-week course of telaprevir (plus the current drugs in use) that they got no added benefit from a 48-week course of treatment. The message: Telaprevir does the job in half the time.

Merck acquired boceprevir with its $41 billion purchase of Schering-Plough in 2009. Vertex developed telaprevir with money from J&J in return for marketing rights.

Whether one or both of the drugs get FDA approval, the hepatitis market is about to undergo a "major paradigm shift," said Steven Silver, an analyst at Standard & Poor's.

"We've gone many years without a new drug on the landscape," he said.

It's hard to know which drug will do better in real life and in the market because they have not been tested head-to-head.

That's a long-standing problem in the drug-development industry. Prospective new products are tested either against a placebo (sugar pills) or, as in the cases of boceprevir and telaprevir, against the current standard of care.

For hepatitis C, that standard is a combination of interferon and ribavirin. It's a hit-or-miss treatment.

In simple terms, ribavirin is an antiviral medication that stops the virus that causes hepatitis C from spreading. Interferon prevents viral replication in surrounding cells.

According to the National Center for Biotechnology Information, it's not known if treatment with ribavirin and interferon actually cures hepatitis C infection, prevents liver damage caused by hepatitis C or keeps hepatitis C from spreading to other people.

The standard hepatitis C treatment results in a reduction of the virus to undetectable levels in fewer than half of cases, according to WebMD (NMS:WBMD).

Boceprevir and telaprevir are protease inhibitors. In brief, they attack the hepatitis C virus itself, WebMD says.

Without head-to-head tests, with the same dosing regimen and with the same kind of patient population, it's hard for investors to figure out whether boceprevir or telaprevir will be the greater success, assuming both get FDA approval, Conover says.

But head-to-head studies "are often not in the best interest of the company," he said.

They can show one drug so superior as to make the other unmarketable. "Head-to-head studies can backfire," Conover said.

According to Silver, the investment community "is trying to ballpark the information released to date."

He sees Vertex prevailing with telaprevir: "It's poised to be the market leader."

Data collected on real world use of these drugs are still some years off.

The market will be watching boceprevir and telaprevir for the next three or four years, Silver says.

An important factor will be the success rate of the drugs on people who have previously failed to respond to the standard of care.

That's not how clinical trials are run. They are usually conducted with patients who have not had therapy, the so-called treatment-naive. Using treatment-naive patients creates a baseline but does not approximate real-life conditions.

Most people with a disease have tried one or more drugs, ratcheting up from least to most powerful and expensive.

Another real-life issue will be the side effects. Newly diagnosed patients may find the side effects of either drug, plus interferon and ribavirin, intolerable.

The most common telaprevir side effect is a rash, Stevens says.

Boceprevir's predominant side effect is anemia. That raises the prospect that another drug will need to be added to the regimen, perhaps Epogen, the anemia-fighting biologic from Amgen (NMS:AMGN).

It's available as a generic in Europe, but remains branded in the U.S.

Another reason to think telaprevir has the inside track is the likelihood that it will require a shorter period of treatment, Silver says.

"At the end of the day, this race will be data-driven," he said.

While there's been no head-to-head trial, the existing data should become available for close comparison at a meeting of the American Association for the Study of Liver Diseases in Boston starting Oct. 28.

By most counts, the global market for hepatitis C products is now $4 billion a year. According to a report from the commercial analysis firm Research & Markets, that should rise to $8.5 billion by 2016.

The reasons for the growth: the increasing number of cases and the new drugs in the pipeline that will make treatment more accessible and tolerable.

Source

Treatment Works: Telaprevir drug trials.

Vertex: telaprevir could shorten hep C treatment

Associated Press
Updated: Aug 12, 2010 10:59 AM

CAMBRIDGE, Mass. (AP) - 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.)

Boceprevir trials: New Hope for Hep C Treatment

Good news from the Indiana University School of Medicine:

New Anti-Viral Drug Shows Promise for Dramatic Improvement in Hepatitis C Treatment

August 8, 2010

 

INDIANAPOLIS -- Adding a direct acting anti-viral drug to the standard treatment regimen for hepatitis C significantly increases the cure rate in the most difficult to treat patients, according to a research report published Monday in the online edition of the journal The Lancet.

The research team, led by Paul Kwo, M.D., of Indiana University School of Medicine, reported that adding the drug nearly doubled the treatment’s effectiveness when given for 48 weeks in one treatment arm of the study.

An estimated 3.2 million Americans and 170 million people worldwide are infected with the hepatitis C virus, but many do not know it. In the United States, 70 percent of affected individuals are infected with genotype 1 hepatitis C, the most difficult to treat. Although there may be no symptoms for years, long-term infection can cause cirrhosis and the disease is a leading cause of liver cancer and liver transplantation. Hepatitis C infections occur mainly through transmission of infected blood, such as via injection drug use, and there is no vaccine.

Currently fewer than half of patients with genotype 1 hepatitis C are treated effectively by the standard combination of two drugs, peginterferon alfa-2b plus ribavirin, which is typically given for 48 weeks. The treatment can be difficult for some patients due to anemia and other side effects.

Adding the drug boceprevir increased the cure rate to as high as 75 percent in those who received 48 weeks of the three-drug combination therapy, compared to 38 percent of those in the control group, who received the standard two-drug treatment for 48 weeks, said Dr. Kwo, associate professor of medicine at the IU School of Medicine. The two-year phase 2 trial was conducted at 67 sites with 520 patients in the U.S., Canada and Europe.

In the boceprevir study, known as the SPRINT-1 trial, researchers tested several different options to evaluate the effectiveness of the combination therapy:

• To test whether the addition of boceprevir could make it possible to shorten treatment times, some patients were randomly selected to receive the three-drug combination for 28 weeks, some for 48 weeks.
• Researchers also investigated whether a 4 week lead-in with the standard two-drug combination prior to the addition of boceprevir to the treatment regime could improve sustained virologic response rates. The goal was to see if allowing the interferon and ribavirin to reach steady state levels -- which would activate the immune system and reduce virus levels -- before adding boceprevir would improve the response rates as well as reduce the virus’ ability to develop resistance to boceprevir, said Kwo.
• In another arm of the trial, researchers tested whether a lower dose of ribavirin could reduce the anemia side effects while still treating the virus effectively.

“Both 28- and 48-week boceprevir regimens significantly increased sustained virologic response  rates – which is the best definition of a cure we have – compared to the 48 week control,” said Dr. Kwo. “The 48-week treatment arm with 4 weeks of peg interferon lead-in and 44 weeks of peg interferon, ribavirin, and boceprevir led to the largest improvement over the control group ever reported. That’s very impressive.”
Boceprevir, a product of Merck & Co., is an HCV protease inhibitor – a compound designed to block a function key to viral reproduction in the cell. Boceprevir directly targets the hepatitis C virus, Kwo noted, while peginterferon and ribavirin are less specific, acting more generally to stimulate the body’s virus-fighting immune system.

The best results were reported for the 103 patients who were treated for four weeks with the standard two drug regiment, followed by 44 weeks of the three-drug regimen including boceprevir: 75 percent of these patients tested negative for evidence of the virus six months after the end of treatment. Results for the other treatment arms were:

• 67 percent of those who received the three drug regimen for 48 weeks with no lead-in treatment tested negative for the virus (103 patients).
• 56 percent of those who received the two-drug lead-in for four weeks, followed by 24 weeks of the three drug treatment tested negative for the virus (103 patients).
• 54 percent of those who received the three-drug treatment for 28 weeks with no lead-in tested negative for the virus (107 patients).
• 38 percent of the control group, who received the standard two-drug treatment for 48 weeks tested negative for the virus (104 patients).

Patients receiving the low-dose of ribavirin did not fare as well – just 36 percent were virus-free after 48 weeks of treatment.

“Based on this phase 2 study, it appears that if this drug receives final approval approximately two-thirds of patients will be able to be treated successfully with 28 weeks of treatment and one-third will need 48 weeks of treatment, though this will require confirmation from the phase 3 trials, from which preliminary results were recently released,” said Dr. Kwo.

The research was funded by Schering Corp. a division of Merck & Co., which provided assistance with the trial, data collection and analysis, and the manuscript.

FDA Considers Expanded Use of HCV Drugs

Good for all those advocates who petitioned the FDA. I'm going to drop the feds a note about this, too. If this means they can start trying to treat people with serious mental illness - who automatically get ruled out for treatment now because the drugs are so hard on the body and mind - then this is awesome. I hate it when they experiment on prisoners, but with-holding treatment is experimentation too, so I hope this at least gives some of them more options than they have now.

-----------------

HEPATITIS C NEWS

from hepcassoc.org

April 30, 2010

ROCKVILLE, Md. -- The FDA heard public testimony Friday on establishing a compassionate use program that would allow severely ill hepatitis C (HCV) patients access to investigational, direct-acting antiviral agents.

One of the current treatments for HCV -- pegylated interferon alfa-2a and ribavirin (Rebetol) -- is highly toxic with a response rate of about 50%, clinical data show. That number is much lower in real-world cases, according to a number of physicians who testified during the public hearing.

The FDA understands current treatment options are not good enough, an official said. "Current control of hepatitis C is not working," said Peter Lurie, MD, of the FDA's Office of the Commissioner.

Friday's meeting was called in response to a petition by groups seeking access to the drugs for individuals often excluded from clinical trials.

Clinical trials are only open to a small subset of real-world HCV patients, noted Diana Sylvestre, MD, who treats HCV-infected intravenous drug users in the San Francisco area. Yet, there are many HCV patients who cannot tolerate current treatments, she said.


Her patients are rarely accepted into clinical trials, she said, because of their drug use, comorbidities, and mental illnesses.

Other patient populations who might benefit from expanded access include those with cirrhosis, HIV, or hemophilia; those awaiting transplant or post-transplant patients who have a recurrence of HCV; and African Americans and Hispanics.

Several physicians urged special consideration for minority patients, who are disproportionately left out of clinical trials. A recent study confirmed that members of ethnic minorities do not fare as well as expected with current HCV treatments.

The FDA instituted compassionate use programs in the 1970s and such drugs as trastuzumab (Herceptin), bevacizumab (Avastin), and erlotinib (Tarceva) have all been made available before formal FDA approval under an expanded access protocol.

One major expanded access program involved breakthrough HIV therapies in the '90s. "Anecdotally, the results were so striking," said Jeffrey Murray, MD, deputy director of the FDA's antiviral products division. "They did save lives."

Murray noted that the FDA is working on a guidance document on the use of direct-acting antiviral agents, which should be released sometime this year.

If approved, an expanded access program could be applied to several novel HCV treatments currently in clinical trials.

One of the most advanced is the protease inhibitor telaprevir from Vertex and Johnson & Johnson.

Results from a phase II trial showed that when telaprevir was added to pegylated interferon alfa-2a and ribavirin among patients who hadn't responded to treatment, the virus was significantly more likely to be eradicated.