An article appearing on Pharmiweb about the approval of Telaprevir and Boceprevir, but also comments on alisporivir, also known as DEB025 which Novartis licensed from fellow Swiss firm Debiopharm in February 2009.
THE Food and Drug Administration (FDA) has approved Vertex Pharmaceuticals Inc.'s (VRTX) hepatitis C drug telaprevir and Merck’s hepatitis C drug, boceprevir.
Both drugs are protease inhibitors (PIs) and are designed to block an enzyme that helps the hepatitis C virus replicate. Hepatitis C is a liver disease caused by infection with the hepatitis C virus, which is transmitted through contaminated blood. The infection can cause liver failure and liver cancer.
The move follows the presentation and publication of new data on the drugs at the recent annual meeting of the European Association for the Study of Liver Disease (EASL) held in Berlin. Also presented at the meeting was data on Novartis' novel investigational oral agent alisporivir. This data was described as “fantastic” by EASL vice secretary Mark Thursz, professor of hepatology at Imperial College, London, while Robert Flisiak from the Medical University of Bialystok, Poland, told the congress as he presented the data: “This novel agent has the potential to be an important component of future hepatitis C treatment.” The availability of novel agents such as alisporivir and the protease inhibitors marks a new era in the treatment of hepatitis C infection. More than 30 potential hepatitis C agents are currently in R&D pipelines. Professor Thursz said that the new PIs offered unprecedented levels of sustained virological response and would be used initially with the current standard of care, pegylated interferon-alpha plus ribavirin. However, with so many potential novel treatments for hepatitis C on the horizon, he envisaged a time when standard of care for hepatitis C would be an interferon-free regimen. Boehringer’s HCV polymerase inhibitor BI 207127 has been fast-tracked by the FDA in combination whilst Bristol-Myers Squibb is trialling its PI, BMS 650032, in combination with the NS5A inhibitor BMS 790052.
Novartis’ alisporivir shows significant promise if its phase II data from the ESSENTIAL study, presented at EASL, is repeated in a phase III trial, which is now underway. The ESSENTIAL study involved 300 previously untreated patients infected with genotype 1 HCV. Of those treated with alisporivir, plus standard of care (pegylated-interferon alfa 2a/ribavirin), 76% achieved superior viral cure compared to 55% of patients on standard care alone 24 weeks after stopping treatment.
The study’s principal investigator, Stefan Zeuzem from Goethe University Hospital in Frankfurt, said: “Hepatitis C is difficult to treat and current therapies are effective only in about half of patients with the most prevalent genotype. These results are exciting because a large majority of patients achieved sustained viral response with alisporivir.”
Alisporivir is the first in a new class of drugs called cyclophilin inhibitors. Unlike other compounds in development that target the hepatitis C virus directly, alispirovir, targets host proteins that the hepatitis C virus uses for replication. A Phase IIb trial looking at the potential of the agent in HCV patients with genotypes 2 and 3 is also underway. The host proteins are needed for replication in all types of HCV infection so there is potential for the agent to have broad activity; there are six variations of HCV.
An international Phase III study is evaluating the efficacy and safety of alisporivir combined with standard care in previously untreated HCV G1 patients. The Phase II study showed that serious adverse events occurred in 6.9% of patients treated with alispirovir and standard care compared to 5.5% of patients treated with standard care alone. Prof Flisiak reported a higher rate of bilirubin (32.9% versus 1.4% in the alisporivir-treated group compared to standard care alone) but this was transient and reversible and associated with the initial loading dose. Final data from the Phase III ESSENTIAL-2 is expected in March 2013.
Novartis medical director Nikolai Naoumov said: “The data is very encouraging because it has produced a significant response in the most common form of HCV which can be very difficult to treat and with a reasonable safety profile. If the results of Phase III and other studies are also encouraging, this agent could offer a paradigm shift in clinical practice by being able to treat a number of genotypes and patients who have not responded to standard care.” Novartis in-licensed alisporivir, also known as DEB025, from fellow Swiss firm Debiopharm in February 2009.
Read more: http://www.pharmiweb.com/pressreleases/pressrel.asp?ROW_ID=40176#ixzz1Lo0stbq3
Original article here: http://www.pharmiweb.com/pressreleases/pressrel.asp?ROW_ID=40176
Sunday, May 8, 2011
HIV Physicians Are Cautiously Optimistic About Boceprevir, Telaprevir For HIV-HCV Co-Infected Patients
Courtney McQueen from The AIDS Beacon, interviews Dr. Kenneth Mayer from Brown University's HIV program and Dr. Bruce Bacon ce Bacon,co-director of the Liver Center at St. Louis University Medical School on the use of Telaprevir and Boceprevir in co-infected patient. It appears both are cautiously hopeful about the use of either drugs in the co-infected setting, but need to fully understand the ramifications of the final data set, that should arrive in June 2012 for telaprevir and November 2012 for boceprevir. The largest cause for caution are the known drug interactions with many of the currently marketed antiretrovirals
HIV Physicians Are Cautiously Optimistic About Boceprevir, Telaprevir For HIV-HCV Co-Infected Patients
By Courtney McQueen
Published: May 6, 2011 6:02 pm
Last week an advisory panel to the U.S. Food and Drug Administration recommended that boceprevir and telaprevir be approved for the treatment of hepatitis C. For people with HIV and hepatitis C co-infection, the new drugs are an exciting development; however, a number of studies still need to be completed before the drugs are considered for people with HIV.
“It has the potential to revolutionize care, but I think it’s just the beginning of the journey,” said Dr. Kenneth Mayer, a professor of medicine at Brown University, director of the Brown University AIDS Program, and medical research director at Fenway Community Health. Dr. Mayer was not involved with development of either of the drugs.
Dr. Mayer, who has been seeing HIV and AIDS patients since the beginning of the epidemic, thought the early results for both drugs are promising. However, he also thought a lot more research needs to be done before clinicians can feel comfortable prescribing the drugs to people with HIV.
“The vast majority of the studies so far are in mono-infected individuals [people with hepatitis C only], so I think there’s a bunch of questions that have to be answered before we’re sure of how to use these drugs best for people with HIV,” he said.
If the Food and Drug Administration (FDA) approves the drugs, they could be available to patients as soon as late May. Although the FDA is not required to follow the recommendations of its advisory committees, it usually does.
For People With HIV, Boceprevir And Telaprevir Clinical Trials Are Still In Early Stages
The approval recommendations from last week are based on Phase 3 clinical trials in people infected only with hepatitis C virus (HCV). The trials showed that adding boceprevir or telaprevir to standard HCV treatment raised cure rates from about 40 to 45 percent to about 65 to 80 percent.
Standard HCV treatment consists of 48 weeks of ribavirin (Rebetol, Copegus) plus Pegasys (pegylated interferon alfa-2a) or PegIntron (pegylated interferon alfa-2b). Typically, standard HCV treatment is less effective in people who are also infected with HIV (see related AIDS Beacon news).
For people with HIV, the benefits of the new drugs are not clear yet. Both drugs are currently in Phase 2 clinical trials for people who are co-infected with HIV and HCV, with estimated trial completion dates of June 2012 for telaprevir and November 2012 for boceprevir.
Dr. Bruce Bacon, a professor of internal medicine and co-director of the Liver Center at St. Louis University Medical School, was involved in clinical trials for both drugs and expressed optimism about their success in co-infected patients.
“Definitely the cure rates, or sustained virologic response, for co-infected patients will be significantly improved with either boceprevir or telaprevir. How much they will be improved, I don’t know yet,” he said.
Preliminary results for telaprevir were presented in March at the Conference on Retroviruses and Opportunistic Infections (see related AIDS Beacon news). Results at that time were promising; 70 percent of HIV-HCV patients receiving telaprevir in addition to standard therapy of ribavirin and Pegasys had undetectable HCV levels after four weeks, compared to 5 percent of patients receiving the placebo plus standard therapy.
Among the participants who received telaprevir for 12 weeks, 68 percent had undetectable HCV levels, compared to 14 percent of participants receiving ribavirin plus Pegasys alone. However, not all participants had reached 12 weeks of treatment by the time of the analysis.
Additionally, overall hepatitis C cure rates were not yet available. Clinicians consider a patient to be cured of hepatitis C if the virus remains undetectable for 24 weeks after stopping treatment (called a sustained virologic response).
Dr. Bacon stated that the telaprevir results should be taken with caution. “That’s pretty early data. I think it’s probably a little too early to know the significance of [the telaprevir results],” he said.
Results for boceprevir in people who are HIV-HCV co-infected are not yet available.
For people with HIV-HCV co-infection, the lack of definitive results means that some patients may need to decide whether to take the drugs when they become available, or wait until the clinical trials are complete and physicians have more information on the drugs’ efficacy and safety in people with HIV.
“If a person is not in acute need of treatment, it may be prudent to wait, to know how to best manage [treatment],” said Dr. Mayer.
“The initial guidelines will not recommend these drugs for co-infected people until there is more data, so there would also be a question of whether third party payers or insurers would reimburse for the cost of the medications, and I’m sure that the cost of the medications would be considerable,” he added.
Dr. Bacon stated that he was likely to start prescribing the drugs without waiting for all of the clinical trial results. “I have a large number of co-infected patients who are waiting for treatment, and I’m probably not going to wait until the results of all the studies are done. But I do need to make sure that I find out about the drug-drug interaction issues,” he said.
More Data Needed On Drug Interactions, Safety In People With HIV
Both Dr. Mayer and Dr. Bacon agreed that one of the main concerns for people with HIV will be the safety of the drugs and whether they interact with HIV medications.
“I’m hoping that there will be a very robust program of research for dually infected individuals, so we can get a better sense of the expanded safety profile of these drugs,” said Dr. Mayer.
Both boceprevir and telaprevir have associated side effects, such as anemia and rash (see related AIDS Beacon news). The Phase 2 trials in co-infected people should demonstrate whether these side effects are more common or more severe in people with HIV.
In addition, the clinical trials that are underway for both drugs will monitor how they interact with common HIV antiretrovirals. For example, researchers will test whether the hepatitis C drugs affect the concentrations of antiretrovirals in the bloodstream – either decreasing them, which would make them less effective against HIV, or increasing them, which could cause greater side effects.
They will also test whether the antiretrovirals, in turn, affect the hepatitis C drugs and their efficacy. If drug interactions are found, dosages of either the hepatitis C drugs or certain antiretrovirals may need to be adjusted for people with HIV.
For telaprevir, there are some preliminary indications that there might be interactions with certain antiretrovirals, namely protease inhibitors boosted with Norvir (ritonavir). It is not clear yet whether these will require dosage adjustments of either telaprevir or the protease inhibitors in patients taking these drugs.
No information is available yet on drug interactions for boceprevir.
People With HIV Should Get Tested – And Retested – For Hepatitis C
With the two new drugs potentially available in the near future, both physicians urged people with HIV to get tested for HCV so they can start treatment if necessary.
“This underscores the importance of everybody who’s HIV infected to know their hepatitis C status. If somebody has engaged in any behaviors that might put them at risk for acquiring hepatitis C, they should be retested,” said Dr. Mayer.
“Even if somebody is not going to start these medications tomorrow, we are getting into the mode where, fairly soon, we’ll be able to start treating hepatitis C earlier,” he added.
Hepatitis C is spread in much the same way as HIV – unprotected sexual intercourse, sharing of needles, and other exposures to infected bodily fluids.
Dr. Bacon said patients who are co-infected should not avoid treatment.
“If they do know that they’re co-infected, they should know that there’s something that will be better than what there used to be. They ought to see a specialist who is knowledgeable about [the new drugs], and they ought to be treated,” said Dr. Bacon.
“I think it’s a new era for hepatitis C patients, and it will be a new era for co-infected patients as well,” he added.
Next Steps For Hepatitis C Treatment
Researchers have already begun to discuss the next phases of hepatitis C treatment. Both Dr. Mayer and Dr. Bacon were optimistic about the future for people with hepatitis C and HIV-HCV co-infection.
“Hopefully in the next few years we’ll be in the position to have a lot of different choices, much in the same way that we have for HIV,” said Dr. Mayer.
Dr. Bacon agreed. “Most people feel that there will be new regimens that are going to be used, and both telaprevir and boceprevir, as first generation protease inhibitors, will be replaced by second and third generation drugs and different regimens. Hopefully interferon-free regimens,” he said.
Interferon (Pegasys or PegIntron), which is part of the current standard treatment regimen for hepatitis C, is difficult to take (it must be injected, usually once a week) and is associated with many side effects.
“I think we’re within a couple of years of having large studies with non-interferon based treatment that will be successful,” said Dr. Bacon.
Original article: http://www.aidsbeacon.com/news/2011/05/06/hiv-aids-physicians-are-cautiously-optimistic-about-boceprevir-telaprevir-for-hiv-hcv-co-infected-patients/
HIV Physicians Are Cautiously Optimistic About Boceprevir, Telaprevir For HIV-HCV Co-Infected Patients
By Courtney McQueen
Published: May 6, 2011 6:02 pm
Last week an advisory panel to the U.S. Food and Drug Administration recommended that boceprevir and telaprevir be approved for the treatment of hepatitis C. For people with HIV and hepatitis C co-infection, the new drugs are an exciting development; however, a number of studies still need to be completed before the drugs are considered for people with HIV.
“It has the potential to revolutionize care, but I think it’s just the beginning of the journey,” said Dr. Kenneth Mayer, a professor of medicine at Brown University, director of the Brown University AIDS Program, and medical research director at Fenway Community Health. Dr. Mayer was not involved with development of either of the drugs.
Dr. Mayer, who has been seeing HIV and AIDS patients since the beginning of the epidemic, thought the early results for both drugs are promising. However, he also thought a lot more research needs to be done before clinicians can feel comfortable prescribing the drugs to people with HIV.
“The vast majority of the studies so far are in mono-infected individuals [people with hepatitis C only], so I think there’s a bunch of questions that have to be answered before we’re sure of how to use these drugs best for people with HIV,” he said.
If the Food and Drug Administration (FDA) approves the drugs, they could be available to patients as soon as late May. Although the FDA is not required to follow the recommendations of its advisory committees, it usually does.
For People With HIV, Boceprevir And Telaprevir Clinical Trials Are Still In Early Stages
The approval recommendations from last week are based on Phase 3 clinical trials in people infected only with hepatitis C virus (HCV). The trials showed that adding boceprevir or telaprevir to standard HCV treatment raised cure rates from about 40 to 45 percent to about 65 to 80 percent.
Standard HCV treatment consists of 48 weeks of ribavirin (Rebetol, Copegus) plus Pegasys (pegylated interferon alfa-2a) or PegIntron (pegylated interferon alfa-2b). Typically, standard HCV treatment is less effective in people who are also infected with HIV (see related AIDS Beacon news).
For people with HIV, the benefits of the new drugs are not clear yet. Both drugs are currently in Phase 2 clinical trials for people who are co-infected with HIV and HCV, with estimated trial completion dates of June 2012 for telaprevir and November 2012 for boceprevir.
Dr. Bruce Bacon, a professor of internal medicine and co-director of the Liver Center at St. Louis University Medical School, was involved in clinical trials for both drugs and expressed optimism about their success in co-infected patients.
“Definitely the cure rates, or sustained virologic response, for co-infected patients will be significantly improved with either boceprevir or telaprevir. How much they will be improved, I don’t know yet,” he said.
Preliminary results for telaprevir were presented in March at the Conference on Retroviruses and Opportunistic Infections (see related AIDS Beacon news). Results at that time were promising; 70 percent of HIV-HCV patients receiving telaprevir in addition to standard therapy of ribavirin and Pegasys had undetectable HCV levels after four weeks, compared to 5 percent of patients receiving the placebo plus standard therapy.
Among the participants who received telaprevir for 12 weeks, 68 percent had undetectable HCV levels, compared to 14 percent of participants receiving ribavirin plus Pegasys alone. However, not all participants had reached 12 weeks of treatment by the time of the analysis.
Additionally, overall hepatitis C cure rates were not yet available. Clinicians consider a patient to be cured of hepatitis C if the virus remains undetectable for 24 weeks after stopping treatment (called a sustained virologic response).
Dr. Bacon stated that the telaprevir results should be taken with caution. “That’s pretty early data. I think it’s probably a little too early to know the significance of [the telaprevir results],” he said.
Results for boceprevir in people who are HIV-HCV co-infected are not yet available.
For people with HIV-HCV co-infection, the lack of definitive results means that some patients may need to decide whether to take the drugs when they become available, or wait until the clinical trials are complete and physicians have more information on the drugs’ efficacy and safety in people with HIV.
“If a person is not in acute need of treatment, it may be prudent to wait, to know how to best manage [treatment],” said Dr. Mayer.
“The initial guidelines will not recommend these drugs for co-infected people until there is more data, so there would also be a question of whether third party payers or insurers would reimburse for the cost of the medications, and I’m sure that the cost of the medications would be considerable,” he added.
Dr. Bacon stated that he was likely to start prescribing the drugs without waiting for all of the clinical trial results. “I have a large number of co-infected patients who are waiting for treatment, and I’m probably not going to wait until the results of all the studies are done. But I do need to make sure that I find out about the drug-drug interaction issues,” he said.
More Data Needed On Drug Interactions, Safety In People With HIV
Both Dr. Mayer and Dr. Bacon agreed that one of the main concerns for people with HIV will be the safety of the drugs and whether they interact with HIV medications.
“I’m hoping that there will be a very robust program of research for dually infected individuals, so we can get a better sense of the expanded safety profile of these drugs,” said Dr. Mayer.
Both boceprevir and telaprevir have associated side effects, such as anemia and rash (see related AIDS Beacon news). The Phase 2 trials in co-infected people should demonstrate whether these side effects are more common or more severe in people with HIV.
In addition, the clinical trials that are underway for both drugs will monitor how they interact with common HIV antiretrovirals. For example, researchers will test whether the hepatitis C drugs affect the concentrations of antiretrovirals in the bloodstream – either decreasing them, which would make them less effective against HIV, or increasing them, which could cause greater side effects.
They will also test whether the antiretrovirals, in turn, affect the hepatitis C drugs and their efficacy. If drug interactions are found, dosages of either the hepatitis C drugs or certain antiretrovirals may need to be adjusted for people with HIV.
For telaprevir, there are some preliminary indications that there might be interactions with certain antiretrovirals, namely protease inhibitors boosted with Norvir (ritonavir). It is not clear yet whether these will require dosage adjustments of either telaprevir or the protease inhibitors in patients taking these drugs.
No information is available yet on drug interactions for boceprevir.
People With HIV Should Get Tested – And Retested – For Hepatitis C
With the two new drugs potentially available in the near future, both physicians urged people with HIV to get tested for HCV so they can start treatment if necessary.
“This underscores the importance of everybody who’s HIV infected to know their hepatitis C status. If somebody has engaged in any behaviors that might put them at risk for acquiring hepatitis C, they should be retested,” said Dr. Mayer.
“Even if somebody is not going to start these medications tomorrow, we are getting into the mode where, fairly soon, we’ll be able to start treating hepatitis C earlier,” he added.
Hepatitis C is spread in much the same way as HIV – unprotected sexual intercourse, sharing of needles, and other exposures to infected bodily fluids.
Dr. Bacon said patients who are co-infected should not avoid treatment.
“If they do know that they’re co-infected, they should know that there’s something that will be better than what there used to be. They ought to see a specialist who is knowledgeable about [the new drugs], and they ought to be treated,” said Dr. Bacon.
“I think it’s a new era for hepatitis C patients, and it will be a new era for co-infected patients as well,” he added.
Next Steps For Hepatitis C Treatment
Researchers have already begun to discuss the next phases of hepatitis C treatment. Both Dr. Mayer and Dr. Bacon were optimistic about the future for people with hepatitis C and HIV-HCV co-infection.
“Hopefully in the next few years we’ll be in the position to have a lot of different choices, much in the same way that we have for HIV,” said Dr. Mayer.
Dr. Bacon agreed. “Most people feel that there will be new regimens that are going to be used, and both telaprevir and boceprevir, as first generation protease inhibitors, will be replaced by second and third generation drugs and different regimens. Hopefully interferon-free regimens,” he said.
Interferon (Pegasys or PegIntron), which is part of the current standard treatment regimen for hepatitis C, is difficult to take (it must be injected, usually once a week) and is associated with many side effects.
“I think we’re within a couple of years of having large studies with non-interferon based treatment that will be successful,” said Dr. Bacon.
Original article: http://www.aidsbeacon.com/news/2011/05/06/hiv-aids-physicians-are-cautiously-optimistic-about-boceprevir-telaprevir-for-hiv-hcv-co-infected-patients/
Friday, April 29, 2011
FDA advisory panel gives thumbs up to Vertex's Telaprevir...
FDA backs Vertex hepatitis drug efficacy, shares jump
Tue, Apr 26 2011
By Lisa Richwine
WASHINGTON (Reuters) - A hepatitis C drug from Vertex Pharmaceuticals Inc cured more patients than previously reported, U.S. health reviewers said, boosting the approval chances for a pill expected to transform treatment of the liver-destroying disease that afflicts millions.
Vertex shares rose 12 percent to their highest level in a decade after comments from Food and Drug Administration staff on Tuesday that analysts said favored the medicine's approval.
Shares of Merck, whose rival hepatitis C treatment also faces an FDA panel's review this week, rose 2.2 percent.
Both medicines are expected to reap more than $1 billion in sales if approved after demonstrating an ability to cure far more patients than current standard drugs, in some cases in half the time.
Vertex's telaprevir eliminated the hepatitis C virus in 79 percent of newly treated patients, FDA reviewers said. That was higher than the 75 percent Vertex reported earlier because the FDA used a different cure rate calculation.
Analysts said the higher effectiveness, plus few FDA safety concerns, meant an advisory panel would likely recommend approval of the drug on Thursday.
"We now expect telaprevir to get a relatively clean recommendation (and hence approval) with no significant exclusions, restrictions, warnings or caveats," Sanford Bernstein analyst Geoffrey Porges said in a research note.
Current therapies require almost a year of treatment and often cause flu-like symptoms that are tough to tolerate, with only about a 40 percent success rate. Both of the new medicines work by blocking a protein called protease that the virus needs to replicate.
WAITING FOR TREATMENT
Doctors say tens of thousands of patients have been delaying treatment in anticipation of the new anti-virals, which still must be taken in combination with the older drugs ribavirin and interferon.
Hepatitis C is a bloodborne liver disease that can lead to chronic liver problems, liver cancer, cirrhosis and death. It is spread mainly through reuse of needles such as those used for illegal drugs and tattoos, or through blood transfusions before 1992 when screening began. About 3.2 million Americans and 170 million people worldwide have the disease.
Analysts widely expect the Vertex pill to dominate the market with its greater effectiveness. Telaprevir's 79 percent success rate compares with up to 66 percent for Merck's drug, boceprevir, in previously untreated patients. It also had a higher cure rate than the Merck drug in patients who had failed to be helped by prior therapy.
"Overall, the FDA review team's independent analyses confirmed the applicant's primary efficacy findings," FDA staff said in a summary prepared for the advisory panel of outside experts.
The FDA reviewers said they would ask the panel to discuss rashes and anemia seen in clinical trials of telaprevir. Those issues were known and analysts do not expect them to derail the drug's approval.
An FDA panel will review the Merck drug on Wednesday. In documents released on Monday, agency reviewers said Merck's drug appeared effective but highlighted anemia and other safety issues for panel discussion.
The FDA usually approves medicines that win advisory panel backing. An approval decision for either drug could come as early as May.
(Additional reporting by Toni Clarke and Bill Berkrot, editing by Michele Gershberg, Gerald E. McCormick, Derek Caney and Bernard Orr)
Tue, Apr 26 2011
By Lisa Richwine
WASHINGTON (Reuters) - A hepatitis C drug from Vertex Pharmaceuticals Inc cured more patients than previously reported, U.S. health reviewers said, boosting the approval chances for a pill expected to transform treatment of the liver-destroying disease that afflicts millions.
Vertex shares rose 12 percent to their highest level in a decade after comments from Food and Drug Administration staff on Tuesday that analysts said favored the medicine's approval.
Shares of Merck, whose rival hepatitis C treatment also faces an FDA panel's review this week, rose 2.2 percent.
Both medicines are expected to reap more than $1 billion in sales if approved after demonstrating an ability to cure far more patients than current standard drugs, in some cases in half the time.
Vertex's telaprevir eliminated the hepatitis C virus in 79 percent of newly treated patients, FDA reviewers said. That was higher than the 75 percent Vertex reported earlier because the FDA used a different cure rate calculation.
Analysts said the higher effectiveness, plus few FDA safety concerns, meant an advisory panel would likely recommend approval of the drug on Thursday.
"We now expect telaprevir to get a relatively clean recommendation (and hence approval) with no significant exclusions, restrictions, warnings or caveats," Sanford Bernstein analyst Geoffrey Porges said in a research note.
Current therapies require almost a year of treatment and often cause flu-like symptoms that are tough to tolerate, with only about a 40 percent success rate. Both of the new medicines work by blocking a protein called protease that the virus needs to replicate.
WAITING FOR TREATMENT
Doctors say tens of thousands of patients have been delaying treatment in anticipation of the new anti-virals, which still must be taken in combination with the older drugs ribavirin and interferon.
Hepatitis C is a bloodborne liver disease that can lead to chronic liver problems, liver cancer, cirrhosis and death. It is spread mainly through reuse of needles such as those used for illegal drugs and tattoos, or through blood transfusions before 1992 when screening began. About 3.2 million Americans and 170 million people worldwide have the disease.
Analysts widely expect the Vertex pill to dominate the market with its greater effectiveness. Telaprevir's 79 percent success rate compares with up to 66 percent for Merck's drug, boceprevir, in previously untreated patients. It also had a higher cure rate than the Merck drug in patients who had failed to be helped by prior therapy.
"Overall, the FDA review team's independent analyses confirmed the applicant's primary efficacy findings," FDA staff said in a summary prepared for the advisory panel of outside experts.
The FDA reviewers said they would ask the panel to discuss rashes and anemia seen in clinical trials of telaprevir. Those issues were known and analysts do not expect them to derail the drug's approval.
An FDA panel will review the Merck drug on Wednesday. In documents released on Monday, agency reviewers said Merck's drug appeared effective but highlighted anemia and other safety issues for panel discussion.
The FDA usually approves medicines that win advisory panel backing. An approval decision for either drug could come as early as May.
(Additional reporting by Toni Clarke and Bill Berkrot, editing by Michele Gershberg, Gerald E. McCormick, Derek Caney and Bernard Orr)
Wednesday, April 27, 2011
FDA advisory board gives Boceprevir the green light, FDA final decision will be in mid-May...
FDA Panel Backs Experimental Merck Hepatitis Drug
WASHINGTON April 27, 2011 (AP)
Federal health experts are recommending approval for a highly anticipated drug from Merck to treat hepatitis C, based on studies showing it cures patients at a higher rate than drugs used for over 20 years.
A Food and Drug Administration panel of experts voted unanimously, 18-0, in favor of Merck's boceprevir tablet as an effective treatment for hepatitis C, which affects an estimated 3.2 million Americans.
The agency is not required to follow the group's recommendation, though it usually does. A final decision is expected mid-May.
On Thursday the panel will review a similar drug from Vertex Pharmaceuticals. Both of the new drugs block the enzyme that helps the hepatitis virus reproduce.
Panelists said the drug is largely safe, but noted side effects including anemia and lower blood cell counts.
WASHINGTON April 27, 2011 (AP)
Federal health experts are recommending approval for a highly anticipated drug from Merck to treat hepatitis C, based on studies showing it cures patients at a higher rate than drugs used for over 20 years.
A Food and Drug Administration panel of experts voted unanimously, 18-0, in favor of Merck's boceprevir tablet as an effective treatment for hepatitis C, which affects an estimated 3.2 million Americans.
The agency is not required to follow the group's recommendation, though it usually does. A final decision is expected mid-May.
On Thursday the panel will review a similar drug from Vertex Pharmaceuticals. Both of the new drugs block the enzyme that helps the hepatitis virus reproduce.
Panelists said the drug is largely safe, but noted side effects including anemia and lower blood cell counts.
Tuesday, April 26, 2011
New drug targets raise hopes for hepatitis C cure
Article appearing in the online "news" section of the journal Nature, discussing how the best in HCV treatment - and prevention of resistance - may be yet to come with drugs currently in the development pipeline. Companies mentioned are Pharmasset, BMS and iTherX.
New drug targets raise hopes for hepatitis C cure
As the first targeted therapies edge towards regulatory approval, attention turns to the next drugs in line.
Heidi Ledford
A cocktail of tailored drugs will be needed to defeat the hepatitis C virus.
This week, a panel of advisers to the US Food and Drug Administration (FDA) will decide whether the regulator should approve the first therapies tailored to target the hepatitis C virus (HCV). The drugs, called protease inhibitors, are expected to win approval, but observers say that they are only the beginning of a revolution in HCV treatment.
The most exciting developments for patients, they say, may still be in the drug-development pipeline. Researchers are working on drugs that target many aspects of the virus's biology. Used in combination, these might thwart HCV's ability to evolve resistance.
About 3% of the world's population is infected with HCV, an RNA virus that can cause chronic liver disease. Current therapy — a year-long regimen of the antiviral compounds interferon-alpha and ribavirin — cures only about half of cases. Side effects of this treatment can be severe: interferon-alpha can cause flu-like symptoms, fatigue, anaemia and depression.
On 27 and 28 April, the FDA's Antiviral Drugs Advisory Committee will meet to discuss the first anti-HCV drugs to target HCV proteins. Both these drugs — boceprevir, made by pharmaceutical giant Merck, headquartered in Whitehouse Station, New Jersey, and telaprevir from Vertex Pharmaceuticals, based in Cambridge, Massachusetts — target a protein called the NS3-4A protease, which is required to make essential viral proteins.
Each drug, when combined with standard therapy, boosts the cure rate to about 75%.
"I am very excited," says Michael Houghton, a virologist at the University of Alberta in Edmonton, who was a member of the team that discovered the virus in 1989. "These drugs are great news for HCV patients."
The long road to a blockbuster
Nevertheless, these drugs are only the beginning. "These first-generation protease inhibitors will enjoy their day in the sun for maybe two or three years," says Raymond Chung, head of hepatology at the Massachusetts General Hospital in Boston. "But I don't see them having staying power once we have many more of these targeted drugs getting into the game."
The hope is to eventually use several drugs in combination, avoiding the need for interferon-alpha while staving off drug resistance. Houghton estimates, based on mathematical models and clinical studies, that it will take a cocktail of three targeted therapies to prevent drug resistance.
There are about 60 compounds in preclinical and clinical development as companies jostle to grab a slice of a multi-billion-dollar market.
In 2010, researchers at Bristol-Myers-Squibb's lab in Wallingford, Connecticut, reported their discovery of an HCV protein called NS5A that is essential for the assembly of infectious viral particles and the amplification of viral RNA1. In early clinical trials of an NS5A inhibitor, the level of HCV RNA in the blood dropped almost 2,000-fold after only one day of treatment. This drug is now in phase 2 clinical trials.
Combining the NS5A inhibitor with a protease inhibitor wiped out the virus in four of 11 patients whose infections had not responded to standard therapy. The virus remained undetectable for at least 24 weeks.
These latest results, presented at the International Liver Congress annual meeting in Berlin on 1 April, are exciting because they suggest that interferon may eventually be dispensable, says Chung. He anticipates a flurry of such combination studies in the next few years.
Access denied
Another approach is to stop HCV spreading inside patients by targeting its ability to enter cells. "To contain the virus in a subset of cells rather than allowing it to spread would be a huge boost for containing liver damage," says Michael Gale, a virologist at the University of Washington in Seattle.
In a study published in Nature Medicine on 24 April, a team led by virologist Thomas Baumert of the University of Strasbourg, France, reports that HCV relies on a cellular receptor protein, the epidermal growth factor receptor (EGFR), to enter human cells2. EGFR inhibitors are already on the market as cancer therapies and Baumert's team plans to begin clinical trials of the EGFR inhibitor erlotinib in HCV patients by the end of the year.
Another drug that blocks entry, ITX-5061, is being developed by iTherX, a pharmaceutical company based in San Diego, California, and is in phase 2 clinical trials.
Chung, meanwhile, believes that drugs called nucleoside polymerase inhibitors, which prevent the virus from copying its genome, will be a key ingredient of any future HCV drug cocktail. These compounds set a high barrier for the virus, he notes, and early tests suggest that resistance to them is rare.
Pharmasset, a pharmaceutical firm in Princeton, New Jersey, has several such drugs in development. One called RG7128 is in phase 2 clinical trials and is being developed by Pharmasset together with the Swiss drug giant Roche, based in Basel.
"We used to live in a monochromatic world," says Chung. "Now we realize there are several roads to the same destination."
References
1.Gao, M. et al. Nature 465, 96-100 (2010).
2.Lupberger, J. et al. Nature Med. doi:10.1038/nm.2341 (2011).
New drug targets raise hopes for hepatitis C cure
As the first targeted therapies edge towards regulatory approval, attention turns to the next drugs in line.
Heidi Ledford
A cocktail of tailored drugs will be needed to defeat the hepatitis C virus.
This week, a panel of advisers to the US Food and Drug Administration (FDA) will decide whether the regulator should approve the first therapies tailored to target the hepatitis C virus (HCV). The drugs, called protease inhibitors, are expected to win approval, but observers say that they are only the beginning of a revolution in HCV treatment.
The most exciting developments for patients, they say, may still be in the drug-development pipeline. Researchers are working on drugs that target many aspects of the virus's biology. Used in combination, these might thwart HCV's ability to evolve resistance.
About 3% of the world's population is infected with HCV, an RNA virus that can cause chronic liver disease. Current therapy — a year-long regimen of the antiviral compounds interferon-alpha and ribavirin — cures only about half of cases. Side effects of this treatment can be severe: interferon-alpha can cause flu-like symptoms, fatigue, anaemia and depression.
On 27 and 28 April, the FDA's Antiviral Drugs Advisory Committee will meet to discuss the first anti-HCV drugs to target HCV proteins. Both these drugs — boceprevir, made by pharmaceutical giant Merck, headquartered in Whitehouse Station, New Jersey, and telaprevir from Vertex Pharmaceuticals, based in Cambridge, Massachusetts — target a protein called the NS3-4A protease, which is required to make essential viral proteins.
Each drug, when combined with standard therapy, boosts the cure rate to about 75%.
"I am very excited," says Michael Houghton, a virologist at the University of Alberta in Edmonton, who was a member of the team that discovered the virus in 1989. "These drugs are great news for HCV patients."
The long road to a blockbuster
Nevertheless, these drugs are only the beginning. "These first-generation protease inhibitors will enjoy their day in the sun for maybe two or three years," says Raymond Chung, head of hepatology at the Massachusetts General Hospital in Boston. "But I don't see them having staying power once we have many more of these targeted drugs getting into the game."
The hope is to eventually use several drugs in combination, avoiding the need for interferon-alpha while staving off drug resistance. Houghton estimates, based on mathematical models and clinical studies, that it will take a cocktail of three targeted therapies to prevent drug resistance.
There are about 60 compounds in preclinical and clinical development as companies jostle to grab a slice of a multi-billion-dollar market.
In 2010, researchers at Bristol-Myers-Squibb's lab in Wallingford, Connecticut, reported their discovery of an HCV protein called NS5A that is essential for the assembly of infectious viral particles and the amplification of viral RNA1. In early clinical trials of an NS5A inhibitor, the level of HCV RNA in the blood dropped almost 2,000-fold after only one day of treatment. This drug is now in phase 2 clinical trials.
Combining the NS5A inhibitor with a protease inhibitor wiped out the virus in four of 11 patients whose infections had not responded to standard therapy. The virus remained undetectable for at least 24 weeks.
These latest results, presented at the International Liver Congress annual meeting in Berlin on 1 April, are exciting because they suggest that interferon may eventually be dispensable, says Chung. He anticipates a flurry of such combination studies in the next few years.
Access denied
Another approach is to stop HCV spreading inside patients by targeting its ability to enter cells. "To contain the virus in a subset of cells rather than allowing it to spread would be a huge boost for containing liver damage," says Michael Gale, a virologist at the University of Washington in Seattle.
In a study published in Nature Medicine on 24 April, a team led by virologist Thomas Baumert of the University of Strasbourg, France, reports that HCV relies on a cellular receptor protein, the epidermal growth factor receptor (EGFR), to enter human cells2. EGFR inhibitors are already on the market as cancer therapies and Baumert's team plans to begin clinical trials of the EGFR inhibitor erlotinib in HCV patients by the end of the year.
Another drug that blocks entry, ITX-5061, is being developed by iTherX, a pharmaceutical company based in San Diego, California, and is in phase 2 clinical trials.
Chung, meanwhile, believes that drugs called nucleoside polymerase inhibitors, which prevent the virus from copying its genome, will be a key ingredient of any future HCV drug cocktail. These compounds set a high barrier for the virus, he notes, and early tests suggest that resistance to them is rare.
Pharmasset, a pharmaceutical firm in Princeton, New Jersey, has several such drugs in development. One called RG7128 is in phase 2 clinical trials and is being developed by Pharmasset together with the Swiss drug giant Roche, based in Basel.
"We used to live in a monochromatic world," says Chung. "Now we realize there are several roads to the same destination."
References
1.Gao, M. et al. Nature 465, 96-100 (2010).
2.Lupberger, J. et al. Nature Med. doi:10.1038/nm.2341 (2011).
Boehringer Ingelheim enrolls first patient in Phase 3 trial for BI 201335
Good news for BI as the first patient is enrolled in their phase 3 trials looking at HCV protease inhibitior BI 201335 in combinations with peg and riba. VERY nice to see that they will be looking at this compound in the HIV/HCV co-infected patient, an area that the first generation of protease inhibitors, Telaprevir and Boceprevir may be lacking in due to drug interaction and tolerability issues
Boehringer Ingelheim Announces Enrollment of First Patient in Phase 3 Trial for Lead Hepatitis C Compound
Development program has been granted FDA Fast Track designation
RIDGEFIELD, Conn., April 26, 2011 /PRNewswire/ -- Boehringer Ingelheim Pharmaceuticals, Inc. today announced that enrollment has commenced at North American sites in its pivotal Phase 3 clinical trial program for BI 201335, the Company's investigational, oral protease inhibitor for the treatment of chronic hepatitis C virus (HCV). Phase 3 trials have begun recruiting to evaluate BI 201335 plus standard-of-care (SOC) in both treatment-naive and -experienced patients with chronic genotype-1 HCV, the most challenging HCV genotype to treat.(1) Results from the Phase 3 studies are expected in the first half of 2013.
The U.S. Food and Drug Administration (FDA) has granted Fast Track designation for the development program for BI 201335. Fast Track is a process designed to facilitate the development and expedite the review of drugs to treat serious diseases and fill an unmet medical need. The purpose is to get important new drugs to patients earlier.(2)
"We are pleased to have begun enrolling patients at North American trial sites as we continue development of BI 201335," said Peter Piliero, M.D., executive director, Medical Affairs, Boehringer Ingelheim Pharmaceuticals, Inc. "We look forward to initiating additional trials later this year in more patient populations, including HCV-HIV coinfected patients, as we continue to advance our HCV portfolio."
BI 201335 U.S. Phase 3 Trials
There are currently three Phase 3 trials enrolling patients around the world that together seek to enroll approximately 1,875 patients. Two of the three trials have U.S. trial sites that together plan to enroll approximately 495 patients.
In the U.S., Study 1220.47 will enroll approximately 370 treatment-naive genotype-1 HCV patients at 95 trial sites. This study will also include additional sites in Canada, Taiwan and Korea. Study 1220.7 will enroll approximately 125 treatment-experienced genotype-1 HCV patients who have failed at least 12 weeks of prior treatment with SOC at 40 trial sites in the U.S. This study also includes additional trial sites around the world. In treatment-naive patients (Study 1220.47), BI 201335 will be dosed once-daily at either 120 mg or 240 mg for 12 or 24 weeks in combination with 24 or 48 weeks of pegylated interferon and ribavirin, the current HCV SOC. In treatment-experienced patients (Study 1220.7) BI 201335 will be dosed once-daily at 240 mg for 12 or 24 weeks in combination with SOC for 48 weeks for prior partial and null responder patients. Patients with prior relapse will be dosed with BI 201335 once-daily at 240 mg for 12 or 24 weeks in combination with SOC for 24 or 48 weeks total duration. The primary endpoint of each trial is sustained viral response (SVR), which is considered viral cure.(3)
For more information about clinical trials involving BI 201335, please visit www.clinicaltrials.gov.
About Hepatitis C Virus (HCV)
HCV is an infectious disease of the liver and is a leading cause of chronic liver disease and liver transplant.(1,4) The number of individuals chronically infected with HCV globally has been estimated at 170 million, with three to four million new infections occurring each year.(5) Only about 20-45 percent of patients clear the virus in the acute phase.(5) Of the remaining chronically infected patients, 20 percent will develop cirrhosis within a mean of 20 years.(1) The mortality rate after cirrhosis has developed is two to five percent per year.(6) End-stage liver disease due to HCV infection currently represents the major cause for liver transplantation in the Western world.(1)
About Boehringer Ingelheim in Virology
Boehringer Ingelheim has more than 6,900 scientists working in cross disciplinary teams within our global R&D network in six large therapeutic areas, including virology. In addition to its ongoing research program for HCV, Boehringer Ingelheim has a long-standing history in virology drug development, including compounds for the treatment of HIV. The company has a well established research center in Laval, Canada, dedicated to virology research since the early 1990's, and is committed to developing new therapies for virologic diseases with a high unmet medical need.
Boehringer Ingelheim in Hepatitis C Virus (HCV)
BI 201335 is an investigational oral HCV NS3/4A protease inhibitor, discovered from Boehringer Ingelheim's own research and development, which has completed clinical trials through Phase 2b (SILEN-C studies). This Phase 2 program supports the investigation of BI 201335 in Phase 3 trials. Boehringer Ingelheim is also developing BI 207127, an NS5B RNA-dependent polymerase inhibitor that has completed Phase 1 clinical trials. Phase 2 trials evaluating BI 207127 with BI 201335 in interferon-sparing regimens, both with and without ribavirin, are currently underway.
About Boehringer Ingelheim Pharmaceuticals, Inc.
Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies.
The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 145 affiliates and more than 42,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.
As a central element of its culture, Boehringer Ingelheim pledges to act socially responsible. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees form the foundation of the global operations. Mutual cooperation and respect, as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheim's endeavors.
For more information, please visit http://us.boehringer-ingelheim.com and follow us on Twitter at http://twitter.com/boehringerus.
References:
National Digestive Disease Information Clearing House (NDDICH), NIH. Chronic Hepatitis C: Current Disease Management. http://digestive.niddk.nih.gov/ddiseases/pubs/chronichepc/index.htm.
U.S. Food and Drug Administration (FDA). Fast Track Designation Request Performance. http://www.fda.gov/AboutFDA/CentersOffices/CBER/ucm122932.htm.
American Association for the Study of Liver Disease Practice Guidelines: Diagnosis, Management, and Treatment of Hepatitis C: An Update. Hepatology, April 2009. http://www.natap.org/2009/HCV/aasld.pdf.
Centers for Disease Control and Prevention (CDC). Hepatitis C FAQs for the Public. http://www.cdc.gov/hepatitis/C/cFAQ.htm.
World Health Organization (WHO): Europe. Hepatitis: Hepatitis C. http://www.euro.who.int/en/what-we-do/health-topics/diseases-and-conditions/hepatitis/facts-and-figures/hepatitis-c.
Soriano, Vincent et al. New Therapies for Hepatitis C Virus Infection. Clinical Infectious Disease, February 2009. http://cid.oxfordjournals.org/content/48/3/313.full.
SOURCE Boehringer Ingelheim Pharmaceuticals, Inc.
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RELATED LINKS
http://us.boehringer-ingelheim.com
Boehringer Ingelheim Announces Enrollment of First Patient in Phase 3 Trial for Lead Hepatitis C Compound
Development program has been granted FDA Fast Track designation
RIDGEFIELD, Conn., April 26, 2011 /PRNewswire/ -- Boehringer Ingelheim Pharmaceuticals, Inc. today announced that enrollment has commenced at North American sites in its pivotal Phase 3 clinical trial program for BI 201335, the Company's investigational, oral protease inhibitor for the treatment of chronic hepatitis C virus (HCV). Phase 3 trials have begun recruiting to evaluate BI 201335 plus standard-of-care (SOC) in both treatment-naive and -experienced patients with chronic genotype-1 HCV, the most challenging HCV genotype to treat.(1) Results from the Phase 3 studies are expected in the first half of 2013.
The U.S. Food and Drug Administration (FDA) has granted Fast Track designation for the development program for BI 201335. Fast Track is a process designed to facilitate the development and expedite the review of drugs to treat serious diseases and fill an unmet medical need. The purpose is to get important new drugs to patients earlier.(2)
"We are pleased to have begun enrolling patients at North American trial sites as we continue development of BI 201335," said Peter Piliero, M.D., executive director, Medical Affairs, Boehringer Ingelheim Pharmaceuticals, Inc. "We look forward to initiating additional trials later this year in more patient populations, including HCV-HIV coinfected patients, as we continue to advance our HCV portfolio."
BI 201335 U.S. Phase 3 Trials
There are currently three Phase 3 trials enrolling patients around the world that together seek to enroll approximately 1,875 patients. Two of the three trials have U.S. trial sites that together plan to enroll approximately 495 patients.
In the U.S., Study 1220.47 will enroll approximately 370 treatment-naive genotype-1 HCV patients at 95 trial sites. This study will also include additional sites in Canada, Taiwan and Korea. Study 1220.7 will enroll approximately 125 treatment-experienced genotype-1 HCV patients who have failed at least 12 weeks of prior treatment with SOC at 40 trial sites in the U.S. This study also includes additional trial sites around the world. In treatment-naive patients (Study 1220.47), BI 201335 will be dosed once-daily at either 120 mg or 240 mg for 12 or 24 weeks in combination with 24 or 48 weeks of pegylated interferon and ribavirin, the current HCV SOC. In treatment-experienced patients (Study 1220.7) BI 201335 will be dosed once-daily at 240 mg for 12 or 24 weeks in combination with SOC for 48 weeks for prior partial and null responder patients. Patients with prior relapse will be dosed with BI 201335 once-daily at 240 mg for 12 or 24 weeks in combination with SOC for 24 or 48 weeks total duration. The primary endpoint of each trial is sustained viral response (SVR), which is considered viral cure.(3)
For more information about clinical trials involving BI 201335, please visit www.clinicaltrials.gov.
About Hepatitis C Virus (HCV)
HCV is an infectious disease of the liver and is a leading cause of chronic liver disease and liver transplant.(1,4) The number of individuals chronically infected with HCV globally has been estimated at 170 million, with three to four million new infections occurring each year.(5) Only about 20-45 percent of patients clear the virus in the acute phase.(5) Of the remaining chronically infected patients, 20 percent will develop cirrhosis within a mean of 20 years.(1) The mortality rate after cirrhosis has developed is two to five percent per year.(6) End-stage liver disease due to HCV infection currently represents the major cause for liver transplantation in the Western world.(1)
About Boehringer Ingelheim in Virology
Boehringer Ingelheim has more than 6,900 scientists working in cross disciplinary teams within our global R&D network in six large therapeutic areas, including virology. In addition to its ongoing research program for HCV, Boehringer Ingelheim has a long-standing history in virology drug development, including compounds for the treatment of HIV. The company has a well established research center in Laval, Canada, dedicated to virology research since the early 1990's, and is committed to developing new therapies for virologic diseases with a high unmet medical need.
Boehringer Ingelheim in Hepatitis C Virus (HCV)
BI 201335 is an investigational oral HCV NS3/4A protease inhibitor, discovered from Boehringer Ingelheim's own research and development, which has completed clinical trials through Phase 2b (SILEN-C studies). This Phase 2 program supports the investigation of BI 201335 in Phase 3 trials. Boehringer Ingelheim is also developing BI 207127, an NS5B RNA-dependent polymerase inhibitor that has completed Phase 1 clinical trials. Phase 2 trials evaluating BI 207127 with BI 201335 in interferon-sparing regimens, both with and without ribavirin, are currently underway.
About Boehringer Ingelheim Pharmaceuticals, Inc.
Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies.
The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 145 affiliates and more than 42,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.
As a central element of its culture, Boehringer Ingelheim pledges to act socially responsible. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees form the foundation of the global operations. Mutual cooperation and respect, as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheim's endeavors.
For more information, please visit http://us.boehringer-ingelheim.com and follow us on Twitter at http://twitter.com/boehringerus.
References:
National Digestive Disease Information Clearing House (NDDICH), NIH. Chronic Hepatitis C: Current Disease Management. http://digestive.niddk.nih.gov/ddiseases/pubs/chronichepc/index.htm.
U.S. Food and Drug Administration (FDA). Fast Track Designation Request Performance. http://www.fda.gov/AboutFDA/CentersOffices/CBER/ucm122932.htm.
American Association for the Study of Liver Disease Practice Guidelines: Diagnosis, Management, and Treatment of Hepatitis C: An Update. Hepatology, April 2009. http://www.natap.org/2009/HCV/aasld.pdf.
Centers for Disease Control and Prevention (CDC). Hepatitis C FAQs for the Public. http://www.cdc.gov/hepatitis/C/cFAQ.htm.
World Health Organization (WHO): Europe. Hepatitis: Hepatitis C. http://www.euro.who.int/en/what-we-do/health-topics/diseases-and-conditions/hepatitis/facts-and-figures/hepatitis-c.
Soriano, Vincent et al. New Therapies for Hepatitis C Virus Infection. Clinical Infectious Disease, February 2009. http://cid.oxfordjournals.org/content/48/3/313.full.
SOURCE Boehringer Ingelheim Pharmaceuticals, Inc.
Back to top
RELATED LINKS
http://us.boehringer-ingelheim.com
Monday, April 25, 2011
Boceprevir Wins Favorable FDA Staff Review
MedPage Today covers FDA review of Boceprevir. Aside from the issues regarding Merck's definition of 'null responder', the predictive value of viral kinetics and the hemotologic issues with the drug, the only formal voting issue, however, is whether "the available data support approval" of boceprevir for treating HCV genotype 1 in combination with peginterferon and ribavirin.
Boceprevir Wins Favorable FDA Staff Review
By John Gever, Senior Editor, MedPage Today
Published: April 25, 2011
WASHINGTON -- The FDA's professional staff believes the investigational hepatitis C drug boceprevir (Victrelis) is effective and reasonably safe, according to a briefing document made public in advance of a Wednesday advisory committee meeting.
But before the agency approves the drug, it wants the panel's views on certain marketing claims that the drug's manufacturer, Merck, is proposing to make. These include the drug's efficacy in patients with "null" responses to the standard regimen of pegylated interferon and ribavirin as well as the benefits of so-called response-guided therapy.
The Antiviral Drugs Advisory Committee will also be asked to review risks of anemia and other hematologic abnormalities associated with boceprevir.
The drug is one of two hepatitis C virus (HCV) protease inhibitors that will be reviewed during a two-day meeting this week. The other is telaprevir -- no brand name has been proposed as yet -- which will have its day on Thursday.
The two drugs would be the first HCV protease inhibitors to reach the market. They have attracted major buzz among physicians and patients on the basis of excellent-looking clinical trial results, most recently from two of boceprevir's pivotal studies published in the New England Journal of Medicine last month.
These data suggest that adding one of the drugs to the standard peginterferon-ribavirin combination doubles or triples the sustained viral response rates.
For example, among treatment-naive patients in one of the boceprevir trials, 40% of a control group receiving the conventional regimen had a sustained response versus about 70% of patients with the protease inhibitor added.
A separate trial in patients with previous partial or unsustained responses to the standard regimen showed that 21% achieved a sustained response with a second round, whereas approximately 60% did with the addition of boceprevir.
In the briefing paper prepared for Wednesday's panel meeting, the FDA staff reviewers could find little to fault in these data.
But they did question Merck's arguments in favor of "response-guided therapy," particularly in African-American patients and raised concerns about the drug's hematologic side effects.
The core treatment regimen with boceprevir tested in the trials included a four-week lead-in period with peginterferon and ribavirin with boceprevir then added for 44 weeks. But some of the trials also included a regimen in which the duration of boceprevir treatment could be extended based on viral responses after eight and 24 weeks.
In particular, Merck would like the drug's label to allow longer treatment for patients with detectable HCV RNA at eight weeks but who achieve a full virologic response at 24 weeks, as some data suggested that such a regimen improves the sustained response rate.
But the FDA staff reviewers pointed to data in one of the trials indicating a slightly lower sustained-response rate in previous treatment failures receiving the response-guided therapy compared with fixed-duration treatment (59% versus 66%).
They also noted that black participants in a study of treatment-naive patients also had a lower sustained-response rate with response-guided therapy (42% versus 53%).
"The 11% numerical difference ... is of some concern and will be an issue for discussion," the briefing paper said.
Another issue is whether a proposed indication for patients who completely failed previous peginterferon-ribavirin therapy is justified, considering that such patients were excluded from trials of previously treated patients.
Merck is arguing that its major trial in treatment-naive patients included null responders, identified as those with negligible responses during the lead-in with standard therapy, and the drug's efficacy in this population can be gauged from those results.
However, the FDA reviewers indicated that responses at week four do not perfectly predict who will ultimately respond. The lack of a trial designed expressly to test the drug in null responders "raises questions about using [standard therapy] lead-in responses as a surrogate," they wrote in the briefing document.
About a quarter of the briefing document was devoted to boceprevir's adverse hematologic effects, primarily anemia but also including neutropenia and thrombocytopenia.
In the drug's two main phase III trials, half the patients taking the drug had nadir hemoglobin values of 10 g/dL or below and more than 40% required erythropoietin therapy -- with both rates about twice those seen in the control groups.
The other hematologic effects were far less common, but still a potential concern, according the briefing document.
Counting all cases, the incidence of neutropenia was about the same with or without boceprevir, but the drug was associated with a greater rate of serious cases. Eight of 1,057 patients taking the drug discontinued the study because of neutropenia compared with none in the control groups.
Similarly, severe thrombocytopenia was seen in 15 boceprevir-treated patients compared with three control patients.
The FDA plans to ask the advisory panel to comment on these adverse events, as well as to discuss postmarketing studies that Merck should conduct if the product is approved.
The only formal voting issue, however, is whether "the available data support approval" of boceprevir for treating HCV genotype 1 in combination with peginterferon and ribavirin.
Boceprevir Wins Favorable FDA Staff Review
By John Gever, Senior Editor, MedPage Today
Published: April 25, 2011
WASHINGTON -- The FDA's professional staff believes the investigational hepatitis C drug boceprevir (Victrelis) is effective and reasonably safe, according to a briefing document made public in advance of a Wednesday advisory committee meeting.
But before the agency approves the drug, it wants the panel's views on certain marketing claims that the drug's manufacturer, Merck, is proposing to make. These include the drug's efficacy in patients with "null" responses to the standard regimen of pegylated interferon and ribavirin as well as the benefits of so-called response-guided therapy.
The Antiviral Drugs Advisory Committee will also be asked to review risks of anemia and other hematologic abnormalities associated with boceprevir.
The drug is one of two hepatitis C virus (HCV) protease inhibitors that will be reviewed during a two-day meeting this week. The other is telaprevir -- no brand name has been proposed as yet -- which will have its day on Thursday.
The two drugs would be the first HCV protease inhibitors to reach the market. They have attracted major buzz among physicians and patients on the basis of excellent-looking clinical trial results, most recently from two of boceprevir's pivotal studies published in the New England Journal of Medicine last month.
These data suggest that adding one of the drugs to the standard peginterferon-ribavirin combination doubles or triples the sustained viral response rates.
For example, among treatment-naive patients in one of the boceprevir trials, 40% of a control group receiving the conventional regimen had a sustained response versus about 70% of patients with the protease inhibitor added.
A separate trial in patients with previous partial or unsustained responses to the standard regimen showed that 21% achieved a sustained response with a second round, whereas approximately 60% did with the addition of boceprevir.
In the briefing paper prepared for Wednesday's panel meeting, the FDA staff reviewers could find little to fault in these data.
But they did question Merck's arguments in favor of "response-guided therapy," particularly in African-American patients and raised concerns about the drug's hematologic side effects.
The core treatment regimen with boceprevir tested in the trials included a four-week lead-in period with peginterferon and ribavirin with boceprevir then added for 44 weeks. But some of the trials also included a regimen in which the duration of boceprevir treatment could be extended based on viral responses after eight and 24 weeks.
In particular, Merck would like the drug's label to allow longer treatment for patients with detectable HCV RNA at eight weeks but who achieve a full virologic response at 24 weeks, as some data suggested that such a regimen improves the sustained response rate.
But the FDA staff reviewers pointed to data in one of the trials indicating a slightly lower sustained-response rate in previous treatment failures receiving the response-guided therapy compared with fixed-duration treatment (59% versus 66%).
They also noted that black participants in a study of treatment-naive patients also had a lower sustained-response rate with response-guided therapy (42% versus 53%).
"The 11% numerical difference ... is of some concern and will be an issue for discussion," the briefing paper said.
Another issue is whether a proposed indication for patients who completely failed previous peginterferon-ribavirin therapy is justified, considering that such patients were excluded from trials of previously treated patients.
Merck is arguing that its major trial in treatment-naive patients included null responders, identified as those with negligible responses during the lead-in with standard therapy, and the drug's efficacy in this population can be gauged from those results.
However, the FDA reviewers indicated that responses at week four do not perfectly predict who will ultimately respond. The lack of a trial designed expressly to test the drug in null responders "raises questions about using [standard therapy] lead-in responses as a surrogate," they wrote in the briefing document.
About a quarter of the briefing document was devoted to boceprevir's adverse hematologic effects, primarily anemia but also including neutropenia and thrombocytopenia.
In the drug's two main phase III trials, half the patients taking the drug had nadir hemoglobin values of 10 g/dL or below and more than 40% required erythropoietin therapy -- with both rates about twice those seen in the control groups.
The other hematologic effects were far less common, but still a potential concern, according the briefing document.
Counting all cases, the incidence of neutropenia was about the same with or without boceprevir, but the drug was associated with a greater rate of serious cases. Eight of 1,057 patients taking the drug discontinued the study because of neutropenia compared with none in the control groups.
Similarly, severe thrombocytopenia was seen in 15 boceprevir-treated patients compared with three control patients.
The FDA plans to ask the advisory panel to comment on these adverse events, as well as to discuss postmarketing studies that Merck should conduct if the product is approved.
The only formal voting issue, however, is whether "the available data support approval" of boceprevir for treating HCV genotype 1 in combination with peginterferon and ribavirin.
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