AASLD: Hepatologists Eye Protease Inhibitors for Hepatitis C

[Guest guest]

http://www.medpagetoday.com/MeetingCoverage/AASLD/11620

Medical News from

AASLD: American Association for the Study of Liver Diseases Meeting

AASLD: Hepatologists Eye Protease Inhibitors for Hepatitis C

By , North American Correspondent, MedPage Today

Published: November 04, 2008

Reviewed by Jasmer, MD; Associate Clinical Professor of Medicine,

University of California, San Francisco Earn CME/CE credit

for reading medical news

SAN FRANCISCO, Nov. 4 -- Drugs that inhibit the protease enzyme of hepatitis C

attracted considerable interest at the American Association for the Study of

Liver Diseases meeting here.

Several protease inhibitors are in the pipeline, but the two closest to market

are boceprevir and telaprevir. On the basis of phase II data, both were the

subject of several presentations here.

So far, both drugs appear to be effective with acceptable side effect profiles,

according to Arthur McCullough, M.D., of the Cleveland Clinic, who is president

of the liver association and was not involved in the studies.

He added that the new drugs offer the chance to improve on standard therapy for

chronic HCV. " If we are only getting a 45% (sustained virological response), we

need to do something else, " Dr. McCullough said. Action Points

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

Explain to interested patients that protease inhibitors -- well-known in the

treatment of HIV -- are under investigation for the treatment of hepatitis C.

Note that these studies report progress in studies of the two most advanced

drugs under study.

Note that these studies were published as abstracts and presented orally or in

poster form at a conference. These data and conclusions should be considered to

be preliminary until published in a peer-reviewed journal.

One experiment reported with boceprevir almost doubled sustained virological

response, which would be " a significant advance " if it holds up in phase III

clinical trials, he said.

That investigation involved a four-week lead-in with pegylated interferon and

ribavirin -- the standard of care for HCV -- before adding boceprevir for

another 44 weeks, said Kwo, M.D., of Indiana University in Indianapolis.

Dr. Kwo, the principal investigator of the so-called SPRINT-1 study, said that

after the 48 weeks of treatment, the sustained virological response (measured

after 12 weeks of follow-up) was 74%.

In contrast, the sustained virological response in the control arm -- just

interferon and ribavirin -- was 38%.

" That's tremendous, that's a delta, " he said, using the mathematical term for a

change.

The study randomized 595 patients to one of five arms:

Standard therapy with interferon and ribavirin, whose volunteers acted as

controls

A 28-week arm with all three drugs

A 28-week arm, starting with a four-week interferon/ribavirin lead-in, followed

by all three drugs for 24 weeks

A 48-week arm with all three drugs

And a 48-week arm starting with a four-week interferon/ribavirin lead-in,

followed by all three drugs for 44 weeks

The last arm has the investigators most excited, but all of the investigational

arms outperformed controls, although Dr. Kwo said the researchers will have to

wait for further analysis to see if the differences are statistically

significant.

It also seems clear, he said, the some patients will do well on the shorter arms

and " the challenge " will be to figure who will need the longer therapeutic

period.

It is also still not clear which patients will do better with the lead-in, he

said.

The two main adverse events that were linked to the drug were dysgeusia -- a bad

taste in the mouth -- and about a 0.5 to 1.0 gram per deciliter reduction in

hemoglobin levels in addition to the anemia caused by ribavirin.

" That's (the anemia) not concerning, but it's real, " he said.

Investigators looking at the other drug, telaprevir, are focusing on shorter

therapeutic durations, according to Stefan Zeuzem, M.D., of J.W. Goethe

University Hospital in furt, Germany.

Dr. Zeuzem reported that the final results of the so-called PROVE2 study,

conducted in Europe, show that the time for first undetectable level of

hepatitis RNA is markedly shortened by the addition of telaprevir to standard

medications.

Like the boceprevir trial, the PROVE2 study had several arms:

A control arm, in which 82 patients got a placebo plus pegylated interferon and

ribavirin for 12 weeks, followed by 36 weeks of interferon and ribivarin alone

An arm in which 78 patients got telaprevir and interferon alone for 12 weeks

An arm in which 82 patients got telaprevir plus interferon and ribavirin for 12

weeks

And an arm in which 81 patients got telaprevir plus interferon and ribavirin for

12 weeks, followed by interferon and ribavirin for another 12 weeks

The key efficacy result was that the two arms containing both telaprevir and

ribavirin did better at most time points than the control arm, Dr. Zeuzem said.

" The addition of ribavirin leads to better efficacy, " he said.

The sustained virological response of the two telaprevir/ribavirin arms was 60%

and 69%, respectively, compared with 46% for the control arm, Dr. Zeuzem

reported.

The difference was significant (at P=0.004) for the 24-week arm, but fell short

of significance for the 12-week arm, he said, although improvements in response

were significant at earlier times in the study.

The most common adverse events leading to stopping the trial were rash and

pruritis, all in the experimental arms, Dr. Zeuzem said. All told, 12 patients,

or 7%, discontinued all study drugs due to rash, which was typically

maculopapular exanthema.

Late-stage clinical trials for both drugs are under way.

The boceprevir study was sponsored by Schering-Plough. Dr. Kwo reported

financial links to Indenix, Human Genome Sciences, Merck, Novartis,

Schering-Plough, and Vertex.

The telaprevir study was sponsored by Vertex Pharmaceuticals. Dr. Zeuzem

reported financial links with Tibotec, Vertex, and Roche.

Primary source: Hepatology

Source reference:

Kwo P, et al " HCV SPRINT-1: Boceprevir plus Peginterferon alfa-2b/Ribavirin for

Treatment of Genotype 1 Chronic Hepatitis C in Previously Untreated Patients "

Hepatology 2008; 48(4): Abstract LB16.

Additional source: Hepatology

Source reference:

Zeuzem S, et al " Telaprevir in Combination with Peginterferon-Alfa-2a with or

without Ribavirin in the Treatment of Chronic Hepatitis C: Final Results of the

PROVE2 Study " Hepatology 2008; 48(4): Abstract 243

[Guest guest]

http://www.medpagetoday.com/MeetingCoverage/AASLD/11620

Medical News from

AASLD: American Association for the Study of Liver Diseases Meeting

AASLD: Hepatologists Eye Protease Inhibitors for Hepatitis C

By , North American Correspondent, MedPage Today

Published: November 04, 2008

Reviewed by Jasmer, MD; Associate Clinical Professor of Medicine,

University of California, San Francisco Earn CME/CE credit

for reading medical news

SAN FRANCISCO, Nov. 4 -- Drugs that inhibit the protease enzyme of hepatitis C

attracted considerable interest at the American Association for the Study of

Liver Diseases meeting here.

Several protease inhibitors are in the pipeline, but the two closest to market

are boceprevir and telaprevir. On the basis of phase II data, both were the

subject of several presentations here.

So far, both drugs appear to be effective with acceptable side effect profiles,

according to Arthur McCullough, M.D., of the Cleveland Clinic, who is president

of the liver association and was not involved in the studies.

He added that the new drugs offer the chance to improve on standard therapy for

chronic HCV. " If we are only getting a 45% (sustained virological response), we

need to do something else, " Dr. McCullough said. Action Points

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

Explain to interested patients that protease inhibitors -- well-known in the

treatment of HIV -- are under investigation for the treatment of hepatitis C.

Note that these studies report progress in studies of the two most advanced

drugs under study.

Note that these studies were published as abstracts and presented orally or in

poster form at a conference. These data and conclusions should be considered to

be preliminary until published in a peer-reviewed journal.

One experiment reported with boceprevir almost doubled sustained virological

response, which would be " a significant advance " if it holds up in phase III

clinical trials, he said.

That investigation involved a four-week lead-in with pegylated interferon and

ribavirin -- the standard of care for HCV -- before adding boceprevir for

another 44 weeks, said Kwo, M.D., of Indiana University in Indianapolis.

Dr. Kwo, the principal investigator of the so-called SPRINT-1 study, said that

after the 48 weeks of treatment, the sustained virological response (measured

after 12 weeks of follow-up) was 74%.

In contrast, the sustained virological response in the control arm -- just

interferon and ribavirin -- was 38%.

" That's tremendous, that's a delta, " he said, using the mathematical term for a

change.

The study randomized 595 patients to one of five arms:

Standard therapy with interferon and ribavirin, whose volunteers acted as

controls

A 28-week arm with all three drugs

A 28-week arm, starting with a four-week interferon/ribavirin lead-in, followed

by all three drugs for 24 weeks

A 48-week arm with all three drugs

And a 48-week arm starting with a four-week interferon/ribavirin lead-in,

followed by all three drugs for 44 weeks

The last arm has the investigators most excited, but all of the investigational

arms outperformed controls, although Dr. Kwo said the researchers will have to

wait for further analysis to see if the differences are statistically

significant.

It also seems clear, he said, the some patients will do well on the shorter arms

and " the challenge " will be to figure who will need the longer therapeutic

period.

It is also still not clear which patients will do better with the lead-in, he

said.

The two main adverse events that were linked to the drug were dysgeusia -- a bad

taste in the mouth -- and about a 0.5 to 1.0 gram per deciliter reduction in

hemoglobin levels in addition to the anemia caused by ribavirin.

" That's (the anemia) not concerning, but it's real, " he said.

Investigators looking at the other drug, telaprevir, are focusing on shorter

therapeutic durations, according to Stefan Zeuzem, M.D., of J.W. Goethe

University Hospital in furt, Germany.

Dr. Zeuzem reported that the final results of the so-called PROVE2 study,

conducted in Europe, show that the time for first undetectable level of

hepatitis RNA is markedly shortened by the addition of telaprevir to standard

medications.

Like the boceprevir trial, the PROVE2 study had several arms:

A control arm, in which 82 patients got a placebo plus pegylated interferon and

ribavirin for 12 weeks, followed by 36 weeks of interferon and ribivarin alone

An arm in which 78 patients got telaprevir and interferon alone for 12 weeks

An arm in which 82 patients got telaprevir plus interferon and ribavirin for 12

weeks

And an arm in which 81 patients got telaprevir plus interferon and ribavirin for

12 weeks, followed by interferon and ribavirin for another 12 weeks

The key efficacy result was that the two arms containing both telaprevir and

ribavirin did better at most time points than the control arm, Dr. Zeuzem said.

" The addition of ribavirin leads to better efficacy, " he said.

The sustained virological response of the two telaprevir/ribavirin arms was 60%

and 69%, respectively, compared with 46% for the control arm, Dr. Zeuzem

reported.

The difference was significant (at P=0.004) for the 24-week arm, but fell short

of significance for the 12-week arm, he said, although improvements in response

were significant at earlier times in the study.

The most common adverse events leading to stopping the trial were rash and

pruritis, all in the experimental arms, Dr. Zeuzem said. All told, 12 patients,

or 7%, discontinued all study drugs due to rash, which was typically

maculopapular exanthema.

Late-stage clinical trials for both drugs are under way.

The boceprevir study was sponsored by Schering-Plough. Dr. Kwo reported

financial links to Indenix, Human Genome Sciences, Merck, Novartis,

Schering-Plough, and Vertex.

The telaprevir study was sponsored by Vertex Pharmaceuticals. Dr. Zeuzem

reported financial links with Tibotec, Vertex, and Roche.

Primary source: Hepatology

Source reference:

Kwo P, et al " HCV SPRINT-1: Boceprevir plus Peginterferon alfa-2b/Ribavirin for

Treatment of Genotype 1 Chronic Hepatitis C in Previously Untreated Patients "

Hepatology 2008; 48(4): Abstract LB16.

Additional source: Hepatology

Source reference:

Zeuzem S, et al " Telaprevir in Combination with Peginterferon-Alfa-2a with or

without Ribavirin in the Treatment of Chronic Hepatitis C: Final Results of the

PROVE2 Study " Hepatology 2008; 48(4): Abstract 243

[Guest guest]

http://www.medpagetoday.com/MeetingCoverage/AASLD/11620

Medical News from

AASLD: American Association for the Study of Liver Diseases Meeting

AASLD: Hepatologists Eye Protease Inhibitors for Hepatitis C

By , North American Correspondent, MedPage Today

Published: November 04, 2008

Reviewed by Jasmer, MD; Associate Clinical Professor of Medicine,

University of California, San Francisco Earn CME/CE credit

for reading medical news

SAN FRANCISCO, Nov. 4 -- Drugs that inhibit the protease enzyme of hepatitis C

attracted considerable interest at the American Association for the Study of

Liver Diseases meeting here.

Several protease inhibitors are in the pipeline, but the two closest to market

are boceprevir and telaprevir. On the basis of phase II data, both were the

subject of several presentations here.

So far, both drugs appear to be effective with acceptable side effect profiles,

according to Arthur McCullough, M.D., of the Cleveland Clinic, who is president

of the liver association and was not involved in the studies.

He added that the new drugs offer the chance to improve on standard therapy for

chronic HCV. " If we are only getting a 45% (sustained virological response), we

need to do something else, " Dr. McCullough said. Action Points

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

Explain to interested patients that protease inhibitors -- well-known in the

treatment of HIV -- are under investigation for the treatment of hepatitis C.

Note that these studies report progress in studies of the two most advanced

drugs under study.

Note that these studies were published as abstracts and presented orally or in

poster form at a conference. These data and conclusions should be considered to

be preliminary until published in a peer-reviewed journal.

One experiment reported with boceprevir almost doubled sustained virological

response, which would be " a significant advance " if it holds up in phase III

clinical trials, he said.

That investigation involved a four-week lead-in with pegylated interferon and

ribavirin -- the standard of care for HCV -- before adding boceprevir for

another 44 weeks, said Kwo, M.D., of Indiana University in Indianapolis.

Dr. Kwo, the principal investigator of the so-called SPRINT-1 study, said that

after the 48 weeks of treatment, the sustained virological response (measured

after 12 weeks of follow-up) was 74%.

In contrast, the sustained virological response in the control arm -- just

interferon and ribavirin -- was 38%.

" That's tremendous, that's a delta, " he said, using the mathematical term for a

change.

The study randomized 595 patients to one of five arms:

Standard therapy with interferon and ribavirin, whose volunteers acted as

controls

A 28-week arm with all three drugs

A 28-week arm, starting with a four-week interferon/ribavirin lead-in, followed

by all three drugs for 24 weeks

A 48-week arm with all three drugs

And a 48-week arm starting with a four-week interferon/ribavirin lead-in,

followed by all three drugs for 44 weeks

The last arm has the investigators most excited, but all of the investigational

arms outperformed controls, although Dr. Kwo said the researchers will have to

wait for further analysis to see if the differences are statistically

significant.

It also seems clear, he said, the some patients will do well on the shorter arms

and " the challenge " will be to figure who will need the longer therapeutic

period.

It is also still not clear which patients will do better with the lead-in, he

said.

The two main adverse events that were linked to the drug were dysgeusia -- a bad

taste in the mouth -- and about a 0.5 to 1.0 gram per deciliter reduction in

hemoglobin levels in addition to the anemia caused by ribavirin.

" That's (the anemia) not concerning, but it's real, " he said.

Investigators looking at the other drug, telaprevir, are focusing on shorter

therapeutic durations, according to Stefan Zeuzem, M.D., of J.W. Goethe

University Hospital in furt, Germany.

Dr. Zeuzem reported that the final results of the so-called PROVE2 study,

conducted in Europe, show that the time for first undetectable level of

hepatitis RNA is markedly shortened by the addition of telaprevir to standard

medications.

Like the boceprevir trial, the PROVE2 study had several arms:

A control arm, in which 82 patients got a placebo plus pegylated interferon and

ribavirin for 12 weeks, followed by 36 weeks of interferon and ribivarin alone

An arm in which 78 patients got telaprevir and interferon alone for 12 weeks

An arm in which 82 patients got telaprevir plus interferon and ribavirin for 12

weeks

And an arm in which 81 patients got telaprevir plus interferon and ribavirin for

12 weeks, followed by interferon and ribavirin for another 12 weeks

The key efficacy result was that the two arms containing both telaprevir and

ribavirin did better at most time points than the control arm, Dr. Zeuzem said.

" The addition of ribavirin leads to better efficacy, " he said.

The sustained virological response of the two telaprevir/ribavirin arms was 60%

and 69%, respectively, compared with 46% for the control arm, Dr. Zeuzem

reported.

The difference was significant (at P=0.004) for the 24-week arm, but fell short

of significance for the 12-week arm, he said, although improvements in response

were significant at earlier times in the study.

The most common adverse events leading to stopping the trial were rash and

pruritis, all in the experimental arms, Dr. Zeuzem said. All told, 12 patients,

or 7%, discontinued all study drugs due to rash, which was typically

maculopapular exanthema.

Late-stage clinical trials for both drugs are under way.

The boceprevir study was sponsored by Schering-Plough. Dr. Kwo reported

financial links to Indenix, Human Genome Sciences, Merck, Novartis,

Schering-Plough, and Vertex.

The telaprevir study was sponsored by Vertex Pharmaceuticals. Dr. Zeuzem

reported financial links with Tibotec, Vertex, and Roche.

Primary source: Hepatology

Source reference:

Kwo P, et al " HCV SPRINT-1: Boceprevir plus Peginterferon alfa-2b/Ribavirin for

Treatment of Genotype 1 Chronic Hepatitis C in Previously Untreated Patients "

Hepatology 2008; 48(4): Abstract LB16.

Additional source: Hepatology

Source reference:

Zeuzem S, et al " Telaprevir in Combination with Peginterferon-Alfa-2a with or

without Ribavirin in the Treatment of Chronic Hepatitis C: Final Results of the

PROVE2 Study " Hepatology 2008; 48(4): Abstract 243

[Guest guest]

http://www.medpagetoday.com/MeetingCoverage/AASLD/11620

Medical News from

AASLD: American Association for the Study of Liver Diseases Meeting

AASLD: Hepatologists Eye Protease Inhibitors for Hepatitis C

By , North American Correspondent, MedPage Today

Published: November 04, 2008

Reviewed by Jasmer, MD; Associate Clinical Professor of Medicine,

University of California, San Francisco Earn CME/CE credit

for reading medical news

SAN FRANCISCO, Nov. 4 -- Drugs that inhibit the protease enzyme of hepatitis C

attracted considerable interest at the American Association for the Study of

Liver Diseases meeting here.

Several protease inhibitors are in the pipeline, but the two closest to market

are boceprevir and telaprevir. On the basis of phase II data, both were the

subject of several presentations here.

So far, both drugs appear to be effective with acceptable side effect profiles,

according to Arthur McCullough, M.D., of the Cleveland Clinic, who is president

of the liver association and was not involved in the studies.

He added that the new drugs offer the chance to improve on standard therapy for

chronic HCV. " If we are only getting a 45% (sustained virological response), we

need to do something else, " Dr. McCullough said. Action Points

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

Explain to interested patients that protease inhibitors -- well-known in the

treatment of HIV -- are under investigation for the treatment of hepatitis C.

Note that these studies report progress in studies of the two most advanced

drugs under study.

Note that these studies were published as abstracts and presented orally or in

poster form at a conference. These data and conclusions should be considered to

be preliminary until published in a peer-reviewed journal.

One experiment reported with boceprevir almost doubled sustained virological

response, which would be " a significant advance " if it holds up in phase III

clinical trials, he said.

That investigation involved a four-week lead-in with pegylated interferon and

ribavirin -- the standard of care for HCV -- before adding boceprevir for

another 44 weeks, said Kwo, M.D., of Indiana University in Indianapolis.

Dr. Kwo, the principal investigator of the so-called SPRINT-1 study, said that

after the 48 weeks of treatment, the sustained virological response (measured

after 12 weeks of follow-up) was 74%.

In contrast, the sustained virological response in the control arm -- just

interferon and ribavirin -- was 38%.

" That's tremendous, that's a delta, " he said, using the mathematical term for a

change.

The study randomized 595 patients to one of five arms:

Standard therapy with interferon and ribavirin, whose volunteers acted as

controls

A 28-week arm with all three drugs

A 28-week arm, starting with a four-week interferon/ribavirin lead-in, followed

by all three drugs for 24 weeks

A 48-week arm with all three drugs

And a 48-week arm starting with a four-week interferon/ribavirin lead-in,

followed by all three drugs for 44 weeks

The last arm has the investigators most excited, but all of the investigational

arms outperformed controls, although Dr. Kwo said the researchers will have to

wait for further analysis to see if the differences are statistically

significant.

It also seems clear, he said, the some patients will do well on the shorter arms

and " the challenge " will be to figure who will need the longer therapeutic

period.

It is also still not clear which patients will do better with the lead-in, he

said.

The two main adverse events that were linked to the drug were dysgeusia -- a bad

taste in the mouth -- and about a 0.5 to 1.0 gram per deciliter reduction in

hemoglobin levels in addition to the anemia caused by ribavirin.

" That's (the anemia) not concerning, but it's real, " he said.

Investigators looking at the other drug, telaprevir, are focusing on shorter

therapeutic durations, according to Stefan Zeuzem, M.D., of J.W. Goethe

University Hospital in furt, Germany.

Dr. Zeuzem reported that the final results of the so-called PROVE2 study,

conducted in Europe, show that the time for first undetectable level of

hepatitis RNA is markedly shortened by the addition of telaprevir to standard

medications.

Like the boceprevir trial, the PROVE2 study had several arms:

A control arm, in which 82 patients got a placebo plus pegylated interferon and

ribavirin for 12 weeks, followed by 36 weeks of interferon and ribivarin alone

An arm in which 78 patients got telaprevir and interferon alone for 12 weeks

An arm in which 82 patients got telaprevir plus interferon and ribavirin for 12

weeks

And an arm in which 81 patients got telaprevir plus interferon and ribavirin for

12 weeks, followed by interferon and ribavirin for another 12 weeks

The key efficacy result was that the two arms containing both telaprevir and

ribavirin did better at most time points than the control arm, Dr. Zeuzem said.

" The addition of ribavirin leads to better efficacy, " he said.

The sustained virological response of the two telaprevir/ribavirin arms was 60%

and 69%, respectively, compared with 46% for the control arm, Dr. Zeuzem

reported.

The difference was significant (at P=0.004) for the 24-week arm, but fell short

of significance for the 12-week arm, he said, although improvements in response

were significant at earlier times in the study.

The most common adverse events leading to stopping the trial were rash and

pruritis, all in the experimental arms, Dr. Zeuzem said. All told, 12 patients,

or 7%, discontinued all study drugs due to rash, which was typically

maculopapular exanthema.

Late-stage clinical trials for both drugs are under way.

The boceprevir study was sponsored by Schering-Plough. Dr. Kwo reported

financial links to Indenix, Human Genome Sciences, Merck, Novartis,

Schering-Plough, and Vertex.

The telaprevir study was sponsored by Vertex Pharmaceuticals. Dr. Zeuzem

reported financial links with Tibotec, Vertex, and Roche.

Primary source: Hepatology

Source reference:

Kwo P, et al " HCV SPRINT-1: Boceprevir plus Peginterferon alfa-2b/Ribavirin for

Treatment of Genotype 1 Chronic Hepatitis C in Previously Untreated Patients "

Hepatology 2008; 48(4): Abstract LB16.

Additional source: Hepatology

Source reference:

Zeuzem S, et al " Telaprevir in Combination with Peginterferon-Alfa-2a with or

without Ribavirin in the Treatment of Chronic Hepatitis C: Final Results of the

PROVE2 Study " Hepatology 2008; 48(4): Abstract 243