Adding Boceprevir Improves Virologic Response in Chronic HCV-1

Adding the protease inhibitor boceprevir to standard peginterferon-ribavirin therapy for chronic hepatitis C virus type 1 markedly improves the rate of sustained virologic response, according to two reports in the March 31 issue of the New England Journal of Medicine.

The rate of sustained virologic response to standard therapy alone is typically below 50% in these patients, and is even lower (30% or less) in certain groups such as patients of African heritage and those who relapsed after initial treatment. In these separate international phase III randomized clinical trials, the addition of boceprevir boosted that rate to as high as 75%.

Boceprevir was granted priority review status by the Food and Drug Administration earlier this year and has yet to be approved.

In the first trial, 1,097 previously untreated patients were randomly assigned to receive standard peginterferon-ribavirin therapy alone for 44 weeks (363 subjects); response-guided therapy in which peginterferon-ribavirin plus boceprevir were given for 24 weeks and then the standard therapy was continued, along with the addition of a placebo, for another 24 weeks only in those who had detectable HCV RNA levels (368 subjects); or fixed-duration therapy in which patients received 44 weeks of standard therapy plus oral boceprevir (366 subjects).

Because of the marked difference in treatment response between black and nonblack patients, the study cohort was further analyzed by race: 159 black and 938 nonblack subjects, said Dr. Fred Poordad of Cedars-Sinai Medical Center, Los Angeles, and his associates.

A sustained virologic response was attained in 67%-68% of the nonblack patients who received boceprevir, compared with only 40% of the nonblack patients who received standard therapy alone. This represents a relative increase of approximately 70%.

Among blacks, a sustained virologic response was attained in 42%-53% of those who received boceprevir, compared with only 23% of those who received standard therapy alone. This represents a relative increase of approximately 50%.

Both boceprevir regimens were associated with elevated rates of anemia, and nearly twice as many patients given boceprevir (43%) as control subjects (24%) required erythropoietin or showed a hemoglobin level of less than 9.5 g per dL. Dysgeusia also developed twice as often in patients given boceprevir.

However, "neither the incidence of serious adverse events nor the frequency of discontinuation owing to an adverse event differed significantly between patients receiving boceprevir and those receiving standard therapy," Dr. Poordad and his colleagues said (N. Engl. J. Med. 2011:364:1195-1206).

The use of the second drug regimen allowed the researchers to identify those patients who showed an early treatment response and could be spared from an additional unnecessary 24 weeks of treatment.

In the second study, 403 patients at 80 sites across North America and Europe were randomly assigned to receive standard peginterferon-ribavirin plus placebo for 44 weeks (80 subjects); a response-guided regimen in which standard peginterferon-ribavirin and boceprevir were given for 32 weeks and standard therapy was continued, with the addition of a placebo, for another 12 weeks only in those who had detectable HCV RNA levels (162 subjects); or fixed-duration standard therapy plus boceprevir for 44 weeks (161 subjects).

This study population was different from the first one in that it was particularly "hard to treat," involving patients who had either not responded to an initial course of treatment or who had relapsed after showing an initial response, said Dr. Bruce R. Bacon of Saint Louis University and his associates.

Again, the rates of sustained virologic response were 59%-66% in patients who received boceprevir, compared with only 21% in those who received standard treatment alone.

"The rates of sustained virologic response among patients with prior relapse were 29% in group 1, versus 69% and 75% in group 2 and group 3, respectively; among patients with prior nonresponse, the corresponding rates were 7% versus 40% and 52%," the investigators said (N. Engl. J. Med. 2011;364:1207-17).

"Notably, a sustained virologic response was achieved, after boceprevir was added to the standard of care, in 33%-34% of the patients with a poor response to interferon, as compared with 0% in the patients retreated with peginterferon-ribavirin alone," Dr. Bacon and his colleagues said.

As with Dr. Poordad’s study, the second regimen allowed the identification of patients who had an early treatment response and could safely refrain from an additional 12 weeks of therapy.

In this study, patients who received boceprevir had higher rates of serious adverse events and were more likely to discontinue the study medications or require dose modifications than those in the control group. The incidence of anemia was approximately twice as high with boceprevir as without it. Dysgeusia also was more frequent with boceprevir.

In both of these clinical trials, patients who showed undetectable levels of HCV RNA at week 8 also showed a high rate of sustained virologic response, regardless of which treatment they received. This confirms that a strong early response to treatment is predictive of a sustained virologic response, both groups of researchers said.

Both of these studies were funded by Schering-Plough (now part of Merck). Both groups of investigators reported ties to numerous industry sources, including Shering-Plough/Merck.

Adding the protease inhibitor boceprevir to standard peginterferon-ribavirin therapy for chronic hepatitis C virus type 1 markedly improves the rate of sustained virologic response, according to two reports in the March 31 issue of the New England Journal of Medicine.

The rate of sustained virologic response to standard therapy alone is typically below 50% in these patients, and is even lower (30% or less) in certain groups such as patients of African heritage and those who relapsed after initial treatment. In these separate international phase III randomized clinical trials, the addition of boceprevir boosted that rate to as high as 75%.

Boceprevir was granted priority review status by the Food and Drug Administration earlier this year and has yet to be approved.

In the first trial, 1,097 previously untreated patients were randomly assigned to receive standard peginterferon-ribavirin therapy alone for 44 weeks (363 subjects); response-guided therapy in which peginterferon-ribavirin plus boceprevir were given for 24 weeks and then the standard therapy was continued, along with the addition of a placebo, for another 24 weeks only in those who had detectable HCV RNA levels (368 subjects); or fixed-duration therapy in which patients received 44 weeks of standard therapy plus oral boceprevir (366 subjects).

Because of the marked difference in treatment response between black and nonblack patients, the study cohort was further analyzed by race: 159 black and 938 nonblack subjects, said Dr. Fred Poordad of Cedars-Sinai Medical Center, Los Angeles, and his associates.

A sustained virologic response was attained in 67%-68% of the nonblack patients who received boceprevir, compared with only 40% of the nonblack patients who received standard therapy alone. This represents a relative increase of approximately 70%.

Among blacks, a sustained virologic response was attained in 42%-53% of those who received boceprevir, compared with only 23% of those who received standard therapy alone. This represents a relative increase of approximately 50%.

Both boceprevir regimens were associated with elevated rates of anemia, and nearly twice as many patients given boceprevir (43%) as control subjects (24%) required erythropoietin or showed a hemoglobin level of less than 9.5 g per dL. Dysgeusia also developed twice as often in patients given boceprevir.

However, "neither the incidence of serious adverse events nor the frequency of discontinuation owing to an adverse event differed significantly between patients receiving boceprevir and those receiving standard therapy," Dr. Poordad and his colleagues said (N. Engl. J. Med. 2011:364:1195-1206).

The use of the second drug regimen allowed the researchers to identify those patients who showed an early treatment response and could be spared from an additional unnecessary 24 weeks of treatment.

In the second study, 403 patients at 80 sites across North America and Europe were randomly assigned to receive standard peginterferon-ribavirin plus placebo for 44 weeks (80 subjects); a response-guided regimen in which standard peginterferon-ribavirin and boceprevir were given for 32 weeks and standard therapy was continued, with the addition of a placebo, for another 12 weeks only in those who had detectable HCV RNA levels (162 subjects); or fixed-duration standard therapy plus boceprevir for 44 weeks (161 subjects).

This study population was different from the first one in that it was particularly "hard to treat," involving patients who had either not responded to an initial course of treatment or who had relapsed after showing an initial response, said Dr. Bruce R. Bacon of Saint Louis University and his associates.

Again, the rates of sustained virologic response were 59%-66% in patients who received boceprevir, compared with only 21% in those who received standard treatment alone.

"The rates of sustained virologic response among patients with prior relapse were 29% in group 1, versus 69% and 75% in group 2 and group 3, respectively; among patients with prior nonresponse, the corresponding rates were 7% versus 40% and 52%," the investigators said (N. Engl. J. Med. 2011;364:1207-17).

"Notably, a sustained virologic response was achieved, after boceprevir was added to the standard of care, in 33%-34% of the patients with a poor response to interferon, as compared with 0% in the patients retreated with peginterferon-ribavirin alone," Dr. Bacon and his colleagues said.

As with Dr. Poordad’s study, the second regimen allowed the identification of patients who had an early treatment response and could safely refrain from an additional 12 weeks of therapy.

In this study, patients who received boceprevir had higher rates of serious adverse events and were more likely to discontinue the study medications or require dose modifications than those in the control group. The incidence of anemia was approximately twice as high with boceprevir as without it. Dysgeusia also was more frequent with boceprevir.

In both of these clinical trials, patients who showed undetectable levels of HCV RNA at week 8 also showed a high rate of sustained virologic response, regardless of which treatment they received. This confirms that a strong early response to treatment is predictive of a sustained virologic response, both groups of researchers said.

Both of these studies were funded by Schering-Plough (now part of Merck). Both groups of investigators reported ties to numerous industry sources, including Shering-Plough/Merck.

Adding the protease inhibitor boceprevir to standard peginterferon-ribavirin therapy for chronic hepatitis C virus type 1 markedly improves the rate of sustained virologic response, according to two reports in the March 31 issue of the New England Journal of Medicine.

The rate of sustained virologic response to standard therapy alone is typically below 50% in these patients, and is even lower (30% or less) in certain groups such as patients of African heritage and those who relapsed after initial treatment. In these separate international phase III randomized clinical trials, the addition of boceprevir boosted that rate to as high as 75%.

Boceprevir was granted priority review status by the Food and Drug Administration earlier this year and has yet to be approved.

In the first trial, 1,097 previously untreated patients were randomly assigned to receive standard peginterferon-ribavirin therapy alone for 44 weeks (363 subjects); response-guided therapy in which peginterferon-ribavirin plus boceprevir were given for 24 weeks and then the standard therapy was continued, along with the addition of a placebo, for another 24 weeks only in those who had detectable HCV RNA levels (368 subjects); or fixed-duration therapy in which patients received 44 weeks of standard therapy plus oral boceprevir (366 subjects).

Because of the marked difference in treatment response between black and nonblack patients, the study cohort was further analyzed by race: 159 black and 938 nonblack subjects, said Dr. Fred Poordad of Cedars-Sinai Medical Center, Los Angeles, and his associates.

A sustained virologic response was attained in 67%-68% of the nonblack patients who received boceprevir, compared with only 40% of the nonblack patients who received standard therapy alone. This represents a relative increase of approximately 70%.

Among blacks, a sustained virologic response was attained in 42%-53% of those who received boceprevir, compared with only 23% of those who received standard therapy alone. This represents a relative increase of approximately 50%.

Both boceprevir regimens were associated with elevated rates of anemia, and nearly twice as many patients given boceprevir (43%) as control subjects (24%) required erythropoietin or showed a hemoglobin level of less than 9.5 g per dL. Dysgeusia also developed twice as often in patients given boceprevir.

However, "neither the incidence of serious adverse events nor the frequency of discontinuation owing to an adverse event differed significantly between patients receiving boceprevir and those receiving standard therapy," Dr. Poordad and his colleagues said (N. Engl. J. Med. 2011:364:1195-1206).

The use of the second drug regimen allowed the researchers to identify those patients who showed an early treatment response and could be spared from an additional unnecessary 24 weeks of treatment.

In the second study, 403 patients at 80 sites across North America and Europe were randomly assigned to receive standard peginterferon-ribavirin plus placebo for 44 weeks (80 subjects); a response-guided regimen in which standard peginterferon-ribavirin and boceprevir were given for 32 weeks and standard therapy was continued, with the addition of a placebo, for another 12 weeks only in those who had detectable HCV RNA levels (162 subjects); or fixed-duration standard therapy plus boceprevir for 44 weeks (161 subjects).

This study population was different from the first one in that it was particularly "hard to treat," involving patients who had either not responded to an initial course of treatment or who had relapsed after showing an initial response, said Dr. Bruce R. Bacon of Saint Louis University and his associates.

Again, the rates of sustained virologic response were 59%-66% in patients who received boceprevir, compared with only 21% in those who received standard treatment alone.

"The rates of sustained virologic response among patients with prior relapse were 29% in group 1, versus 69% and 75% in group 2 and group 3, respectively; among patients with prior nonresponse, the corresponding rates were 7% versus 40% and 52%," the investigators said (N. Engl. J. Med. 2011;364:1207-17).

"Notably, a sustained virologic response was achieved, after boceprevir was added to the standard of care, in 33%-34% of the patients with a poor response to interferon, as compared with 0% in the patients retreated with peginterferon-ribavirin alone," Dr. Bacon and his colleagues said.

As with Dr. Poordad’s study, the second regimen allowed the identification of patients who had an early treatment response and could safely refrain from an additional 12 weeks of therapy.

In this study, patients who received boceprevir had higher rates of serious adverse events and were more likely to discontinue the study medications or require dose modifications than those in the control group. The incidence of anemia was approximately twice as high with boceprevir as without it. Dysgeusia also was more frequent with boceprevir.

In both of these clinical trials, patients who showed undetectable levels of HCV RNA at week 8 also showed a high rate of sustained virologic response, regardless of which treatment they received. This confirms that a strong early response to treatment is predictive of a sustained virologic response, both groups of researchers said.

Both of these studies were funded by Schering-Plough (now part of Merck). Both groups of investigators reported ties to numerous industry sources, including Shering-Plough/Merck.