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Interim Results From Boceprevir Phase II Study In Genotype 1 Treatment-Naive Hepatitis C Patients Presented At EASL

27 Apr 2008


Schering-Plough Corporation (NYSE: SGP) reported that results from a planned interim analysis of an ongoing Phase II study of boceprevir, its investigational oral hepatitis C protease inhibitor, in 595 treatment-naive patients with chronic hepatitis C virus (HCV) genotype 1 were presented at the 43rd Annual Meeting of the European Association for the Study of the Liver (EASL). The ongoing study evaluates boceprevir in 28-week and 48-week treatment regimens.

In a 28-week treatment regimen in which patients received 4 weeks of PEGINTRON(TM) (peginterferon alfa-2b) and REBETOL(R) (ribavirin, USP) prior to the addition of boceprevir (800 mg TID), the rate of sustained virological response at 12 weeks after the end of treatment (SVR 12) was 57 percent (ITT).(1-3) Importantly, this treatment regimen provided an indication of early predictability of response, with patients who had undetectable virus (HCV-RNA) in plasma after 4 weeks of boceprevir treatment achieving an SVR 12 rate of 86 percent.

"These interim results are very encouraging, especially given the response seen with a shorter course of therapy in a difficult-to-treat patient population," said principal investigator Paul Kwo, M.D., associate professor of medicine and medical director, liver transplantation, Department of Medicine, Division of Gastroenterology/Hepatology, Indiana University School of Medicine, Indianapolis, who presented the data. "Boceprevir has been well tolerated by patients in this study, including in the longer duration treatment arms, and we look forward to further results from this ongoing study."

Overall, 77 percent of the 595 patients in the study were enrolled in the United States. African-Americans represent 16 percent of the patients enrolled and 7 percent of patients in the study are cirrhotic.

In the ongoing study, known as HCV SPRINT-1 (HCV Serine Protease Inhibitor Therapy-1), boceprevir (800 mg TID) is being evaluated in three treatment regimens: 4 weeks of PEGINTRON (1.5 mcg/kg once weekly) and REBETOL (800-1400 mg daily based on patient weight) therapy followed by the addition of boceprevir to the combination for 24 or 44 weeks (totaling 28 or 48 weeks of treatment); boceprevir in combination with PEGINTRON and REBETOL at the doses described above for 28 or 48 weeks (triple combination); and boceprevir in combination with PEGINTRON and low-dose REBETOL (400-1000 mg daily) for 48 weeks, compared to a control of PEGINTRON (1.5 mcg/kg once weekly) and REBETOL (800-1400 mg daily based on patient weight) alone for 48 weeks (an approved treatment regimen). The primary endpoint of the study is sustained virologic response after 24 weeks of follow up.

During a late-breaker oral presentation at EASL, Dr. Kwo presented interim results for the two 28-week boceprevir arms of the study. For patients receiving 4 weeks of PEGINTRON and REBETOL therapy prior to the addition of boceprevir, SVR 12 was 57 percent (59/103), compared to 55 percent (59/107) for patients in the boceprevir triple combination arm. For patients in these two boceprevir arms who had undetectable virus (HCV-RNA) after 4 weeks of boceprevir treatment (RVR), the SVR 12 rates were 86 percent (53/62) and 74 percent (31/42), respectively. SVR 12 rates are not yet available for patients in the 48-week boceprevir arms or the 48-week control arm, as treatment of these patients is ongoing.

Safety data from the study showed that the most common adverse events reported in the boceprevir arms were fatigue, anemia, nausea and headache. No increase in skin adverse events (rash or pruritus) beyond what was seen in the PEGINTRON and REBETOL control arm was observed. Treatment discontinuations due to adverse events were between 11 and 15 percent for patients in the boceprevir arms, compared to 8 percent for the control arm.

Early response rates at week 4 (RVR) and week 12 (EVR) of boceprevir treatment were increased for patients who received 4 weeks of PEGINTRON and REBETOL therapy prior to the administration of boceprevir (62 and 79 percent, respectively), compared to patients in the triple combination (38 and 69 percent) and control (8 and 34 percent) arms, respectively. In the 28-week boceprevir arms, these patients also had a reduction in viral breakthrough compared to patients in the triple combination arm (4 vs. 7 percent, respectively).

"The results seen with this novel treatment paradigm will influence the design of our future clinical studies, as we plan to consider RVR at week 4 of boceprevir treatment as the criterion for determining which patients can receive a shorter course of boceprevir therapy and which patients should continue treatment for 48 weeks," said Robert J. Spiegel, M.D., chief medical officer and senior vice president, Schering-Plough Research Institute. "Additionally, this strategy has the potential to reduce the likelihood of the development of resistance by identifying patients who are responders to interferon and ribavirin prior to their receiving a protease inhibitor."

The rationale for this novel treatment regimen is based on the fact that both PEGINTRON and REBETOL reach steady-state concentrations by week 4, so patients have the protease inhibitor added at a time when the backbone drug levels have been optimized. In addition, the patient's immune system will have been activated and primed by PEGINTRON at the time that boceprevir is added to the regimen. This approach may minimize the period of time when there is a "functional monotherapy" with a direct antiviral, potentially reducing the likelihood for the development of resistance.

The HCV SPRINT-1 study is currently ongoing at sites across the United States, Canada and Europe. Final results from the study are anticipated to be available in early 2009, and will be submitted for presentation at an appropriate medical meeting.
9 Responses
Avatar universal
Lots of good info here...

About Hepatitis C

Hepatitis C is a serious and potentially life-threatening disease. It is the most common blood-borne infection in America and Europe, and the most common form of liver disease, affecting nearly 5 million people in the United States, 5 million in Europe and some 200 million people worldwide. It is the leading cause of cirrhosis and liver cancer, and the number one reason for liver transplants in the United States and Europe.


In the United States, PEGINTRON is indicated for use alone or with ribavirin for the treatment of chronic hepatitis C in patients with compensated liver disease who have not been previously treated with interferon alpha and who are at least 18 years of age.

Important Safety Information Regarding U.S. Labeling for PEGINTRON and REBETOL

Alpha interferons, including PEGINTRON and INTRON(R) A, may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be monitored closely with periodic clinical and laboratory evaluations. Patients with persistently severe or worsening signs or symptoms of these conditions should be withdrawn from therapy. In many, but not all cases, these disorders resolve after stopping PEGINTRON and/or INTRON A therapy.

Use with Ribavirin: Ribavirin may cause birth defects and/or death of the unborn child. Extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients. Ribavirin causes hemolytic anemia. The anemia associated with REBETOL therapy may result in a worsening of cardiac disease. Ribavirin is genotoxic and mutagenic and should be considered a potential carcinogen.


PEGINTRON is contraindicated in patients with hypersensitivity to PEGINTRON or any other component of the product, autoimmune hepatitis, and hepatic decompensation (Child-Pugh score greater than 6 [class B and C]) in cirrhotic CHC patients before or during treatment. INTRON A (Interferon alfa-2b, recombinant) for Injection is contraindicated in patients with hypersensitivity to INTRON A or any component of the product, autoimmune hepatitis, and decompensated liver disease. PEGINTRON or INTRON A in combination with REBETOL therapy is additionally contraindicated in patients with hypersensitivity to ribavirin or any other component of the product, women who are pregnant, men whose female partners are pregnant, patients with hemoglobinopathies (e.g., thalassemia major, sickle-cell anemia), and patients with creatinine clearance less than 50 mL/min.

Avoid Pregnancy

REBETOL therapy should not be started until a report of a negative pregnancy test has been obtained immediately prior to planned initiation of therapy. Extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients during therapy and 6 months post-treatment. Patients should use at least two effective forms of contraception and have monthly pregnancy tests during therapy and for 6 months after completion of therapy. A Ribavirin Pregnancy Registry has been established to monitor maternal-fetal outcomes of pregnancies in female patients and female partners of male patients exposed to ribavirin during treatment, and for 6 months following cessation of treatment.

Incidence of Adverse Events

There are no new adverse events specific to PEGINTRON as compared to INTRON A; however, the incidence of some (e.g., injection site reactions, fever, rigors, nausea) were higher. The most common adverse events associated with PEGINTRON were "flu-like" symptoms, occurring in approximately 50% of patients, which may decrease in severity as treatment continues. Application site disorders were common (47%), but all were mild (44%) or moderate (4%) and no patient discontinued, and included injection site inflammation and reaction (i.e., bruise, itchiness, irritation). Injection site pain was reported in 2% of patients receiving PEGINTRON. Alopecia (thinning of the hair) is also often associated with alpha interferons including PEGINTRON.

Psychiatric adverse events, which include insomnia, were common (57%) with PEGINTRON but similar to INTRON A (58%). Depression was most common at 29%. Suicidal behavior including ideation, suicidal attempts, and completed suicides occurred in 1% of patients during or shortly after completing treatment with PEGINTRON.

The following serious or clinically significant adverse events have been reported at a frequency less than 1% with PEGINTRON or interferon alpha: Severe decreases in neutrophil or platelet counts, hypothyroidism, hyperglycemia, hypotension, arrhythmia, ulcerative and hemorrhagic colitis, development or exacerbation of autoimmune disorders including thyroiditis, RA, systemic lupus erythematosus, psoriasis, pulmonary disorders (dyspnea, pulmonary infiltrates, pneumonitis and pneumonia, some resulting in patient deaths), urticaria, angioedema, bronchoconstriction, anaphylaxis, retinal hemorrhages, and cotton wool spots.

In the PEGINTRON/REBETOL combination trial, the incidence of serious adverse events was 17% in the PEGINTRON/REBETOL groups compared to 14% in the INTRON A/ REBETOL group. The incidence of severe adverse events in the PEGINTRON/REBETOL combination therapy trial was 23% in the INTRON A/REBETOL group and 31-34% in the PEGINTRON/REBETOL groups. Dose reductions due to adverse reactions occurred in 42% of patients receiving PEGINTRON (1.5 mcg/kg)/REBETOL and in 34% of those receiving INTRON A/REBETOL.

In a study with weight-based ribavirin, there was a higher rate of anemia among patients in the weight-based dosing group (29%) compared to the flat-dosing group (19%). The majority of these cases were mild and responded to dose reductions. Serious adverse events were similar between the two groups (12%), and discontinuations for adverse events (15% in weight-based dosing and 14% in flat dosing) were also similar. Dose modifications due to adverse events occurred more frequently in the weight-based dosing group (29%) compared to the flat-dosing (23%) group.
Avatar universal
Some really good news here.....

"For patients in these two boceprevir arms who had undetectable virus (HCV-RNA) after 4 weeks of boceprevir treatment (RVR), the SVR 12 rates were 86 percent (53/62) and 74 percent (31/42), respectively. SVR 12 rates are not yet available for patients in the 48-week boceprevir arms or the 48-week control arm, as treatment of these patients is ongoing."
Avatar universal
Just noticed the date is from 2008, I only saw April 27 and thought it was today.
Avatar universal
Here ya go....


UPDATE 2-Schering hepatitis C drug shines, but anemia seen
Thu Apr 23, 2009 11:09am EDT

* Virus undetectable in 75 pct of treated patients

* Best response seen for any drug in mid-stage trials

* But anemia seen in half of treated patients

* 39 to 51 pct of treated patients needed EPO for anemia

By Ransdell Pierson

NEW YORK, April 23 (Reuters) - A Schering-Plough Corp (SGP.N) drug knocked the hepatitis C virus down to undetectable levels in three-fourths of patients in a mid-stage study, twice the effectiveness seen with standard treatments, researchers said on Thursday.

But half the patients taking the boceprevir experimental medicine developed anemia -- a potential commercial disadvantage to a similar pill called telaprevir that Vertex Pharmaceutical Inc (VRTX.O) is developing.

Both drugs work through a new mechanism -- by blocking a protein called protease that the virus needs to replicate -- and are considered potential big-selling products. As many as 4 million Americans are believed to be infected with the virus, the leading reason for liver transplants.

Results of the Phase II boceprevir trial, involving 595 patients who were infected with the virus but had not previously been treated, were presented in Copenhagen at the annual meeting of the European Association for the Study of the Liver. Patients had genotype 1, the most common form of the virus.

During the first month of the study, all patients received the two standard hepatitis C treatments sold by Schering-Plough -- a long-acting form of interferon called Pegintron and the anti-viral pill ribavirin.

One group of patients then added boceprevir to Pegintron and ribavirin for 44 weeks, while another group took only Pegintron and ribavirin over the same period.

After the 48-week trial concluded, 75 percent of those in the boceprevir group had a sustained virologic response (SVR) -- meaning undetectable levels of virus.

"This is the highest sustained virologic response reported for any Phase II study of patients with genotype 1," said Dr. Paul Kwo, an associate professor at Indiana University School of Medicine, the study's chief investigator.

By contrast, only 38 percent of patients who did not get boceprevir drove the virus down to undetectable levels in the same 48-week period.

Researchers also determined that after only 28 weeks of treatment with boceprevir, Pegintron and ribavirin, 56 percent of patients achieved SVR.

Anemia was seen in about half of patients taking boceprevir, and in a third of patients taking only Pegintron and ribavirin.

page 2

Erythropoietin (EPO), a widely used anemia treatment, was used by 39 percent to 51 percent of patients taking boceprevir, and by 26 percent of those taking only Pegintron and ribavirin.

"Management of anemia with EPO is a common practice in hepatitis C treatment today," said Kwo, who noted that ribavirin and protease inhibitors both increase the risk of anemia.

A lesser incidence of anemia was reported last year for Vertex' rival telaprevir in mid-stage trials -- ranging from 29 to 37 percent of patients. Telaprevir knocked the virus to undetectable levels in about two thirds of patients.

Kwo, who has also tested the Vertex product, said data from late-stage trials of boceprevir and telaprevir will provide a clearer indication of relative anemia risk for the two new protease inhibitors.

Geoffrey Porges, a biotech analyst for Sanford Bernstein who is attending the Copenhagen meeting, said the need to take EPO to control anemia will hurt boceprevir.

"It would be very unusual for a drug to go forward and more or less require the use of another drug that's not even approved for that indication," Porges said.

Boceprevir is considered one of the most important of Schering-Plough's experimental drugs. Merck & Co (MRK.N) will inherit the pill when it completes its planned purchase of Schering later this year.

Shares of Merck were down 0.57 percent to $22.85, while Schering-Plough fell 0.14 percent to $21.64, both in late morning trading on the New York Stock Exchange.

(Additional reporting by Bill Berkrot) (Reporting by Ransdell Pierson; Editing by Lisa Von Ahn and Gunna Dickson)
Avatar universal
Thanks Willy... That's what I was looking for.
Avatar universal

Presentation Date: Apr 23, 2009

P. Kwo1, E. Lawitz2, J. McCone3, E. Schiff4, J. Vierling5, D. Pound6, M. Davis7, J. Galati8, S. Gordon9, N. Ravendhran10, L. Rossaro11, F. Anderson12, I. Jacobson13, R. Rubin14, K. Koury15, C. Brass15, E. Chaudhri15, J. Albrecht15
1Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, 2Alamo Medical Research, San Antonio, TX, 3Mount Vernon Endoscopy Center, Alexandria, VA, 4Center for Liver Diseases, University of Miami Miller School of Medicine, Miami, FL, 5Professor of Medicine and Surgery, Baylor College of Medicine, Houston, TX, 6Indianapolis Gastroenterology Research Foundation, Indianapolis, IN, 7Digestive Care/South Florida Center of Gastroenterology, Wellington, FL, 8Liver Specialists of Texas, Houston, TX, 9Department of Hepatology, Henry Ford Health Systems, Detroit, MI, 10Digestive Disease Associates, Baltimore, MD, 11Internal Medicine, University of California-Davis Medical Center, Sacramento, CA, USA, 12The Liver & Intestinal Research Center, Vancouver, BC, Canada, 13Weill Cornell Medical College, New York, NY, 14Digestive Healthcare of Georgia, Atlanta, GA, 15Schering-Plough Research Institute, Kenilworth, NJ, USA

Background: HCV SPRINT-1 assessed the safety and efficacy of boceprevir, an oral inhibitor of HCV-NS3 protease, plus PegIntron (P) (1.5 µg/kg/QW) and ribavirin (R) (400-1400 mg/day).
Methods: P/R(800-1400 mg/day) for 48 weeks compared to five boceprevir(800 mg TID) regimens: 4 weeks of P/R lead-in followed by P/R(800-1400 mg/day)/boceprevir for 24 or 44 weeks; P/R(800-1400 mg/day)/boceprevir for 28 or 48 weeks; and P/low-dose R(400-1000 mg/day)/boceprevir for 48 weeks. The primary endpoint was sustained virologic response (SVR) at 24 weeks post-treatment (Roche TaqMan LLD=15 IU/mL).
Results: Of 595 patients treated in US (77%), Canada and Europe, 60% were male, 16% Black, 7% cirrhotic, 56% genotype 1a and 89% had high viral load (>600,000 IU/mL). SVR was significantly increased in the 28 and 48 week boceprevir arms compared to P/R Control. RVR† and EVR†† were highly predictive of SVR with boceprevir combinations. Rash-related AEs were similar for boceprevir regimens and P/R Control.

   Sustained Viriologic Response %
PLEASE NOTE:  This is a very complex table; Impossible to post.  Visit the above link.  Willy

Conclusions: Both 28 and 48 week boceprevir regimens significantly increased SVR with very low relapse rates in 48 week regimens. However, low dose ribavirin with PegIntron and boceprevir was associated with increased viral breakthrough, relapse and lower efficacy. In contrast, P/R lead-in prior to boceprevir substantially increased SVR and reduced viral breakthrough.
Avatar universal
No problemo, glad to help and I know many people are interested in this study.  Looks like they did a good job with it.  It should help a lot of people and who knows, maybe having Vertex having some tight competition will help keep the cost down for all of us.  : )

Glad to see your good results on the trial.

Avatar universal
Thanks again, my hope is to stop treatment at the 28 week mark. Here is copy/paste from another site, 66% achieved RVR with four week lead in.

"SPRINT-1 shows that boceprevir therapy can be tailored to the needs of individual patients and their response rates. "If the viral decline is sharp [and] becomes undetected in the first 4 weeks of boceprevir, which occurred in two thirds of patients (week 8 of total treatment), then the cure rates are between 82% and 94%, respectively, in the 28- and 48-week treatment groups, suggesting that the majority of patients treated with boceprevir will be treated for 28 weeks, Dr. Kwo pointed out. "But if the patient is a slow responder due to low interferon sensitivity or other reasons . . . and you clear the virus between weeks 4 and 12 of boceprevir, then continuing on for 48 weeks maximizes your chance of cure."
Avatar universal
Here is also some really good news for cirrhotic's, from the same web site.

"He illustrated this in cirrhotic patients who are very difficult to treat. Dr. explained that "50% of cirrhotic patients achieved SVR on the boceprevir combination, which is higher than the 40% rate for noncirrhotic patients on standard therapy."

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