DECEMBER 2010 • WWW.FAMILYPRACTICENEWS.COM INFECTIOUS DISEASES 29 Telaprevir, Boceprevir Improved HCV Cure Rates

BY DIANA MAHONEY arm with undetectable HCV underwent a similar 4-week standard Major Finding: The HCV protease inhibitors RNA at study weeks 8 and 12 therapy lead-in strategy as defined above, FROM THE ANNUAL MEETING OF THE telaprevir and boceprevir improve sustained followed by the addition of placebo for AMERICAN ASSOCIATION FOR virologic response rates and shorten treat- was 36 weeks, whereas those THE STUDY OF LIVER DISEASES ment duration in patients with chronic he- patients in whom HCV RNA 44 more weeks or by the addition of bo-

VITALS patitis C virus infection. was detectable at study week 8, ceprevir, either for 24 more weeks for pa- tients with undetectable HCV RNA at BOSTON – The forthcoming availabili- Data Source: Four phase III clinical trials but undetectable at study week ty of the protease inhibitors telaprevir and evaluating the safety and efficacy of the di- 12, stopped boceprevir at week week 8 or for 24 more weeks plus 20 ad- boceprevir for the treatment of chronic rect-acting antivirals in treatment-naive and 36 but continued standard ther- ditional weeks of standard therapy for hepatitis C is likely to vastly improve vi- treatment-resistant HCV patients. apy for an additional 12 weeks, patients with detectable HCV RNA at rologic response rates and cut treatment Disclosures: Dr. Jacobson and Dr. Sherman for a total treatment duration week 8, but not at week 24, Dr. Poordad times, but experts warn that such ad- disclosed relationships with Vertex Pharma- of 48 weeks, Dr. Bacon said. explained. Patients with detectable HCV vancements need to be balanced against ceuticals, which manufactures telaprevir. Patients in the control group RNA at week 24 were discontinued for the “huge potential” for misuse of the Dr. Jacobson also has a relationship with were treated for 48 weeks. futility, he said. agents and the need to manage side effects Tibotec, which also is involved with the de- The SVR rates at 24 weeks “In both the response-guided and fixed- and monitor for antiviral resistance. velopment of telaprevir. Dr. Poordad and Dr. after treatment conclusion treatment arms, boceprevir increased vi- When used in combination with stan- Bacon also disclosed relationships with were significantly higher in the ral cure rates significantly, by approxi- dard therapy of pegylated interferon plus Merck, which manufactures boceprevir. boceprevir groups, compared mately 70%,” he said. Specifically, the ribavirin-based therapy, both of these in- with the control group. In the SVR rate was 63% in the 28-week re- vestigational drugs improved sustained The phase III, open-label ILLUMI- response-guided and fixed-duration bo- sponse-guided group, 66% in the 48-week virologic response rates and reduced NATE trial was designed to determine ceprevir groups, the SVR rates were 59% fixed-duration group, and 38% in the 48- treatment duration, compared with stan- whether extending the telaprevir and and 66%, respectively, compared with week control group, he said. dard therapy alone, in four pivotal, phase standard therapy regimen from 24 to 48 21% in the control patients, he said. In a cohort analysis of treatment re- III trials reported at the meeting. weeks would be beneficial in treatment- In all study arms, “previous relapsers sponse for the study’s 159 black pa- naive, genotype 1 HCV patients who and previous null responders fared bet- tients, the relative improvement in SVR Telaprevir Boosts Viral Cure Rates achieved extended RVR. In all, 540 pa- ter than prior nonresponders,” Dr. Bacon rates remained significantly improved In the ADVANCE trial, a three-arm, dou- tients were initially treated with the 12- said, noting that the respective SVR rates in the boceprevir arms, although the ble-blind, placebo-controlled study, in- week telaprevir regimen described for previous relapsers, null responders, differences were not as robust, Dr. Po- vestigators compared two telaprevir- above. Of the 352 patients who achieved and nonresponders were 29%, 7%, and ordad said. In this subgroup, the re- based regimens with standard therapy in RVR, 322 remained on treatment and 0% in the control group; 69%, 40%, and spective SVR rates in the response-guid- 1,088 treatment-naive patients with were randomized to either a 24-week or 33% in the response-guided therapy ed therapy, fixed-duration therapy, and chronic genotype 1 hepatitis C virus 48-week treatment arm. group; and 75%, 52%, and 34% in the control groups were 42%, 53%, and (HCV) infection, according to lead in- “The [SVR] rates associated with the fixed-duration group. 23%, respectively. vestigator Dr. Ira M. Jacobson of New 24-week and the 48-week arms were Boceprevir with a standard therapy The rationale for using a lead-in strat- York Weill Cornell Medical Center in statistically similar, at 92% and 87.5%, re- lead-in strategy was also evaluated in the egy “is to help physicians identify patient New York City. spectively,” reported Dr. Kenneth E. SPRINT-2 study involving HCV geno- responsiveness to interferon before Patients in treatment arms 1 and 2 re- Sherman of the University of Cincin- type 1 treatment-naive patients, accord- adding boceprevir,” Dr. Poordad ex- ceived 750 mg of telaprevir plus standard nati. Analyses of the data based on race ing to Dr. Fred Poordad of Cedars-Sinai plained. This can provide an early indi- therapy for 8 and 12 weeks, respectively, and extent of liver damage showed that Medical Center in Los Angeles. cation of the likelihood of treatment whereas patients in the control group re- 88% of black patients who experienced The trial included 1,097 patients who success. ■ ceived standard therapy alone, which extended RVR achieved SVR in both consisted of 180 mcg/week of pegylat- the 24- and 48-week treatment arms, and ed interferon alfa-2a and 1,000-1,200 82% and 88% of patients with advanced The Potential for Misuse Is ‘Huge’ mg/day of ribavirin. fibrosis/cirrhosis achieved SVR in the Patients who achieved extended, rapid 24-week and 48-week arms, respective- n the next year, “we are going to lead-in [even though the lead-in strat- virologic response (RVR) – defined as un- ly, he said. Isee the approval of two direct- egy was evaluated for boceprevir, detectable HCV RNA viral load at treat- The high viral cure rate observed in acting antiviral drugs – telaprevir not telaprevir], and other patients ment weeks 4 and 12 – were treated with the study – the overall SVR rate was 72% and boceprevir. We anticipate the might be put on boceprevir for 12 standard therapy for an additional 16 and in an intent-to-treat analysis – “[sup- widespread use of these weeks with no lead-in.” 12 weeks in the 8- and 12-week telapre- ports] the role of response-guided ther- drugs in the United States For optimal safety and vir arms, respectively, for a total of 24 apy with telaprevir-based regimens” in and the European Union, efficacy, physicians must weeks, Dr. Jacobson explained. Patients in treatment-naive patients,” he said. as they’ve been shown to have a good understand- whom HCV RNA was detectable at ei- improve sustained viro- ing of the treatment regi- ther week 4 or 12 received an additional Boceprevir Benefits Nonresponders logic response rates by ap- mens, particularly in spe- 40 and 36 weeks of therapy, respectively, Response-guided, fixed-duration therapy proximately 75% in treat- cial populations, and they for a total of 48 weeks, he said. with boceprevir was safe and effective in ment-naive patients,” Dr. must actively and fre- VIEW ON THE NEWS Compared with 44% of patients in a cohort of HCV genotype 1 patients Paul Pockros said at the quently monitor for an- the control group who achieved sus- who were enrolled in the RESPOND-2 meeting. tiviral resistance. Addi- tained virologic responses (SVR) 24 study and who failed standard therapy, Unfortunately, there is also a tionally, physicians should anticipate weeks after the last treatment, signifi- reported lead investigator Dr. Bruce R. “huge potential” for misuse of these problems with adherence, which is cantly more patients in both telaprevir Bacon of St. Louis University. drugs, owing to prescribing physi- already an issue for some patients on arms – 69% of the 8-week group and The 403 patients included those in cians’ poor understanding of the standard therapy, he said. 75% of the 12-week group – met that whom prior standard therapy induced no therapeutic populations, inadequate The objective should be “to keep end point, Dr. Jacobson reported. notable decrease in HCV viral load (null viral-assay testing, poor side-effect our eyes on the ball,” said Dr. Pock- The extended RVR rates in the 8- and responders) or a “not undetectable” de- management, and lack of monitor- ros. “Our primary goal moving for- 12-week groups were 57% and 58%, re- crease in HCV viral load (nonrespon- ing for antiviral resistance, he said. ward with all of the new drugs is go- spectively, compared with 8% in the con- ders), as well as those in whom prior The designs of the trials on which ing to be eradicating the virus.” trol arm, he said. treatment initially resulted in unde- approval will be based, as well as the Significantly improved SVRs were also tectable HCV RNA, followed by a viral resulting treatment regimens, are PAUL J. POCKROS, M.D., is head of observed in difficult-to-treat subgroups, rebound (relapsers), he said. fairly complex, said Dr. Pockros, “so the division of gastroenterology/ according to Dr. Jacobson. All the patients underwent a 4-week there will be lots of opportunities to hepatology at the Scripps Clinic in La “Among black patients, the [SVR] rates lead-in phase of standard therapy fol- screw things up.” For example, he Jolla, Calif. He disclosed relationships were 58% and 62% in the 8- and 12-week lowed by a random assignment to con- hypothesized, “I am sure that some with Vertex and Tibotec, which are treatment arms, and 25% in the control tinue standard therapy alone or in con- patients are going to be put on involved in the development of arm, and in cirrhotic patients the re- junction with 800 mg of boceprevir telaprevir for 44 weeks with a 4- telaprevir, and Merck, which spective rates were 53%, 62%, and 33%,” taken three times daily. The treatment week pegylated interferon/ribavirin manufactures boceprevir. he reported. duration for patients in the boceprevir