현재 많은 새로운 C형간염의 치료제들이 개발되고 있습니다. 현재 페그인터페론과 리바비린의 병용 치료는 부작용도 많고 치료효과도 비교적 낮아 새로운 약제의 출현을 모두 손꼽아 기다리고 있습니다.
이중 길리어드 제약사의 “소포스부비어(Sofosbuvir)” 라는 약의 성과가 눈에 띕니다.
아마도 부작용이 많은 페그인터페론 주사 없이 C형간염을 치료하는 날이 멀지 않은 것 같습니다.
세계에서 가장 권위있는 의학 논문 저널인 New England Journal of Medicine에 2013년 올해에 들어서만 소포스부비어(Sofosbuvir)에 대한 논문이 6편 실렸습니다.
Nucleotide Polymerase Inhibitor Sofosbuvir plus Ribavirin for Hepatitis C (N Engl J Med 2013; 368:34-44January 3, 2013)
Exploratory Study of Oral Combination Antiviral Therapy for Hepatitis C (N Engl J Med 2013; 368:45-53January 3, 2013)
Sofosbuvir for Previously Untreated Chronic Hepatitis C Infection (N Engl J Med 2013; 368:1878-1887May 16, 2013)
Sofosbuvir for Hepatitis C Genotype 2 or 3 in Patients without Treatment Options (N Engl J Med 2013; 368:1867-1877May 16, 2013)
Current and Future Therapies for Hepatitis C Virus Infection (N Engl J Med 2013; 368:1907-1917May 16, 2013)
HCV Treatment — No More Room for Interferonologists? (N Engl J Med 2013; 368:1931-1932May 16, 2013)
연구마다 치료 성과가 조금씩 차이 있지만 C형간염 유전자형 2, 3형의 경우 소포스부비어와 리바비린(ribavirin) 두 가지 먹는 약으로만 12주만 치료해도 100% 치료 성과를 달성했다고 보고 하고 있습니다.
유전자형 1형에서도 현재 치료제인 페그인터페론 주사와 리바비린에 소포스부비어를 추가해 3약제로 병합 치료할 경우 12주만 치료해도 90% 치료 성과를 달성했다고 보고 하고 있습니다.
서양인들에서 기존 페그인터페론 주사와 리바비린 치료로 55% 정도 치료되었던 것에 비하면 놀라운 치료 효과이고, 치료가 더 잘 되는 한국인에서는 정말 희망적이라 예측할 수 있겠습니다.
미국 식약청(FDA)이 올해 내 (12월) 로 우선 심사한다고 하니 빠르면 올 연말, 늦어도 내년이면 미국에서는 치료할 수 있을 것 같습니다.
우리나라는 2012년 미국에서 C형간염 1형 치료제로 승인된 텔라프레비어(telaprevir), 보세프레비어(boceprevir)도 아직 언제 사용 가능할지 확실치 않은 상황인데,
이 두 약제보다 훨씬 더 뛰어난 효과, 치료 기간의 단축, 낮은 부작용를 보이고 1형뿐 아니라 2, 3형에도 효과적인 “소포스부비어“가 나온다면 C형간염 치료 효과, 치료 기간, 치료 부작용 등에서 획기적 변화가 올 것 같습니다.
올해 겨울에 C형 간염 치료의 가이드라인이 새로 개정되어 발표될 예정입니다. 효과가 좋고 부작용이 적은 새로운 약물에 대한 내용이 실리길 기대합니다.
하루 빨리 미국에서도 승인이 이루어지고 한국에서도 사용가능한 날이 오기를 기대합니다.
Sofosbuvir for Previously Untreated Chronic Hepatitis C Infection
Eric Lawitz, M.D., Alessandra Mangia, M.D., David Wyles, M.D., Maribel Rodriguez-Torres, M.D., Tarek Hassanein, M.D., Stuart C. Gordon, M.D., Michael Schultz, M.D., Ph.D., Mitchell N. Davis, D.O., Zeid Kayali, M.D., K. Rajender Reddy, M.D., Ira M. Jacobson, M.D., Kris V. Kowdley, M.D., Lisa Nyberg, M.D., G. Mani Subramanian, M.D., Ph.D., Robert H. Hyland, D.Phil., Sarah Arterburn, M.S., Deyuan Jiang, Ph.D., John McNally, Ph.D., Diana Brainard, M.D., William T. Symonds, Pharm.D., John G. McHutchison, M.D., Aasim M. Sheikh, M.D., Zobair Younossi, M.D., M.P.H., and Edward J. Gane, M.D.
N Engl J Med 2013; 368:1878-1887May 16, 2013DOI: 10.1056/NEJMoa1214853
Background
In phase 2 trials, the nucleotide polymerase inhibitor sofosbuvir was effective in previously untreated patients with chronic hepatitis C virus (HCV) genotype 1, 2, or 3 infection.
Methods
We conducted two phase 3 studies in previously untreated patients with HCV infection. In a single-group, open-label study, we administered a 12-week regimen of sofosbuvir plus peginterferon alfa-2a and ribavirin in 327 patients with HCV genotype 1, 4, 5, or 6 (of whom 98% had genotype 1 or 4). In a noninferiority trial, 499 patients with HCV genotype 2 or 3 infection were randomly assigned to receive sofosbuvir plus ribavirin for 12 weeks or peginterferon alfa-2a plus ribavirin for 24 weeks. In the two studies, the primary end point was a sustained virologic response at 12 weeks after the end of therapy.
Results
In the single-group study, a sustained virologic response was reported in 90% of patients (95% confidence interval, 87 to 93). In the noninferiority trial, a sustained response was reported in 67% of patients in both the sofosbuvir–ribavirin group and the peginterferon–ribavirin group. Response rates in the sofosbuvir–ribavirin group were lower among patients with genotype 3 infection than among those with genotype 2 infection (56% vs. 97%). Adverse events (including fatigue, headache, nausea, and neutropenia) were less common with sofosbuvir than with peginterferon.
Conclusions
In a single-group study of sofosbuvir combined with peginterferon–ribavirin, patients with predominantly genotype 1 or 4 HCV infection had a rate of sustained virologic response of 90% at 12 weeks. In a noninferiority trial, patients with genotype 2 or 3 infection who received either sofosbuvir or peginterferon with ribavirin had nearly identical rates of response (67%). Adverse events were less frequent with sofosbuvir than with peginterferon. (Funded by Gilead Sciences; FISSION and NEUTRINO ClinicalTrials.gov numbers, NCT01497366 and NCT01641640, respectively.)
Sofosbuvir for Hepatitis C Genotype 2 or 3 in Patients without Treatment Options
Ira M. Jacobson, M.D., Stuart C. Gordon, M.D., Kris V. Kowdley, M.D., Eric M. Yoshida, M.D., Maribel Rodriguez-Torres, M.D., Mark S. Sulkowski, M.D., Mitchell L. Shiffman, M.D., Eric Lawitz, M.D., Gregory Everson, M.D., Michael Bennett, M.D., Eugene Schiff, M.D., M. Tarek Al-Assi, M.D., G. Mani Subramanian, M.D., Ph.D., Di An, Ph.D., Ming Lin, Ph.D., John McNally, Ph.D., Diana Brainard, M.D., William T. Symonds, Pharm.D., John G. McHutchison, M.D., Keyur Patel, M.D., Jordan Feld, M.D., M.P.H., Stephen Pianko, M.D., Ph.D., and David R. Nelson, M.D.
N Engl J Med 2013; 368:1867-1877May 16, 2013DOI: 10.1056/NEJMoa1214854
Background
Patients chronically infected with hepatitis C virus (HCV) genotype 2 or 3 for whom treatment with peginterferon is not an option, or who have not had a response to prior interferon treatment, currently have no approved treatment options. In phase 2 trials, regimens including the oral nucleotide polymerase inhibitor sofosbuvir have shown efficacy in patients with HCV genotype 2 or 3 infection.
Methods
We conducted two randomized, phase 3 studies involving patients with chronic HCV genotype 2 or 3 infection. In one trial, patients for whom treatment with peginterferon was not an option received oral sofosbuvir and ribavirin (207 patients) or matching placebo (71) for 12 weeks. In a second trial, patients who had not had a response to prior interferon therapy received sofosbuvir and ribavirin for 12 weeks (103 patients) or 16 weeks (98). The primary end point was a sustained virologic response at 12 weeks after therapy.
Results
Among patients for whom treatment with peginterferon was not an option, the rate of a sustained virologic response was 78% (95% confidence interval [CI], 72 to 83) with sofosbuvir and ribavirin, as compared with 0% with placebo (P<0.001). Among previously treated patients, the rate of response was 50% with 12 weeks of treatment, as compared with 73% with 16 weeks of treatment (difference, −23 percentage points; 95% CI, −35 to −11; P<0.001). In both studies, response rates were lower among patients with genotype 3 infection than among those with genotype 2 infection and, among patients with genotype 3 infection, lower among those with cirrhosis than among those without cirrhosis. The most common adverse events were headache, fatigue, nausea, and insomnia; the overall rate of discontinuation of sofosbuvir was low (1 to 2%).
Conclusions
In patients with HCV genotype 2 or 3 infection for whom treatment with peginterferon and ribavirin was not an option, 12 or 16 weeks of treatment with sofosbuvir and ribavirin was effective. Efficacy was increased among patients with HCV genotype 2 infection and those without cirrhosis. In previously treated patients with genotype 3 infection, 16 weeks of therapy was significantly more effective than 12 weeks. (Funded by Gilead Sciences; POSITRON and FUSION ClinicalTrials.gov numbers, NCT01542788 and NCT01604850, respectively.)
Current and Future Therapies for Hepatitis C Virus Infection
T. Jake Liang, M.D., and Marc G. Ghany, M.D., M.H.Sc.
N Engl J Med 2013; 368:1907-1917May 16, 2013DOI: 10.1056/NEJMra1213651
Only 20 years after the discovery of the hepatitis C virus, a cure is now likely for most people with chronic infection. This review considers current therapy and the present landscape of drug development for hepatitis C.
Dr. Ghany reports receiving payment for manuscript preparation from Clinical Care Options. No other potential conflict of interest relevant to this article was reported.
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
We thank Dr. Leonard Seeff for his critical review and helpful comments on an earlier draft of the manuscript; and the staff members of the Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, for their support and assistance.
Nucleotide Polymerase Inhibitor Sofosbuvir plus Ribavirin for Hepatitis C
Edward J. Gane, M.D., Catherine A. Stedman, M.B., Ch.B., Ph.D., Robert H. Hyland, D.Phil., Xiao Ding, Ph.D., Evguenia Svarovskaia, Ph.D., William T. Symonds, Pharm.D., Robert G. Hindes, M.D., and M. Michelle Berrey, M.D., M.P.H.
N Engl J Med 2013; 368:34-44January 3, 2013DOI: 10.1056/NEJMoa1208953
Background
The standard treatment for hepatitis C virus (HCV) infection is interferon, which is administered subcutaneously and can have troublesome side effects. We evaluated sofosbuvir, an oral nucleotide inhibitor of HCV polymerase, in interferon-sparing and interferon-free regimens for the treatment of HCV infection.
Methods
We provided open-label treatment to eight groups of patients. A total of 40 previously untreated patients with HCV genotype 2 or 3 infection were randomly assigned to four groups; all four groups received sofosbuvir (at a dose of 400 mg once daily) plus ribavirin for 12 weeks. Three of these groups also received peginterferon alfa-2a for 4, 8, or 12 weeks. Two additional groups of previously untreated patients with HCV genotype 2 or 3 infection received sofosbuvir monotherapy for 12 weeks or sofosbuvir plus peginterferon alfa-2a and ribavirin for 8 weeks. Two groups of patients with HCV genotype 1 infection received sofosbuvir and ribavirin for 12 weeks: 10 patients with no response to prior treatment and 25 with no previous treatment. We report the rate of sustained virologic response 24 weeks after therapy.
Results
Of the 40 patients who underwent randomization, all 10 (100%) who received sofosbuvir plus ribavirin without interferon and all 30 (100%) who received sofosbuvir plus ribavirin for 12 weeks and interferon for 4, 8, or 12 weeks had a sustained virologic response at 24 weeks. For the other patients with HCV genotype 2 or 3 infection, all 10 (100%) who received sofosbuvir plus peginterferon alfa-2a and ribavirin for 8 weeks had a sustained virologic response at 24 weeks, as did 6 of 10 (60%) who received sofosbuvir monotherapy. Among patients with HCV genotype 1 infection, 21 of 25 previously untreated patients (84%) and 1 of 10 with no response to previous therapy (10%) had a sustained virologic response at 24 weeks. The most common adverse events were headache, fatigue, insomnia, nausea, rash, and anemia.
Conclusions
Sofosbuvir plus ribavirin for 12 weeks may be effective in previously untreated patients with HCV genotype 1, 2, or 3 infection. (Funded by Pharmasset and Gilead Sciences; ClinicalTrials.gov number
Exploratory Study of Oral Combination Antiviral Therapy for Hepatitis C
Fred Poordad, M.D., Eric Lawitz, M.D., Kris V. Kowdley, M.D., Daniel E. Cohen, M.D., Thomas Podsadecki, M.D., Sara Siggelkow, R.N., Michele Heckaman, M.S., Lois Larsen, Ph.D., Rajeev Menon, Ph.D., Gennadiy Koev, Ph.D., Rakesh Tripathi, M.S., Tami Pilot-Matias, Ph.D., and Barry Bernstein, M.D.
N Engl J Med 2013; 368:45-53January 3, 2013DOI: 10.1056/NEJMoa1208809
Background
There is a need for interferon-free treatment regimens for hepatitis C virus (HCV) infection. The goal of this study was to evaluate ABT-450, a potent HCV NS3 protease inhibitor, combined with low-dose ritonavir (ABT-450/r), in addition to ABT-333, a nonnucleoside NS5B polymerase inhibitor, and ribavirin, for the treatment of HCV infection.
Methods
We conducted a 12-week, phase 2a, open-label study involving patients who had HCV genotype 1 infection without cirrhosis. All patients received ABT-333 (400 mg twice daily) and ribavirin (1000 to 1200 mg per day) and one of two daily doses of ABT-450/r. Groups 1 and 2 included previously untreated patients; group 1 received 250 mg of ABT-450 and 100 mg of ritonavir, and group 2 received 150 mg and 100 mg, respectively. Group 3, which included patients who had had a null or partial response to previous therapy with peginterferon and ribavirin, received daily doses of 150 mg of ABT-450 and 100 mg of ritonavir. The primary end point was an undetectable level of HCV RNA from week 4 through week 12 (extended rapid virologic response).
Results
A total of 17 of the 19 patients in group 1 (89%) and 11 of the 14 in group 2 (79%) had an extended rapid virologic response; a sustained virologic response 12 weeks after the end of treatment was achieved in 95% and 93% of the patients, respectively. In group 3, 10 of 17 patients (59%) had an extended rapid virologic response, and 8 (47%) had a sustained virologic response 12 weeks after therapy; 6 patients had virologic breakthrough, and 3 had a relapse. Adverse events included abnormalities in liver-function tests, fatigue, nausea, headache, dizziness, insomnia, pruritus, rash, and vomiting.
Conclusions
This preliminary study suggests that 12 weeks of therapy with a combination of a protease inhibitor, a nonnucleoside polymerase inhibitor, and ribavirin may be effective for treatment of HCV genotype 1 infection. (Funded by Abbott; ClinicalTrials.gov number
