雅培HCV药物治疗99％SVR4新数据

StephenW

Subject: NATAP: Abbott HCV 4-Drug Regimen 99% SVR4 New Data


        Press Release                    Abbott's Investigational Interferon-Free Hepatitis C Treatment Regimen Achieved SVR12 (Observed Data) Rates in 99 Percent of Treatment-Naïve and 93 Percent in Prior Null Responders for Genotype 1 Patients in Phase 2b Study
新闻稿
雅培的​​研究干扰素无C型肝炎治疗方案实现SVR12（观测数据）之前空应答的基因1型患者在治疗初治和93％的99％的价格在第2b期研究

                    
                        October 15, 2012
                Abbott Park, Illinois (NYSE: ABT) — Abbott today announced initial results from "Aviator," a phase 2b study of its interferon-free, investigational regimen for the treatment of hepatitis C (HCV). Initial results show sustained virological response at 12 weeks post treatment (SVR12) in 99 percent of treatment-naïve (n=77) and 93 percent of null responders (n=41) for genotype 1 (GT1) HCV patients taking a combination of ABT-450/r, ABT-267, ABT-333 and ribavirin for 12 weeks, based on an observed data analysis.
Full results from the study will be presented at the Latebreaker Session of The Liver Meeting, the Annual Meeting of the American Association for the Study of Liver Disease (AASLD) in Boston, November 9-13. Abstracts are available at www.aasld.org.
The observed data analysis used in this abstract does not include six patients who had not yet reached post-treatment week 12 or had missing values (data points) at the time of the abstract submission. All virologic failures and safety discontinuations were included in the analysis.


2012年10月15日，

雅培公园，伊利诺伊州（NYSE：ABT） - 雅培今天宣布，“飞行者”，一个2b期研究，用于治疗丙型肝炎病毒（HCV）干扰素，研究方案的初步结果。初步结果显示，99％的治疗初治组（n = 77）和93％的空应答组（n = 41），HCV基因型1（GT1）患者在12周的治疗后（SVR12）在持续病毒学应答相结合的ABT -450 / R，ABT-267 ABT-333和利巴韦林治疗12周后，观察到的数据分析的基础上。
"There is a significant unmet medical need for genotype 1, the most common form of HCV in the U.S. and Europe," said Kris Kowdley, M.D., director of the Liver Center of Excellence in the Digestive Disease Institute at Virginia Mason Medical Center, and Clinical Professor of Medicine at the University of Washington in Seattle. "Results from this phase 2b study suggest that sustained virological response can be achieved without interferon in a high proportion of genotype-1 patients, including patients who have not responded to previous treatment. This is exciting news as we continue to study treatment options for patients."
"Based on the promising results we've seen, Abbott has selected a triple direct acting antiviral regimen, with and without ribavirin for phase 3 development," said Scott Brun, M.D., divisional vice president, Infectious Disease Development, Abbott. "The ability to show sustained virological response in these patient populations, without the use of interferon, is extremely encouraging."
Study M11-652 (Aviator)

• Kris Kowdley, et al.; Monday, November 12 (3:00-3:15 p.m. ET)
  "A 12-Week Interferon-free Treatment Regimen with ABT-450/r, ABT-267, ABT-333 and Ribavirin Achieves SVR12 Rates (Observed Data) of 99% in Treatment-Naïve Patients and 93% in Prior Null Responders with HCV Genotype1 Infection"
  

The objective of this phase 2b study was to assess the safety, and efficacy of ABT-450/r (dosed 100/100 to 200/100mg QD), ABT-267 (25mg QD), ABT-333 (400mg BID) and ribavirin in non-cirrhotic treatment-naïve patients and prior peg-interferon/ribavirin null responders for 8, 12 or 24 weeks.
Enrollment was open to GT1-infected patients regardless of IL28B host genotype and ribavirin dosing was weight-based.
The 12-week regimen of three direct acting antivirals plus ribavirin had the highest SVR12 rates among the 8 and 12 week arms. Results from the 12 week treatment groups containing three direct acting antivirals plus ribavirin are summarized in the chart below.

	Treatment-naïve (N=79)	Null responders(N=45)
BL HCV RNA (log10 IU/mL)	6.5±0.6	6.6±0.5
BL IL28B non-CC genotype	72%	96%
SVR4	78/79 (99%)	42/45 (93%)
OD SVR12	76/77 (99%)	38/41 (93%)
PTW12 data missing*	2	4
Breakthrough	0	3
Relapse	1	0
OD SVR12 (GT1a)	52/53 (98%)	24/27 (89%)
OD SVR12 (GT1b)	24/24 (100%)	14/14 (100%)
OD SVR12 (IL28B non-CC)	54/55 (98%)	36/39 (92%)

*	Did not follow up (2 treatment-naïve patients and 1 null responder) or have not yet reached PTW12 (3 null responders)

Additional data presented in the abstract represent all 8- and 12-week arms (n=448) of this 14-arm study (571 patients enrolled: 438 treatment-naïve and 133 prior null responders). SVR12 rates for other 8- and 12-week regimens ranged from 89-92 percent. Complete SVR12 data for 8- and 12-week arms will be presented at the Liver Meeting.
Four of 448 patients (one percent) in the 8- and 12-week arms discontinued due to adverse events. Of five serious AEs (1 percent), 1 (arthralgia or joint pain) was possibly study drug-related. In the trial, the most common adverse events were fatigue (28 and 27 percent) and headache (28 and 31 percent) for treatment naïve and null responders respectively.
Abbott Data at AASLDIn addition to Aviator, there are four poster presentations on Abbott's investigational medicines for the treatment of HCV:

• Tami Pilot-Matias et al.; Sunday, November 11 (8:00 a.m.-5:30 p.m. ET)
  "Characterization of Resistant Variants in NS3 and NS5B Detected in Subjects Treated with ABT-450/r, Ribavirin, and Either ABT-072 or ABT-333 in the Pilot and Co-Pilot Studies Who Experienced Virologic Breakthrough or Relapse"
• Preethi Krishnan et al.; Tuesday, November 13 (8:00 a.m.-12:00 p.m. ET)
  "Antiviral Activity and Resistance Profiles for ABT-267, a Novel HCV NS5A Inhibitor, In Vitro and During 3-Day Monotherapy in HCV Genotype-1 (GT1)-Infected Treatment-Naïve Subjects"
• Lane Kirbach et al.; Tuesday, November 13 (8:00 a.m.-12:00 p.m. ET)
  "Evaluation of Patient Preferences for Treatment Outcomes in Hepatitis C Virus (HCV)"
• Amit Khatri et al.; Sunday, November 11 (8:00 a.m.-5:30 p.m. ET)
  "Pharmacokinetics and Safety of Co-administered ABT-450 plus Ritonavir (ABT-450/r), ABT-267 and ABT-333 as a Single Dose in Subjects with Normal Hepatic Function and in Subjects with Mild, Moderate and Severe Hepatic Impairment"