2014年3月4日訊 /生物谷BIOON/ --目前，艾伯維（AbbVie）正穩(wěn)步推進其丙肝雞尾酒療法。在第21屆逆轉(zhuǎn)錄病毒和機會性感染大會（CROI 2014）上，該公司公布的關(guān)鍵III期M13-961（PEARL-III）研究的詳實數(shù)據(jù)表明，其所開發(fā)的丙肝雞尾酒療法對難治性丙肝群體的治愈率幾乎達到了100%。
AbbVie開發(fā)的丙肝雞尾酒療法由固定劑量ABT-450/ritonavir/ABT-267（150mg/100mg/25mg，每日一次）和ABT-333（250mg，每日2次）有或無利巴韋林（基于體重，每日2次）組成。ABT-450、ABT-267、ABT-333三者分別具有不同的作用機制，能夠中斷HCV復(fù)制過程，
PEARL-III研究僅是AbbVie丙肝雞尾酒療法臨床項目的6個III期研究之一，該公司預(yù)計于下一季度向FDA提交監(jiān)管文件。而競爭對手吉利德（Gilead）已在2月份向FDA提交了其雞尾酒療法（ledipasvir/sofosbuvir）的監(jiān)管文件。雙方均預(yù)計在今年將各自的丙肝雞尾酒療法推向市場。不過，值得注意的是，這2家公司在其2014年指南中均未提及各自雞尾酒療法的銷售預(yù)期。
關(guān)于PEARL-III研究：
PEARL-III是一項全球性、多中心、隨機、雙盲、安慰劑對照研究，在初治（treatment-naive）非肝硬化基因型1b HCV成人感染者中開展，評估了AbbVie丙肝雞尾酒療法單獨及聯(lián)合利巴韋林（RBV）用于為期12周治療的療效和安全性。
該項研究包含419名無肝硬化證據(jù)的初治基因型1b感染者，209名患者隨機分配接受12周的雞尾酒療法（無利巴韋林），210名患者接受12周的雞尾酒療法和利巴韋林治療。接受雞尾酒療法（無利巴韋林）的患者組有99.0%（n=207/209）的患者在治療12周后實現(xiàn)了持續(xù)病毒學(xué)應(yīng)答（SVR12），雞尾酒+利巴韋林組有99.5%（n=209/210）的患者實現(xiàn)SVR12。雞尾酒療法（無利巴韋林）治療組以安慰劑代替利巴韋林。
該項研究達到了主要重點和次要終點。同時，在治療后12周內(nèi)，未記載到任何病情復(fù)發(fā)病例。
英文原文：AbbVie's hep C cocktail aces its latest PhIII study with a sky-high cure rate
BOSTON, March 3, 2014 /PRNewswire/ -- The first detailed results from AbbVie's (NYSE: ABBV) pivotal phase III study, PEARL-III, were presented today as part of the 21st Conference on Retroviruses and Opportunistic Infections (CROI) press conference and will also be presented as a late-breaker at the conference on March 4. PEARL-III evaluated the efficacy and safety of 12 weeks of treatment with AbbVie's investigational therapy with or without ribavirin (RBV) in non-cirrhotic, adult patients with chronic genotype 1b (GT1b) hepatitis C virus (HCV) infection who were new to treatment.
The PEARL-III study met its primary and secondary endpoints. In the 419-patient study, sustained virologic response rates 12 weeks post-treatment (SVR12) of 99.5 and 99.0 percent were achieved with the AbbVie regimen with and without RBV, respectively. There were no study drug discontinuations due to adverse events.
"Results from PEARL-III are encouraging, as they demonstrate AbbVie's regimen can achieve high rates of SVR, with and without ribavirin across several patient characteristics in those with genotype 1b chronic hepatitis C infection," said Peter Ferenci, M.D., professor of Gastroenterology and Hepatology, Medical University of Vienna.
PEARL-III enrolled patients across different demographics and characteristics. Response rates in patients with certain characteristics (male gender, Black race and IL28B non-CC genotypes) were examined, as these patient populations have historically been associated with having a decreased response to treatment. High response rates were observed across all patients in the study, including those with these characteristics.
"We are excited about the strong PEARL-III results which demonstrate the AbbVie regimen achieved high SVR rates with no discontinuations due to adverse events in patients new to treatment with genotype 1b infection," said Scott Brun, M.D., vice president, pharmaceutical development, AbbVie. "Additionally, with these data, we continue to be on track to begin major regulatory submissions in the second quarter of 2014. AbbVie will continue to disclose additional detailed phase III study results at future scientific congresses and in publications."
About Study M13-961 (PEARL-III)
PEARL-III is a global, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of 12 weeks of treatment with AbbVie's regimen with and without RBV in non-cirrhotic, GT1b HCV-infected, treatment-naive adult patients.
The study population consisted of 419 GT1b treatment-naive patients with no evidence of liver cirrhosis: 209 patients randomized to the regimen without RBV for 12 weeks, and 210 patients randomized to the regimen with RBV for 12 weeks. Following 12 weeks of treatment, 99.0 percent receiving the regimen without RBV (n=207/209) and 99.5 percent receiving the regimen with RBV (n=209/210) achieved SVR12. Patients in the treatment arm without RBV received placebo in substitution for RBV.
Patients with different demographics and characteristics were enrolled in the study, including gender, race (Black vs. non-Black), Hispanic/Latino ethnicity, age, geographic region, body mass index (BMI), liver fibrosis stage, IL28B genotype and viral load.
Across treatment arms in PEARL-III, there were no documented relapses within 12 weeks post-treatment. No on-treatment virologic failures occurred in the treatment arm without RBV and a single virologic failure occurred in the treatment arm with RBV. While all patients in the study completed therapy, two patients in the arm without RBV were lost to follow-up and therefore were considered treatment failures.
The most commonly reported adverse events (>10 percent for either arm) were headache, fatigue, pruritus, nausea and asthenia, with pruritus and nausea occurring at a statistically higher rate in the treatment arm with RBV compared to the arm without RBV. Anemia occurred more commonly among patients in the RBV-containing arm with clinically significant anemia requiring RBV dose reductions occurring in 9 percent of these patients.
Additional information about AbbVie's phase III studies can be found on www.clinicaltrials.gov.
About AbbVie's Investigational HCV Regimen
The AbbVie investigational regimen consists of the fixed-dose combination of ABT-450/ritonavir (150/100mg) co-formulated with ABT-267 (25mg), dosed once daily, and ABT-333 (250mg) with or without RBV (weight-based), dosed twice daily. The combination of three different mechanisms of action interrupts the HCV replication process with the goal of optimizing SVR rates across different patient populations.
AbbVie's HCV Development Program
The AbbVie HCV clinical development program is intended to advance scientific knowledge and clinical care by investigating an interferon-free, all-oral regimen with and without RBV with the goal of producing high SVR rates in as many patients as possible, including those that typically do not respond well to treatment, such as previous non-responders to interferon-based therapy or patients with advanced liver fibrosis or cirrhosis.
ABT-450 was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals (NASDAQ: ENTA) for HCV protease inhibitors and regimens that include protease inhibitors. ABT-450 is being developed by AbbVie for use in combination with AbbVie's other investigational medicines for the treatment of HCV.
Safety Information for Ribavirin and Ritonavir
Ribavirin and ritonavir are not approved for the investigational use discussed above, and no conclusions can or should be drawn regarding the safety or efficacy of these products for this use.
There are special safety considerations when prescribing these drugs in approved populations.
Ritonavir must not be used with certain medications due to significant drug-drug interactions and in patients with known hypersensitivity to ritonavir or any of its excipients.
Ribavirin monotherapy is not effective for the treatment of chronic hepatitis C virus and must not be used alone for this use. Ribavirin causes significant teratogenic effects and must not be used in women who are pregnant or breast-feeding and in men whose female partners are pregnant. Ribavirin must not be used in patients with a history of severe pre-existing cardiac disease, severe hepatic dysfunction or decompensated cirrhosis of the liver, autoimmune hepatitis, hemoglobinopathies, or in combination with peginterferon alfa-2a in HIV/HCV co-infected patients with cirrhosis and Child-Pugh score greater than or equal to 6.
See approved product labels for more information.
About AbbVie
AbbVie is a global, research-based biopharmaceutical company formed in 2013 following separation from Abbott Laboratories. The company's mission is to use its expertise, dedicated people and unique approach to innovation to develop and market advanced therapies that address some of the world's most complex and serious diseases. AbbVie employs approximately 25,000 people worldwide and markets medicines in more than 170 countries.
