AASLD 2019公布ABI-H0731 phase 2a最终结果，Assembly股票上涨30%！

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ABI-H0731联合NA治疗有效降低HBV DNA, HBV RNA, HBeAg, HBcrAg和HBsAg

研究报告了用ABI-H0731+NA治疗24周的HBeAg+慢性hbv感染患者2a期的最终结果。在研究202（RX单纯患者）中，ABI-H0731+NA（恩替卡韦）与恩替卡韦单独治疗相比，HBV DNA（5.27 vs 3.99；P=0.017）和RNA（2.34 vs0.61；P<0.001）的平均log10下降幅度更大。在研究201（NA经治患者）中，ABI-H0731+NA与NA单独达到未检测到的DNA靶点（TND）的患者比例分别为69%与0%（P<0.001），达到RNA<35U/ml且基线时RNA≥35U/ml的患者比例分别为52%与0%（P=0.0013）。在研究211中，有64名HBeAg+患者目前正在接受超过24周的延长治疗。在研究201中接受ABI-H0731+NA的27名HBeAg+患者中，41%（11/27）的患者现在已经获得DNA TND，同时RNA<35u/ml和HBeAg<1 IU/ml。在他们最后的时间点，研究202中的22名患者（n=22）的平均DNA和RNA分别下降了6.1和3.0 log，HBeAg平均下降0.6log（11例≥0.5log，4例≥1.0log），HBcrAg平均下降0.8log（7例≥1.0log，3例≥2.0log），HBsAg的平均下降0.4log（7例≥0.5log，3例≥1.0log）。ABI-H0731在治疗长达1年的患者中显示出良好的安全性和耐受性，只有轻度/中度不良事件和实验室异常，只有一例因1级皮疹而停药。ABI-H0731+NA的联合导致HBV DNA和RNA比NA单独治疗下降的更快和更多，以及cccDNA (pgRNA, HBeAg and HBcrAg)库的耗竭和HBsAg的持续下降。

Finalresults from Phase 2a are reported for HBeAg+ patients with chronic HBVinfection treated with 731+Nrtl for 24 weeks. In Study 202 (Rx naïve patients),greater mean log10 declines in HBV DNA (5.27 vs 3.99; p=0.017) and RNA (2.34 vs0.61; p<0.001) were achieved with 731+Nrtl (entecavir) versus entecaviralone. In Study 201 (Nrtl-suppressed patients), the proportion of patients on731+Nrtl versus Nrtl alone achieving DNA target not detected (TND) was 69% vs0% (p<0.001), and the proportion of patients achieving RNA <35 U/mL whoseRNA was ≥35 U/mL at baseline was 52% vs 0% (p=0.0013) respectively. In Study211, there are 64 HBeAg+ patients currently on extended treatment beyond 24weeks. Among the 27 HBeAg+ patients receiving 731+Nrtl in Study 201, 41%(11/27) have now achieved DNA TND along with RNA <35 U/mL and HBeAg <1IU/mL. At their last timepoint, Study 202 patients now in Study 211 (n=22) havedemonstrated mean DNA and RNA declines of 6.1 and 3.0 logs, respectively, withobserved mean log changes of ≥0.6 for HBeAg (11 patients ≥0.5, 4 patients≥1.0), >0.8 log for HBcrAg (7 patients ≥1.0, 3 patients ≥2.0) and ≥0.4 logfor HBsAg (7 patients ≥0.5, 3 patients ≥1.0). 731 continues to exhibit afavorable safety and tolerability profile in patients treated for up to 1 year,with only mild/moderate adverse events and lab abnormalities, and only a singlediscontinuation due to a Grade 1 rash. The combination of 731+NrtI results infaster and deeper declines in HBV DNA and RNA than NrtI alone, as well assubsequent declines in the surrogate markers of cccDNA (pgRNA, HBeAg andHBcrAg) predictive of cccDNA pool depletion, and HBsAg. The emergent datasupports the continued development of 731. Abstract data are as of the time ofsubmission; the poster is expected to include updated safety and efficacyresults.

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