研究表明与研究药物实现了乙肝提高安全性结果

StephenW

Studies demonstrate improved safety results achieved with investigational drug for hep B
Tenofovir alafenamide improves patient safety while sustaining efficacy in patients with chronic Hepatitis B compared to tenofovir disoproxil fumarate

Date:
    April 15, 2016
Source:
    European Association for the Study of the Liver
Summary:
    Studies demonstrate that tenofovir alafenamide (TAF) improves patient safety while maintaining efficacy in patients with chronic hepatitis B virus (HBV) infection compared to tenofovir disoproxil fumarate (Viread, TDF).

FULL STORY

Studies presented today at The International Liver Congress™ 2016 in Barcelona, Spain, demonstrate that tenofovir alafenamide (TAF) improves patient safety while maintaining efficacy in patients with chronic Hepatitis B virus (HBV) infection compared to tenofovir disoproxil fumarate (Viread, TDF).

The studies demonstrate that regardless of Hepatitis B e antigen status (HBeAg*), 25mg of TAF once-daily was as effective as, and safer than, 300mg of TDF once-daily, with fewer negative changes in bone and kidney parameters.

Approximately 14 million people within the WHO EU Region are chronically infected with Hepatitis B.1 TAF is an investigational treatment for HBV and is approved as a component of a fixed-dose combination (Genvoya, E/C/F/TAF) for HIV infection. TDF is an approved treatment option for both HIV and HBV. TDF can cause severe side effects, including bone and renal toxicities.2

"These two studies demonstrate that treatment with tenofovir alafenamide is as effective and yet safer than treatment with tenofovir disoproxil fumarate," said Dr Maria Buti, Hospital General Universitari Vall d'Hebron, Barcelona, Spain, and lead author of one of the studies. "Patients with HBV require long-term treatment and we are pleased that these results could provide a potentially safer treatment regimen in the future."

The two randomised, double-blind Phase 3 trials are being conducted over a period of 96 weeks. Patients were randomised to TAF 25mg daily or to TDF 300mg daily and the primary efficacy endpoint was the percent of patients with HBV DNA below 29 IU/mL at week 48. The key safety endpoints were changes in hip and spine bone mineral density (a measure of minerals mainly calcium in bones), changes in serum creatinine (a waste product in blood that is removed by healthy kidneys) and dipstick proteinuria (protein excreted in urine). Markers of bone formation and resorption, and renal tubular function were also assessed in both studies.

In the study of HBeAg-negative patients, 94% (268 of 285) of patients receiving TAF and almost 93% (130 of 140) of patients receiving TDF achieved the primary endpoint. In the study of HBeAg-positive patients, almost 64% (371 of 581) of patients receiving TAF and almost 67% (195 of 292) of patients receiving TDF achieved the primary endpoint. Overall, the response rates in both studies met the primary endpoint of non-inferiority of TAF compared to TDF.

In both studies, patients receiving TAF experienced a significantly smaller mean percentage decrease from baseline in hip and spine bone mineral density at week 48 (p<0.001), and had smaller changes in renal tubular markers (p<0.001) than TDF. In the HBeAg-positive study, a smaller increase in serum creatinine was observed in patients receiving TAF (p=0.02). Additionally, the median change in estimated glomerular filtration rate (eGFR) from baseline to week 48 favoured TAF in both studies (p<0.01). The rates of treatment discontinuations and serious adverse events were low and similar in the two arms of both studies.

"While tenofovir disoproxil fumarate is an effective treatment option for patients with chronic Hepatitis B, we are pleased that this treatment, TAF, could provide patients with an equally effective and yet safer treatment option," said Professor Tom Hemming Karlsen, EASL Vice Secretary.

* HBeAg a sign that the virus is actively replicating in the body and that the infection is worse

References

1 Patient. Hepatitis B. Available from: http://patient.info/doctor/hepatitis-b-pro. Last accessed: March 2016.

2 AIDS Info. Tenofovir Disoproxil Fumarate. Available from: https://aidsinfo.nih.gov/drugs/2 ... fumarate/0/patient. Last accessed: March 2016.

Story Source:

The above post is reprinted from materials provided by European Association for the Study of the Liver.

StephenW

研究表明与研究药物实现了乙肝提高安全性结果
替诺福韦alafenamide改善患者的安全性，同时相比于富马酸替诺福韦酯的患者中慢性乙型肝炎的疗效维持

日期：
    2016年4月15日
资源：
    欧洲协会肝脏的研究
概要：
    研究表明，替诺福韦alafenamide（TAF）提高了患者的安全性，同时保持在慢性乙型肝炎病毒功效（HBV）感染相比富马酸替诺福韦酯（Viread的，TDF）。

全文

今天在国际肝病会议™2016年在西班牙巴塞罗那提出了研究，证明了替诺福韦alafenamide（TAF），提高​​了患者的安全，同时保持对慢性乙型肝炎病毒（HBV）感染的功效，与富马酸替诺福韦酯（Viread的，TDF）。

的研究表明，不管乙型肝炎e抗原状态（e抗原*），TAF每日一次25mg的是一样有效，并且比更安全，TDF每日一次，以在骨和肾参数较少负变化为300mg。

世界卫生组织欧盟地区内约14亿人患有慢性感染肝炎B.1 TAF是乙肝病毒的调查性治疗，并批准为固定剂量复合剂（Genvoya，E / C / F / TAF）艾滋病毒感染的一个组成部分。 TDF是HIV和HBV批准的治疗选择。 TDF可引起严重的副作用，包括骨和肾toxicities.2

“这两项研究表明，替诺福韦alafenamide治疗同样有效，但比富马酸替诺福韦酯治疗更安全，”玛丽亚·布提医生，医院一般Universitari瓦勒d'Hebron城，西班牙巴塞罗那，和其中的一个研究的主要作者。 “患者乙肝需要长期治疗，我们很高兴，这些结果可能在未来提供一个可能更安全的治疗方案。”

这两个随机，双盲三期临床试验正在一段96周进行的。患者每天或以每日TDF为300mg和主要疗效终点被随机TAF为25mg为患者低于29国际单位/毫升的HBV DNA的百分比在48周的关键安全终点是在髋关节和脊柱的骨矿物质密度的变化（测量矿物质主要是钙在骨骼中）的，血清肌酐（血液中的废物由健康的肾脏移除）和油尺蛋白尿（尿蛋白排出体外）的变化。的骨形成和骨吸收，以及肾小管功能标志物还评估了这两项研究。

在接受TDF患者HBeAg阴性患者，接受TAF患者94％（285 268），几乎93％（140 130）的研究达到了主要终点。在HBeAg阳性患者的研究中，接受TAF患者近64％（581 371），几乎67％（292 195）接受TDF患者达到主要终点。总体而言，在这两项研究的反应率满足TAF的非劣效性相比TDF的主要终点。

在两项研究中，接受TAF患者经历了从基线48周（P <0.001）一较小显著平均百分比减少髋部和脊柱骨密度，并曾在肾小管标志TDF相比变化较小（P <0.001）。在HBeAg阳性的研究中，患者中观察到接受TAF（P = 0.02），血清肌酐升幅收窄。此外，在估计肾小球滤过率（eGFR）从基线到48周位数的变化在两个研究（P <0.01）青睐TAF。治疗停药和严重不良事件的发生率很低，这两项研究的两臂相似。

“虽然富马酸替诺福韦酯是治疗慢性乙肝的有效治疗方案，我们很高兴，这种治疗，TAF，可以为患者提供一种同样有效，但更安全的治疗选择，”汤姆·海明卡尔森教授，EASL副局长说。

* HBeAg的一个迹象，表明病毒正在积极在体内的感染更糟糕的是复制

参考

1患者。乙型肝炎可从：http://patient.info/doctor/hepatitis-b-pro。最后访问时间：2016年3月。

2艾滋病资讯。富马酸替诺福韦酯。可从以下https://aidsinfo.nih.gov/drugs/2 ... -fumarate/0/patient。最后访问时间：2016年3月。

故事来源：

上述职位由欧洲协会肝病研究学会提供的材料转载。

StephenW

Tenofovir alafenamide exhibits similar efficacy, safety to Viread in HBV
April 15, 2016

  

BARCELONA — Tenofovir alafenamide was safe and showed non-inferior efficacy rates to Viread in hepatitis B e antigen-positive patients, according to phase 3 study results presented in a general session at International Liver Congress.
See Also

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“If patients want long-term therapy, I think [tenofovir alafenamide] is the better option,” Henry L-Y Chan, MD, director of the Digestive Disease Institute at The Chinese University of Hong Kong in China, said during his presentation.

Henry L-Y Chan, MD

Henry L-Y Chan

Chan and colleagues assigned 873 hepatitis B e antigen (HBeAg)-positive chronic HBV patients to a treatment regimen of either 25 mg of tenofovir alafenamide, (Gilead Sciences; n = 581) a prodrug of tenofovir, or 300 mg of Viread (tenofovir disoproxil fumarate, TDF; Gilead Sciences; n = 292) for 96 weeks. A quarter of patients were treatment-experienced, according to Chan’s presentation.

After completion of those 96 weeks, patients received open-label tenofovir alafenamide for 48 weeks. The primary endpoint of the study was the number of patients with HBV DNA less than 29 IU/ml by 48 weeks, to determine whether or not the efficacy of tenofovir alafenamide was non-inferior compared with TDF.

Patients treated with tenofovir alafenamide had an overall 63.9% virologic response rate compared with 66.8% in patients treated with TDF. Treatment difference was –3.6%, Chan said.

More patients treated with tenofovir alafenamide reached normal alanine aminotransferase levels compared with patients treated with TDF. In addition, patients who received tenofovir alafenamide also experienced less decline in hip and spine bone mineral density, and a smaller increase in serum creatinine compared with patients treated with TDF.

Rates of discontinuations (n = 30 for tenofovir alafenamide, n = 14 for TDF) due to treatment were comparable between the patient groups. Serious adverse events were also similar.

“In the resistance analysis at 48 weeks, no sequence changes were significantly different and no resistance was detected in either group,” Chan said.

Chan concluded: “Tenofovir alafenamide was safe and well-tolerated in hepatitis B e antigen-positive patients. Safety was improved, with less change in bone and renal parameters.”

In a press release from EASL, Tom Hemming-Karlsen, MD, PhD, EASL vice-secretary, said, “While tenofovir disoproxil fumarate is an effective treatment option for patients with chronic hepatitis B, we are pleased that this treatment … could provide patients with an equally effective, and yet safer, treatment option.” – by Melinda Stevens

Reference:

Chan HLY, et al. Abstract GS12. Presented at: International Liver Congress; April 13-17, 2016; Barcelona.

Disclosure: Chan reports serving as a consultant and lecturer for Gilead Sciences. Please see the full abstract for a list of all other authors’ relevant financial disclosures.

StephenW

替诺福韦alafenamide表现出相似的疗效，安全性的Viread在HBV
2016年4月15日

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巴塞罗纳 - 替诺福韦alafenamide是安全和乙肝e抗原阳性的患者显示非劣效率Viread的，根据国际在肝病会议一般的会议上提出3期研究结果。
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    长期疗效，富马酸替诺福韦酯的安全性...
    乙肝药物正在审查EMA营销中的应用

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    从2015年DDW亮点

“如果病人要长期治疗，我认为[替诺福韦alafenamide]是更好的选择，”亨利·L-Ÿ灿，医学博士，香港中国大学在中国消化疾病研究所所长，他的演讲时说。

亨利·L-Ÿ陈医师

亨利·L-ÿ赞

成龙和他的同事分配873乙型肝炎e抗原（HBeAg）阳性的慢性HBV患者的为25毫克的替诺福韦alafenamide的治疗方案（Gilead Sciences公司; N = 581），替诺福韦的前体药物，或300毫克的Viread的（替诺福韦富马酸，TDF; Gilead Sciences公司; N = 292）96周。四分之一的患者按照成龙的演讲是治疗经验。

那些96周完成后，患者接受开放标签泰诺福韦alafenamide 48周。该研究的主要终点是患者的HBV DNA小于29国际单位/毫升48周，数，以确定与TDF相比替诺福韦alafenamide的功效是否不劣。

在与TDF治疗的患者为66.8％相比，替诺福韦alafenamide治疗的患者有一个整体的63.9％病毒学应答率。治疗差异是-3.6％，成龙说。

替诺福韦治疗alafenamide更多的患者用TDF治疗的患者相比，达到正常谷丙转氨酶水平。此外，谁收到替诺福韦alafenamide患者也经历了髋部和脊柱骨密度下降较少，并与TDF治疗的患者相比，血肌酐升幅收窄。

由于治疗停药（30例替诺福韦alafenamide，N = 14 TDF）率分别病人群体之间的可比性。严重不良反应也相似。

“在48周的耐药性分析，没有顺序的变化是显著不同，在任一组未检测出抵抗，”Chan说。

陈总结说：“替诺福韦alafenamide是安全和乙肝e抗原阳性的患者耐受性良好。安全性进行了改进，在骨和肾功能参数变化较小。“

在从EASL，汤姆卷边卡尔森博士一份新闻稿中，EASL副书记说，“虽然富马酸替诺福韦酯是治疗慢性乙肝的有效治疗方案，我们很高兴，这种治疗......可提供患者用同样有效，但更安全，治疗选项“ - 由梅林达史蒂文斯

参考：

陈HLY，等。摘要GS12。发表在：国际肝病会议; 4月13日至17日，2016年;巴塞罗那。

披露：陈报告作为顾问和讲师Gilead Sciences公司。请参阅完整的抽象的所有其他作者的相关财务信息披露的名单。

齐欢畅2

taf确实不错。