Gilead Begins Single Pill Hepatitis C Study for 2014 Approval

StephenW

Gilead Begins Single Pill Hepatitis C Study for 2014 ApprovalBloomberg, By  Michelle Fay Cortez and Ryan Flinn on July 27, 2012



Gilead Sciences Inc. (GILD) (GILD) said it plansto start a combination study of two drugs in a single pill totreat hepatitis C by the end of the year, putting it on track torequest U.S. regulatory approval for the medicine in 2014.
Gilead, which spent $10.8 billion to acquire one of themedicines, GS-7977, plans to combine it with another, GS-5855,in a trial of 800 patients starting in the fourth-quarter, saidNorbert Bischofberger, chief medical officer of the Foster City,California-based company, in a conference call yesterday. If thecombination is effective, the company could apply for regulatoryapproval in the middle of 2014, Bischofberger said.
Gilead is among several drugmakers racing to develop newhepatitis C treatments that act more quickly with fewer sideeffects than the current standard of care. The goal is toprovide doctors and patients with simpler, more effectivetreatments, Bischofberger said.
The company aims for a therapy that “will clearly be a onepill, once daily, maybe a 12 week course,” for patients withall different types of hepatitis C, Bischofberger said. “That’sour goal. We are very close.”
Conventional therapy combines ribavirin with interferon, aninjected immune-boosting protein that can cause flu-like sideeffects, for as long as 48 weeks.
Gilead is competing with Abbott Laboratories, Bristol-MyersSquibb Co., Johnson & Johnson, Merck & Co. and VertexPharmaceuticals Inc. (VRTX) (VRTX) to develop a new generation of hepatitis Ctreatments. Rising deaths among baby boomers from hepatitis Cprompted U.S. health officials to declare in May that the entireage group is at risk and should be tested for the disease.
Previous Studies Another study of GS-7977, given with ribavirin, found nineof nine patients who were previously untreated had a sustainedresponse to the drug, with no signs of virus in their bodiesafter finishing the therapy. A second study, however, found just53 percent of patients had a similar benefit, a difference thecompany is still trying to figure out, Bischofberger said.
Gilead, the world’s biggest maker of AIDS drugs, yesterdayreported net income fell (GILD) 4.6 percent in the second quarter to$711.6 million, or 91 cents a share, from $746 million, or 93cents, a year earlier. Earnings, excluding one-time items, of 99cents a share beat the 95 cents a share average of 25 analystestimates compiled by Bloomberg. Revenue jumped 13 percent to$2.41 billion, the company said in a statement yesterday.
Gilead shares rose (GILD) 2.6 percent to $53 at 5:46 p.m. in NewYork, after closing yesterday up less than 1 percent at $51.68.The stock has gained 23 percent in the past 12 months.
Gilead press release:


    In April, Gilead announced interim data from the Phase 2 ATOMIC study       examining a 12-week course of treatment with the investigational       once-daily nucleotide GS-7977 plus pegylated interferon and ribavirin       (RBV) in treatment-naive patients with genotype 1 chronic hepatitis C       virus (HCV) infection. The study found that 90 percent of patients       achieved a 12-week sustained virologic response (SVR12), defined as       maintaining undetectable viral load 12 weeks after the completion of       therapy. These findings were presented at the 47th Annual       Meeting of the European Association for the Study of the Liver (EASL) in       Barcelona, Spain.                                
Also in April, Gilead announced interim data from the Phase 2 ELECTRON       study examining GS-7977 plus RBV in treatment-naive patients with       genotype 1 chronic HCV infection. Of the 25 patients who completed 12       weeks of treatment, 88 percent achieved a four-week sustained virologic       response (SVR4). Three patients experienced viral relapse. These       findings were presented at EASL.                                
Lastly in April, Gilead announced interim results from the Phase 2       QUANTUM study examining a 12-week duration of GS-7977 plus RBV in       treatment-naive patients. Twenty-five patients were randomized to the       12-week treatment arm: 19 genotype 1 patients; four genotype 3 patients;       and two genotype 2 patients. At the four-week post-treatment time       period, data were available for 17 genotype 1 patients. Of these, 59       percent achieved SVR4 and 41 percent experienced viral relapse.       Additionally, seven of the patients who reached the eight-week       post-treatment time period, and who achieved SVR4, remained HCV RNA       undetectable.                                   


Gilead issued earnings yesterday, from Gilead conference call:
Norbert W. Bischofberger
My remaining comments will focus on hepatitis C, where progress has been rapid.
At the EASL conference earlier this year, data were disclosed from 2 Phase II studies of a 12-week, 12-week course of GS-7977 and Ribavirin in genotype 1 infected treatment-naïve patients. In the ELECTRON study, the SVR4 rate in genotype 1 naïve patients was 88% or 22 out of 25 patients and in the QUANTUM study, the SVR4 rate in genotype 1 treatment-naïve patients was 53% or 10 out of 19 patients.
I would now like to provide an update on new data from 2 Phase II studies evaluating 24 weeks of treatment with GS-7977 and Ribavirin, in treatment-naïve genotype 1 infected patients.
In the QUANTUM study, 19 genotype 1 patients were randomized to receive 24 weeks of GS-977 and Ribavirin. Of those 19 patients, 10 were 53% achieved in SVR4.
The second trial is conducted by the NIAID, in a cohort of genotype 1 infected predominantly African-American patients, a population which has historically been more difficult to treat.
In that study, of the first 9 patients who completed 24 weeks of treatment with GS-7977 and Ribavirin all 9 or 100% achieved SVR4.
These results from the QUANTUM and the NIAID studies are included in Slides 31 and 32 of earnings slide deck.
In summary, in the various Phase II cohorts, treatment with GS-7977 and ribavirin for 12 or 24 weeks was in genotype 1 infected patients, resulted in SVR4 rates between 53% and 100%.
In May and June of this year, discussions were held with the U.S. FDA and 3 European regulatory agencies, and agreement has been achieved on a comprehensive Phase III development plan for GS-7977 and on a Phase III plan for GS-7977 in combination with the NS5A inhibitor, GS-5885.
The initial NDA and MAA filings will be for GS-7977 and will include data from 4 Phase III studies, 3 conducted in genotype 2/3 infected patients and 1 in genotype 1 infected patients.
The 3 genotype 2/3 studies are FISSION, POSITRON and FUSION. FISSION is the first study in 500 genotype 2/3 naïve patients, comparing 12 weeks of treatment with GS-7977 and Ribavirin to the current standard of care of 24 weeks of treatment with peg-interferon Ribavirin.
The second study, POSITRON, is comparing 12 weeks of treatment with GS-7977 and Ribavirin in 240 genotype 2/3 interferon intolerant or ineligible patients to placebo.
And thirdly, FUSION is a study in 200 genotype 2/3 treatment experienced patients exploring 12 or 16 weeks duration of treatment with GS-7977 and Ribavirin.
And all 3 trials, FISSION, POSITRON and FUSION are now fully enrolled. And the last patient in these studies has started dosing just today.
A fourth Phase III study called NEUTRINO is a single arm study evaluating a 12-week course of GS-7977, peg-interferon and Ribavirin in 300 genotype 1, 4, 5 and 6 infected patients.
Screening in the NEUTRINO study is completed and the last patient should start dosing by mid-August.
This same regimen, 12 weeks of GS-7977, peg-interferon, ribavirin, was evaluated previously in genotype 1 patients in a Phase II study, called ATOMIC and resulted in SVR4 rate of 92%.
These Phase IV, Phase III studies are outlined on Slides 33 and 34 in our earnings slide deck.
With these 4 Phase III studies underway, we anticipate being able to file for regulatory approvals for GS-7977 by the middle of next year.
If successful, the initial indication will for 12 to 16 weeks of treatment with GS-7977 and Ribavirin in genotype 2/3 infected patients, and for 12 weeks of treatment with GS-7977, peg-interferon and Ribavirin in genotype 1, 4, 5 and 6 infected patients.
In PEMARON [ph], we're also advancing GS-7977 in combination with GS-5885 for the treatment of genotype 1 infected patients.
GS-7977 and GS-5885 were successfully co-formulated into a single pill, fixed dose combination. The IND on this fixed dose combination was filed a month ago and the Phase I study evaluating the bioavailability was initiated last week.
If the Phase I data show that the fixed dose combination results in adequate exposures of GS-7977 and GS-5885, we expect to initiate the Phase III study with this fixed dose combination in the fourth quarter of this year.
This Phase III study is planned as a forearm randomized trial in 800 patients, evaluating the fixed dose combination with or without Ribavirin for either 12 or 24 weeks in treatment-naïve genotype 1 infected patients.
The study will contain an interim futility analysis after the first 200 patients or 50 per arm have been enrolled, an independent data, safety monitoring board will evaluate the SVR4 rates of the 12-week treatment arms.
If the predefined response rates are met, then the remaining 600 patients will be subsequently enrolled.
At the time of this interim analysis, additional data will be available from the ELECTRON study on 12 weeks of treatment with GS-7977 and GS-5885 and Ribavirin in genotype 1 null responders and genotype 1 naïve cohorts, as well as 12-week data from the ongoing BMS study of GS-7977 and Daclatasvir with or without Ribavirin.
All these data will allow us to decide on the design of the second confirmatory study supporting the filing of GS-7977, 5885 fixed dose combination.
If treatment of genotype 1 infected patients with the fixed dose combination GS-7977, 5885 for 12 weeks, results in acceptable high SVR4 rates, then the second confirmatory study could be initiated in the first half of 2013.
The fixed dose combination regulatory filings could, in that case, follow the initial GS-7977 filings a year later by mid-2014.
The development strategy for the GS-7977, GS-5885 fixed dose combination is outlined in Slide 36 of our slide deck.
In summary, a number of programs had been advanced across therapeutic areas. GS-7340 co-formulated in 2 single tablet regimens is advancing in Phase II. GS-1101 is advancing in Phase III and notably, 4 Phase III studies evaluating GS-7977 in genotype 1 through 6 HCV infected patients are fully enrolled and the NDA, MAA are on track to be filed by the middle of next year.
Finally, we plan to advance the fixed dose combination of GS-7977 and 5885, currently in Phase I clinical testing, into Phase III in the fourth quarter of this year.

StephenW

Gilead公司于2014年批准开始单一的药片丙型肝炎的研究
彭博，7月27日，2012年由米歇尔·费伊科尔特斯和Ryan弗林

Gilead Sciences公司（GILD）（GILD）表示，它计划在一个单一的药丸治疗丙型肝炎年底开始了这两种药物的组合研究，把轨道上，它要求在2014年美国监管部门批准的药。

基列，其中花了108亿美元，以获得1的药品，GS-7977，计划要结合另外，GS-5855，800在第四季度开始，患者的试验中，，说：诺伯特Bischofberger，行政的医疗人员福斯特城，加利福尼亚州的公司在一个电话会议，昨天。如果组合是有效的，公司可以申请在2014年中期监管部门的批准，Bischofberger说。

Gilead公司是其中一些制药公司竞相开发新的丙型肝炎的治疗，更迅速地行动与副作用较少，比现行标准的护理。我们的目标是为客户提供更简单，更有效的治疗方法，医生和病人，Bischofberger说。

该公司旨在为说：“显然是一​​丸，每日一次，也许是12周的课程”，为所有不同类型的丙型肝炎患者的治疗，Bischofberger说。 “这是我们的目标。我们都非常接近。“

常规疗法相结合利巴韦林与干扰素，注射免疫增强蛋白可引起类似流感的副作用，长达48周。

Gilead公司与雅培制药，施贵宝公司，强生公司，默克制药公司和Vertex制药公司（VRTX）（VRTX）竞争，开发出新一代丙型肝炎治疗。丙型肝炎的婴儿潮一代中上升的死亡，促使美国卫生官员在5月宣布，整个年龄组是在风险和疾病应测试。
以往的研究

GS-7977的另一个研究，与利巴韦林给予的，发现九谁是以前未经治疗的患者中有9人在他们的身体没有任何病毒的迹象持续反应的药物，完成治疗后。然而，另一项研究发现，只有53％的患者有类似的好处，该公司仍在试图找出差异，Bischofberger说。

Gilead公司，是世界上最大的艾滋病药物生产商，昨日报道，净收入下跌（GILD）在第二季度的4.6％，从去年同期的7.46亿美元，或93美分，至711.6亿美元，或每股91美分，。收入，扣除一次性项目，每股盈利99美分，比估计的25分析师的平均每股95美分，彭博汇编。收入增长13％至2.41亿美元，该公司昨天在一份声明中说。

Gilead的股票上涨在下午5时46分在纽约（GILD）的2.6％，至53美元，收盘上涨不到1％昨天51.68美元，后。该公司股价已经上涨了23％，在过去12个月。
Gilead的新闻发布：

    今年四月，Gilead公司宣布从第二阶段的原子研究的中期数据，检查每日一次的调查核苷酸GS-7977加聚乙二醇干扰素和病毒唑（利巴韦林）治疗过的患者1型慢性丙型肝炎的治疗12周的课程肝炎病毒（HCV）感染。研究发现，90％的患者取得了为期12周的持续病毒学应答（SVR12），保持在治疗结束12周后检测不到病毒载量的定义。这些研究结果发表在肝脏研究欧洲协会第47届年会在西班牙巴塞罗那（EASL）。

此外，在今年4月，Gilead公司宣布从第二阶段的电子研究的中期审查GS-7977加利巴韦林治疗基因1型慢性丙型肝炎病毒感染的初治患者的数据。 88％的25例完成12周的治疗，取得了四个星期的持续病毒学反应（SVR 4）。三名患者出现病毒复发。这些研究结果发表在欧洲肝病学会。

最后在今年4月，Gilead公司宣布中期业绩从第2阶段的量子化学研究，在治疗过的患者检查GS-7977加利巴韦林12周时间。二十五名患者被随机分配到12个星期的治疗组：19型1例;四个基因型3例;两个基因型2例。在四个星期的治疗后一段时间，数据为17型1例。其中，59％实现了SVR4和41％的病毒复发。此外，7个病人，谁达到了八周的治疗后的一段时间，取得的SVR4仍然丙型肝炎病毒RNA检测不到。

Gilead公司昨天发出盈利，从基列电话会议：
诺伯特·W·Bischofberger

我剩下的意见，将侧重于C型肝炎，进展迅速。

在今年早些时候，欧洲肝病学会会议，从2第二阶段研究为期12周，12周课程的GS-7977和利巴韦林基因型1感染治疗初治患者的数据进行了披露。在电子学习，在1型初治患者的SVR4率为88％或22 25例，在量子化学研究，在1型治疗初治患者的SVR4率为53％或10 19例。

现在我想天真治疗基因1型感染患者，2第二阶段评估与GS-7977和利巴韦林治疗24周的研究提供新的数据更新。

在量子化学研究，19基因型1病人随机接受GS-977和利巴韦林24周。这19例患者中，有10人在SVR4达到53％。

二审由NIAID的进行，在1型感染主要是非洲裔患者，历来更难以治疗的人口世代。

在这项研究中，所有9或100％，完成了与GS-7977和利巴韦林治疗24周的第9例取得的SVR4。

从量子和NIAID的研究，这些结果包括在盈利幻灯片幻灯片31和32。

总之，在各种二期同伙，GS-7977和利巴韦林治疗12周或24周是1型感染患者中，导致在SVR4率在53％和100％之间。

今年五月和六月举行，讨论了美国FDA和3个欧洲监管机构，并已取得了全面的GS-7977第三阶段的发展计划和第三阶段计划的协议，结合GS-7977 NS5A的抑制剂，GS-5885。

初始NDA和MAA申请将GS-7977，将包括数据从4三期研究，基因型2/3的感染患者进行3和1基因型1感染的病人。

3基因型2/3的研究是裂变，正电子和融合。裂变是500基因型天真的2/3的病人在第一项研究，比较，GS-7977和利巴韦林治疗12周的照顾与PEG-干扰素利巴韦林治疗24周的现行标准。

第二项研究中，正电子，在240基因型2/3干扰素不能耐受或不合格的患者服用安慰剂比较，GS-7977和利巴韦林治疗12周。

第三，融合是一个在200基因型的研究探索12或16周与GS-7977和利巴韦林治疗时间2/3治疗经验的患者。

和3个试验中，裂变，正电子和融合，现在完全登记。计量就在今天已经开始，并在这些研究中的最后病人。

第三第四个阶段的研究，被称为中微子是单臂研究，评估在300基因型1，4，5和6感染患者的GS-7977，PEG-干扰素和利巴韦林12周的课程。

在中微子研究筛选完成后，最后病人应该8月中旬开始给药。

此相同的方案，12周GS-7977，PEG-干扰素，病毒唑，以前在基因1型患者在第二阶段的研究进行了评估，被称为ATOMIC和92％，导致在SVR4率。

这些四期，三期研究概述在我们的盈利幻灯片幻灯片33和34。

我们与这4个第三阶段研究正在进行中，预计明年年中能够为GS-7977的监管部门的批准文件。

如果成功的话，最初的指示将12至16周的治疗与GS-7977和利巴韦林基因型感染患者的2/3，为12周的治疗，GS-7977，PEG-干扰素和利巴韦林基因型1，4， 5日和6感染的病人。

在PEMARON [PH]，我们也推进GS-5885 GS-7977 1型感染患者的治疗组合。

GS-7977 GS-5885进行了成功合作，制定成一个单一的药片，固定剂量组合。这种固定剂量组合实业是一个月前提交上周开始第一阶段的研究，评估生物利用度。

如果第一阶段的数据表明，充分暴露GS-7977 GS-5885的固定剂量组合的结果，我们希望启动第三阶段研究这个固定剂量组合在今年第四季度。

这第三阶段的研究计划作为前臂800例患者的随机试验，评估为12或24周的治疗天真的基因型1感染者或无利巴韦林固定剂量组合。

这项研究将包含或每臂的前200名患者已招收50中期徒劳分析后，一个独立的数据安全监测委员会将评估12周的治疗武器的SVR4率。

如果预定义的响应率得到满足，那么剩下的600例患者将随后参加。

在本中期分析时，额外的数据将可从电子研究与GS-7977 GS-5885，在1型空应答和基因型1天真的同伙利巴韦林12周的治疗，以及12周的数据从正在进行BMS的GS-7977和利巴韦林或不Daclatasvir研究。

所有这些数据将让我们决定支持GS-7977，5885固定剂量组合申请的第二个验证研究设计。

如果治疗基因1型感染患者固定剂量组合GS-7977，12周，5885，在接受高的SVR4率的结果，然后第二验证研究可在2013年上半年开始。

在这种情况下，监管机构备案的固定剂量组合，可以按照最初的GS-7977申请一年后，由2014年中期。

的发展战略，为GS-7977 GS-5885固定剂量组合概述我们的幻灯片在幻灯片36。

总之，节目数量已提前跨越的治疗领域。 GS-7340单锭疗程共同制定推进第二阶段。 GS-1101第三阶段推进，值得注意的是，4第三阶段的研究在基因型1至6丙型肝炎病毒感染患者的GS-7977完全注册和轨道上的保密协议，备忘录是到明年年中提出的。

最后，我们打算提前GS-7977和5885的固定剂量组合，我目前在第一阶段的临床试验进入第三阶段，在今年第四季度。