简单汇总：LENVIMA+KEYTRUDA Combo

昨天推送不小心发错了，给大家带来的不便深表歉意。

Source : Eisai Co., Ltd. ADR (ESALY) Q1 2018 Results - Earnings Call Transcript

友情提示：

1）数据基本在ASCO等会上已披露，本期简单汇总；

2）数据虽好，可别忘了单臂试验，样本亦少。

  • 今年3月份乐伐替尼（也就是LEVIMA）在泥轰获批一线治疗肝癌，过去的四个月一直很注重推广的干活（promotional activities，鬼子的语法真是一如既往的统一）。通过药代和KOL会议等活动，最终让合适的病人用上LENVIMA。

    On oncology business, I would like to make report mainly focusing on LENVIMA and also Japan. Last March in the hepatocellular carcinoma, in Japan, we obtained approval of the first approval in the world and in the past four months, we have focused on promotional activities. That is in order to have LENVIMA preferred to appropriate patients through medical rep activities and through KOL seminars we are thoroughly disseminated this information.

  • 早些的结果来看，我们收到高度的回应，不仅仅疾病进展的病人，还包括那些难治患者，就像经历TACE的，部分患者也没有应答，现在这些患者也可以开LENVIMA了，过去四个月大概2800名患者开了LENVIMA的处方，其中一线治疗的处方是我们内部计划2倍以上(223%)。整个收入是之前预计的192%。

    As a result from early on, we have received high response not only for progressive disease patients but case refractive（感觉此处应为 refractory） patients in early stage are also being indicated. TACE is transcatheter arterial chemoembolization, even despite multiple TACE, some patients did not respond and even those patients are now indicated for and in the past four months about 2,800 patients were prescribed with LENVIMA and especially as the first line prescription is increasing at a pace that is twice as much as our internal plan. And revenue is 92% above the plan. And Japan is showing 2.9 times as much growth as the previous year.

  • 在全球多中心三期临床REFLECT研究中，日本亚组的ORR 46.9% ，而多个真实世界的研究ORR 40-46%与之接近，并被写进实际的临床指南，这也是10年来首个获批治疗HCC的一线药物。患者的AFP等指标下降，有动力治疗，这是我们收到的反馈。我们即将创造肝癌治疗领域的革命性改变。

    On July 14, at HCC-related study session, there was a report of use of LENVIMA in more than 10 patients. And our arm was very high of 40% to 46%. This is Phase III REFLECT study. And from that study, Japanese population is selected and 46.9% was ORR in Japanese population and that result is produced in clinical practice - in actual clinical practice. This is the first first-line hepatocellular carcinoma in about 10 years. Patients reviewed the images together with their physicians and they see too much shrinkage. And alpha-site protein（估计是 alpha-fetoprotein） marker, two more markers by reducing dramatically and patients themselves feel stronger motivation in their treatment. That is the feedback that we are receiving. We are about to bring about revolutionary change in hepatocellular carcinoma treatment.

  • 下面是LEVIMA和KEYTRUDA的联合用药的数据，目前是四种肿瘤的适应症，瀑布图可以看出在这些肿瘤中联合用药有着很好的抗肿瘤潜力。首先看子宫内膜癌EC（注：8月2日获得FDA的BTD，RCC之后的第二个BTD），这里不考虑PD-L1表达及MSI状态，我们可以看到很强的抗肿瘤活性。

    I would like to discuss clinical data on LENVIMA/KEYTRUDA combination. This slide shows four different cancer types. This is a waterfall plot of combination of LENVIMA/KEYTRUDA. As I review this slide together with you, I'm struck that across cancer types this combination therapy has potent anti-tumor effect. To discuss in more detail, regarding endometrial carcinoma first, irrespective of PD-L1 status and irrespective of microsatellite instability, strong anti-tumor effect is observed.

  • RCC中也不考虑先前治疗历史及PD-L1表达也都可以观察到响应。头颈癌中也观察到普遍的抗肿瘤效果：至于部分患者中发现的HPV感染这个标志物，在这里，大多数患者是否应答与是否感染HPV也是没有关系的。最后是肝癌，我们知道疾病的背景很复杂，有HBV、HCV或是酒精相关，抗肿瘤的效果和这些因素也是不相关的。

    In renal cell carcinoma, irrespective of prior therapy history and irrespective of PD-L1 status, broadly tumor shrinkage effect is observed in head and neck cancer. One of the carcinogen background factor is reported to be human papillomavirus. Irrespective of viral infection status in most of the patients, tumors shrinkage was confirmed. Lastly, hepatocellular carcinoma, disease background of this carcinoma is very complex and hepatitis B, hepatitis C virus and alcoholic backgrounds; irrespective of these factors, a very strong tumor shrinkage effect was observed.

  • How to interpret this data, first, indication population with a combination we may be able to expand indication by a large margin. That possibility is suggested. As one example of that, the other day regarding endometrial carcinoma, FDA gave designation of research therapy, we reported on that earlier and this breakthrough therapy designation is also given for renal cell carcinoma. And LENVIMA combination therapy was also earlier given this designation for renal cell carcinoma.

  • combo的后期临床研究将会继续进行，将会继续和默克合作。相比任何一个单药，联合都体现出不错的临床效果，这种看起来是一个协同增强的效果而不是简单的相加，我将会详细介绍。首先看EC，研究者评估的ORR和PFS分别39.6%和7.4个月，相比两个单药的数据（非头对头）：LENVIMA的21.8%和5.4个月、KEYTRUDA的13.0%和1.8个月，都有很明显的提升，而且也好于简单的数字相加。

    So, LENVIMA/KEYTRUDA combination late stage development will be pursued continuously and we would like to continue to make contribution to patients together with Merck. LENVIMA/KEYTRUDA combination is compared against monotherapy of each drug according to reported data so far. The message is very simple; the combination has clinical effects, so that is above the monotherapy. And this effect seems to be synergistic effect not additive effect. I would like to address each cancer type in more detail. First endometrial carcinoma, objective response rate and PFS progression-free survival data are data that I would like to call your attention to, ORR is close to 40% for the combination therapy and PFS median is 7.4 months in comparison to reported data for each monotherapy, they are higher and it is better than addictive result.

  • RCC中联合组的ORR 、DCR和PFS也发现这种协同增强，独立的影响评估ORR和PFS分别66.7%和18个月，好于两个单独的数据；LENVIMA单药的二线数据分别27%和7.4个月，而KEYTRUDA的单药一线分别38.2%和8.7个月，另外也好于nivo+ipi双免疫联合的数据：42%和11.6个月（笔者：鸡冻之余再冷静下，这只是30人的小临床）。

    The synergistic effect is suggested for RCC, ORR and PFS are shown.Regarding ORR, it's about 70% 18 months PFS. And these are better than each monotherapy and better than additive results. And disease control rate is more than 90%. In all of these measurements, ORR, DCR, PFS - these are the results we have and in comparison to nivolumab and ipilimumab, for all of these items we have shown a better result and approval was received earlier in the United States.

  • 再来看头颈癌的2线以上联合，ORR和PFS分别40.9%和8.2个月，没有LENVIMA治疗头颈癌的数据，相比KEYTRUDA20%以内的ORR和2个月出头的PFS，提升十分明显。

    Regarding head or neck cancer, the second-line therapy or in later therapy, data was obtained but we did not have such data for LENVIMA monotherapy, so here keynote data for KEYTRUDA is shown, ORR for combination is 40%, PFS is eight months. Regarding KEYTRUDA monotherapy in comparison to recorded data it is twice as much or four times as much remarkable clinical results in fact are shown.

  • 最后看肝癌一线的联合治疗，研究者角度评估的ORR和PFS分别42.3%和9.69个月，相比LENVIMA单药一线数据：24.2%和7.4个月 和 KEYTRUDA二线单药17%和4.9个月 有了明显的超越，另外联合组疾病进展/PD率为0，二单药组分别15%和33%。

    Lastly, as for hepatocellular carcinoma, ORR is 40% or above them progression free survival is 9.7 months. LENVIMA alone or KEYTRUDA alone results are exceeded by a combination therapy. Earlier stage in this study, so we do not have definitive results yet, but best response and progressive disease, patient that was determined to be progressive disease but zero in combination therapy and this is a remarkable in comparison to monotherapy. In almost all patients, there was no PD. So in that sense, not additive but synergistic effect is suggested.

  • In these four cancer types, we will continue with our development and accelerate development, and together with Merck, we will pursue late stage development. For other cancer types, we would also like to develop and at the earliest possible stage would like to report the outcome to you.

这段主要是EISAI的肿瘤线布局，也没啥好讲，紧密团结在以LENVIMA为核心的pipeline周围，高举联合KEYTRUDA的旗帜不动摇。

  • In oncology area, this is the pipeline that we have. We have these key words as the basis for the pipeline. First is tumor micro environment, there are two major platforms related to tumor microenvironment. First is, as Mr. Owa explained, LENVIMA and PD-1 antibody combination. TKI and PD-1 antibiotic combination is showing synergistic effect and the mechanism is now being elucidated. And in this area, we believe that we are the front runner in the world and that is requested in the pipeline. Second platform is halaven Eribulin or Halichondrin platform. Using that platform, we have these two themes, MORAb-202, which is an ADC and Halichondrin deliberative.

  • These are being developed. And the second keyword is cancer evolution. Cancer cell genetic mutations will change over time and will be changed other result of radiotherapy and pharmacotherapy. To approach this cancer evolution, targeting hormone positive breast cancer, we have ESR-1 inhibitor in the pipeline and those that act on [indiscernible] factor. Thirdly, they key word is precision medicine which is an approach against cancer driver gene, FGFR4, FGFR1, FGFR2, FGFR3, EZH2; these are targeted in the development. Depending on the assets, we may continue to encourage develop or depending on the assets we may partner with the best partner and through these approaches we would like to continue to make efforts to cure cancer.

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