2014年12月22日讯/生物谷BIOON/--正当罗氏还沉浸在 Kadcyla和Perjeta（帕妥珠单抗）获得治疗乳腺癌的特许经营权，并对其抱有极大期待之际，近日一盆冷水浇下，遭遇了严重挫折。后期研究发现，这两种新药的疗效无法战胜赫赛汀和化疗，让罗氏扩大新药市场的计划遭遇滑铁卢，并且股票也有所下降。
罗氏在1095名未接受前期治疗的HER-2阳性乳腺癌患者中验证Kadcyla和Perjeta相对于赫赛汀的疗效。试验组分为Kadcyla加Perjeta、Kadcyla、赫赛汀加化疗三组。结果证明这三种治疗方案都能延长患者的存活期，并且无一患者病情恶化。但是无论是Kadcyla单独用药还是Kadcyla加Perjeta联合用药都无法击败赫赛汀加化疗的疗效。
罗氏的发言人Ulrike Engels-Lange对媒体表示，罗氏曾希望这两种新药能在不依靠传统化疗的情况下延长患者的无进展生存期，尽管试验证明没有达到这一预期，但是在获批的适应症和对HER-2阳性晚期乳腺癌患者的用药上，试验都未能颠覆之前的结果。
然而，这样的试验结果对罗氏而言不是好兆头。罗氏正在准备与赫赛汀竞争的生物仿制药，并且希望加强肿瘤药方面的投资组合。赫赛汀是罗氏今年前九个月销售量第三大的药物，销量达到了惊人的47亿瑞士法郎（48亿美元）。悲剧的是，上周赫赛汀的第一个仿制药在印度上市了，在欧洲的专利期也于7月份到期，在美国的专利权还会持续到2019年。因此罗氏必须赶在其他仿制药上市之前制造出自己的赫赛汀仿制药，以抢占市场先机。
Kadcyla本来是有望成为取代赫赛汀成为新一代治疗乳腺癌的强效药物，据说可以将赫赛汀的活性成分直接传递到癌细胞，这一新突破曾引起了医生和相关评论家的重大反响。Kadcyla于2013年获批，也算是众望所归，并且早期的销量也验证了这一点。Perjeta和Kadcyla销量惊人，在2014年最初的9个月中分别达到了6.33亿法郎和3.71亿法郎的好成绩。
Perjeta也是受到无数关注的宠儿，并且完成了今年第一波获批新药的目标。作为赫赛汀附加使用的新药，Perjeta使患者的生存期超过了15个月。
然而，最近的数据却使得Kadcyla蒙受了巨大的阴影。有分析者预测，Kadcyla的销量会大大下跌，还有预测认为到2017-20年，Kadcyla的每股预期收益会下降5%。
与此同时，罗氏还面临着付款人的压力。八月份，英国的成本效益监管机构—— 英国国家卫生医疗质量标准署宣布，Kadcyla的售价太高，保险很难承受。尽管罗氏承诺给出折扣，然而14.5个月疗程花费的90831英镑（142000美元）已经超出NICE规定的肿瘤药售价范围。
然而，罗氏在给投资者的报告中宣称，还有一线曙光。Kadcyla已经快要成为治疗乳腺癌的二线药物，而Perjeta也获得了开创性的术前批准。
罗氏认为，乍看之下此次试验结果会给公司带来负面影响，然而实际的影响并不如想象的那样大。究竟罗氏能否渡过此次难关，还要看往后的试验和营销结果。
原文 Roche's bid to sub Kadcyla for Herceptin takes a big hit with lackluster PhIII data
Roche ($RHHBY) has been riding high on the success of its newly augmented breast cancer franchise， charting promising numbers for standout drugs Kadcyla and Perjeta. But the company faced a stinging setback Friday. The next-gen duo failed to beat Herceptin and chemo in a late-stage study， putting a damper on Roche's plan to expand the market for its new drugs and sending its shares in a downward spiral.
Roche's Marianne study tested the two drugs against Herceptin in 1，095 previously untreated patients with advanced HER2-positive breast cancer. Kadcyla plus Perjeta， Kadcyla on its own， and Herceptin--the company's gold-standard therapy--plus chemotherapy all three helped people live longer without their disease worsening. But neither Kadcyla by itself nor the Kadcyla/Perjeta combo beat Herceptin and chemo， Roche said in a statement.
The company had hoped to show its new drugs could improve progression-free survival in untreated patients， without traditional chemotherapy， Ulrike Engels-Lange， Roche spokeswoman， told FiercePharma in an email. "While Marianne didn't achieve this， these results do not impact either the approved indications or use of Kadcyla or Perjeta in HER2-positive [advanced breast cancer]，" she said. "We are proud that our medicines Perjeta and Kadcyla in their approved indications have helped people with HER2-positive [breast cancer] live longer."
The news does not bode well for Roche as it prepares for biosimilar competition to Herceptin and ramps up its cancer portfolio to take up the slack. Herceptin was Roche's third-biggest drug in the first nine months of this year， with eye-popping revenue of 4.7 billion Swiss francs ($4.8 billion). But Herceptin's first biosimilar hit the Indian market last week， and its main patent on the product expired in Europe in July. The U.S. patent runs through 2019.
Kadcyla was supposed to handle all of that. The "armed antibody" delivers Herceptin's active ingredient directly to cancer cells， a breakthrough approach that excited doctors and analysts alike. Its approval in 2013 was among the most anticipated in years， and early sales results justified that hope. Perjeta and Kadcyla have chalked up impressive numbers， with sales of 633 million francs and 371 million francs， respectively， for the first 9 months of 2014.
Perjeta has been watched closely， too， and it hit a big goal with first-line approval earlier this year. As an add-on to Herceptin， Perjeta helped patients live more than 15 months longer， according to a study presented in September， an unprecedented result in HER2-positive cancer.
But Kadcyla's time in the sun could wane in light of the troubling study data. Analysts' sales estimates for Kadcyla "will have to come down significantly，" Fabian Wenner， an analyst at Kepler Cheuvreux in Zurich， said in a report， and Bernstein's Tim Anderson predicted earnings per share forecasts for the 2017-20 period would fall by around 5%.
Roche is also facing payer pushback for Kadcyla. In August， the U.K.'s cost-effectiveness watchdog， the National Institute for Health and Care Excellence (NICE) declared that the company's heralded breast cancer treatment was too expensive to cover. Roche proposed a discount to its list price， but Kadcyla costs ￡90，831 ($142，000) for a 14.5 month course of treatment， leaving it well above the cost-effectiveness threshold for cancer drugs， NICE CEO Andrew Dillon said at the time.
Still， there could be some light at the end of the tunnel for Roche， Anderson said in a note to investors. Kadcyla is already charting growth as a second-line breast cancer treatment， and Perjeta has that groundbreaking before-surgery approval.
"At first blush， this sounds disastrous for Roche given the importance of the HER2+ breast cancer franchise， but in reality the EPS impact is less negative than might be expected， at least by our preliminary assessment，" Anderson said.