2013年2月25日，辉瑞公司的抗癌药Xalkori（克唑替尼，crizotinib）获得中国国家食品药品监督管理局（SFDA）批准在中国上市，用于治疗通过SFDA批准的检测确认为间变性淋巴瘤激酶（ALK）阳性的局部晚期或转移性非小细胞肺癌（NSCLC）。
克唑替尼的临床试验在ALK融合基因生物标记检测呈阳性的肿瘤患者中进行，这样增强了治疗有效的可能性。这种方法首次应用在肺癌的治疗中，它可以使研究人员在特定的患者人群中观察到药物强劲的疗效。
两项共纳入255名ALK-阳性的NSCLC肿瘤患者的多中心的单组临床试验结果表明，，该药的治疗总有效率（ORR）分别为51%和61%。初步流行病学调查表明，NSCLC肿瘤患者中约3%~5%的患者为ALK-阳性，也就是说，全球每年大约有28000~46000名的ALK-阳性NSCLC患者。
克唑替尼在美国的审批过程仅仅用了四年时间，这包括从发现NSCLC肿瘤患者中有ALK融合基因到研发的该药获得美国FDA的批准时间总和，这是肿瘤学领域的一个伟大的成就，同时，它也证明了学术研究、制药、诊断和监管机构之间加强合作的重要性。
而克唑替尼在中国的审批程序，从提交新药申请到最近获得SFDA的批准也仅用了11个月，原因是中国将其列入了国家药品评价中心（CDE）的快速审批通道。
克唑替尼自从2011年8月获得美国FDA批准后，陆续在日本、韩国、欧盟等地获得认证机构的批准。在获得SFDA的批准后，克唑替尼预计将在今年年中正式在中国市场进行发售。
Pfizer announces SFDA approval for Xalkori, looks for more China partnerships
Published: 2/26/2013
United States-based firm Pfizer has received approval from China's State Food and Drug Administration (SFDA) for Xalkori (crizotinib) as a treatment for non-small-cell lung cancer (NSCLC) that is anaplastic lymphoma kinase (ALK)-positive, alongside use of an already approved diagnostic test, according to a press release from the firm issued yesterday (25 February).
Xalkori is described by Pfizer as the world's first personalised lung cancer therapy, and was granted approval in China through the Center for Drug eva luation (CDE)'s fast-track approval channel in a process lasting 11 months from New Drug Application (NDA) to SFDA clearance. The CDE in January issued a positive review of Xalkori, which stated that data from three Phase I, II, and III global trials (rather than trials held in China) were considered. The Phase II study included 234 Chinese patients, and there were 157 Asian patients and 29 Chinese patients in the Phase III study comparing Xalkori with pemetrexed or docetaxel. There was no efficacy or tolerability differences between Chinese and non-Chinese patients. The CDE requested that Pfizer continued its global Phase III and East Asia Phase III trial in order to assess overall survival data, as reported by PharmAsia News, and the CDE also worked with the US firm to establish a standard diagnostic test for ALK-positive NSCLC prior to the approval.
Separately, Pfizer's China country manager Wu Xiaobing has declared that the firm intends to develop further partnerships with local companies in China, speaking in an interview with The Wall Street Journal reported today (26 February). Wu states that Pfizer is open to alliances in research, manufacturing and marketing of drugs, and cites shrinking margins in the country due to government price-cutting policies, as well as the benefits gained from local knowledge of the drug registration process. "If we were alone, it would take such a long time to make our drugs accessible to patients," Wu said.
Outlook and implications
As elsewhere around the world, the approval of Xalkori in China is particularly notable for its speed: 11 months to approval is unprecedented, and signifies that the SFDA is taking steps to improve its notoriously laborious drug approval process to be more in line with international standards. Xalkori's development took just four years from first discovery to gaining initial US FDA approval in August 2011, and the drug is described by one of the principal innovators, Dr Jean Cui, as representing "a paradigm shift in NSCLC treatment… away from a one-size-fits-all approach to biomarker-based treatment", as quoted in the firm's press release (see United States: 29 August 2011: Pfizer's Personalised Late-Stage Cancer Drug Xalkori Receives FDA Approval). Analysts expect that it could generate USD2.5 billion in sales globally, despite evidence from studies indicating that only 3–5% of NSCLC patients are ALK-positive, translating to 28,000–46,000 potential patients globally. Pfizer recently announced a partnership with OxOnc (US) on trials developing the drug for further indications.
How many sales will be generated in China remains to be seen, with the drug unlikely to gain reimbursement for some time. The SFDA approval enables Pfizer to pick a price, and although no pricing details are known as yet the drug could be made available at a similar level to the US, where Xalkori is priced at USD9,600 per month (around USD115,000 per year). In China, Pfizer has made liver and stomach cancer drug Sutent (sunitinib) available to patients through a patient-assistance scheme, and a similar strategy is likely with Xalkori given that reimbursement is unlikely for some time. Xalkori's high cost saw the drug refused reimbursement in Europe last week (see Germany: 20 February 2013: Germany's IQWiG decides added benefit of Xalkori not proven). Given Xalkori's effectiveness, Chinese patients will be hoping that Pfizer can come up with a strategy to make the drug more readily available.
Pfizer's openness to further local partnerships in part reflects difficulties in getting new drugs to market, with the exception of Xalkori. Foreign companies are currently not permitted to carry out first-in-man clinical trials, among other regulatory hurdles. Pfizer's recent activity in China has included setting up a joint venture with Zhejiang Hisun Pharma focused on developing generic drugs, while it has also taken a minority stake in giant distributor Shanghai Pharmaceutical Holdings. Pfizer sees further, broader alliances as likely in future, with both foreign and domestic firms facing pressure on profit margins resulting from the government's price-cutting strategies. The National Development and Reform Commission has cut drug prices four times since 2011, with Pfizer affected by the most recent cuts of up to 20% earlier this year (see China: 9 January 2013: China cuts prices of 400 drugs by average 15%, Big Pharma innovative and generics affected). Greater involvement of multinational firms in China's market would help to improve drug safety levels for consumers, while the recent government reforms are producing much greater market potential in rural areas, where Chinese firms have the advantage of local knowledge, and which foreign firms have so far faced difficulty in penetrating (see China: 25 January 2013: Government health reforms to release pent-up demand in China's county hospitals).
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