炙手可熱的NK細胞:再獲4700萬美元融資

2021年3月18日,生物技術公司Acepodia今天宣佈完成4700萬美元的B輪融資。這筆資金將用於推進該公司領先的現貨off-the-shelfNK細胞治療候選藥物ACE1702針對實體瘤的臨床開發計畫,以及臨床前NK和γδT細胞治療管線進入臨床。

Acepodia是一家美國和臺灣的私營生物技術公司,通過靈活和綜合的生物設計方法重塑細胞治療領域,主要專注於腫瘤學。Acepodia的藥物開發平臺旨在通過嵌合抗原受體技術以及其獨特的ACC(抗體細胞結合)技術來增強免疫細胞的腫瘤親和力,該技術將腫瘤靶向抗體與免疫細胞的表面蛋白連接起來。

ACE1702是該公司研發進度最快的候選產品,是一款抗體-NK細胞偶聯藥物候選產品,目前正在被開發用於治療表達HER2的實體瘤。第一位患者在德克薩斯州休斯頓的安德森癌症中心接受給藥,評估ACE1702對不能接受手術或其他治療方案的晚期或轉移性HER2表達的實體瘤患者的安全性、耐受性、藥效學和初步療效。

炙手可熱的NK細胞

自然殺傷細胞(natural killer cell,NK細胞)細胞在人體的先天免疫系統中起著重要的作用,早在上個世紀70年代,科研人員就對它們進行了描述,但直到最近的15年,人們才逐漸瞭解NK細胞在幫助抗擊癌症和其它疾病方面的複雜性和治療潛力。

NK細胞療法現已經成為一個炙手可熱的領域。NK細胞是人體先天免疫系統的一部分,能對身體內遇到的各種病原體迅速作出反應,是抵禦危險感染或異常細胞的第一道防線,是身體對抗癌症的正常儲備。

目前,各種提高NK細胞效應功能的途徑已經被開發。包括基因修飾的NK細胞正在被研究作為改善過繼性NK細胞療法抗腫瘤活性的手段,例如,CAR-NK細胞、具有修飾形式的CD16的NK細胞(例如Fate公司的FT516,在iPSC來源的NK細胞表面表達不可裂解的CD16 Fc受體,從而優化了ADCC)、和敲除CD38的NK細胞(可以在用針對該蛋白的單克隆抗體治療期間預防中ADCC相關的自損傷)。

在體內增強NK細胞治療活性的輔助方法還包括,基於細胞因數的藥劑(例如IL-12、IL-18和重組IL-15等),NK細胞銜接(engager)分子(例如TriKE,ROCK銜接器,NKCE和TriNKETs)和免疫檢查點抑制劑等。同樣,目前大量增強NK細胞毒性和壽命的方法也在臨床測試中。

2021年02月,中國國家藥品監督管理局藥品審評中心(CDE)受理了國健呈諾生物科技(北京)有限公司的“現貨型”異體來源的CAR-NK產品的臨床試驗申請,也是中國首個獲得CDE受理臨床申報的CAR-NK產品,是免疫細胞治療實體瘤的重要里程碑。

參考資料:

1.https://www.biospace.com/article/releases/acepodia-completes-47-million-series-b-financing-to-advance-pipeline-of-allogeneic-cell-therapy-candidatesprograms-receiving-funding-include-those-developing-company-s-proprietary-cryopreserved-nk-and-gamma-delta-t-cell-candidates/

2年獲投8.5億美元,Biotech公司「裂變式創業」成細胞和基因治療新楷模

美東時間 3 月 15 日,美國生物技術公司 ElevateBio 宣佈完成了 5.25 億美元 C 輪融資,本輪投資由 Matrix Capital Management、軟銀願景基金二期和富達管理研究公司領投,MPM Capital、F2 Ventures、EcoR1 Capital 等原有投資方繼續集結於此。
ElevateBio 將自己描述為 “一家專注于細胞和基因治療細分賽道的生物技術公司”,正在推動和擴展一種 “不同尋常” 的商業模式 ——將細胞和基因療法領域的學術研究,與商業化和規模化量產連接起來,它在其中扮演平臺或者橋樑角色,不斷剝離新公司獨立運營。
ElevateBio 官宣稱,本次所籌資金將用來繼續支援其平臺建設和剝離新公司上。
MPM 孵化而來,創始團隊陣容豪華
“未來 30-50 年,哪項技術將會發生顛覆性變革”?David Hallal、Vikas Sinha、Mitchell H. Finer 等一直在思考這一問題。David Hallal 認為,細胞和基因療法發展空間巨大,這個領域機遇無限,但是還存在許多困難和挑戰。Mitchell Finer 也認為,細胞和基因療法的瓶頸之一在於 —— 規模化量產,比如說藍鳥在入行 8-9 年後才建立了生產設施。
細胞和基因療法領域機遇和挑戰並存,一方面細胞和基因療法市場發展潛力巨大,根據德勤發佈的相關資料,全球細胞和基因療法市場規模有望在 2025 年超過 119.6 億美元;另一方面,該領域也存在生產、製造、遞送等難題,技術仍有待取得突破。
基於這一考慮,他們決定成立一家專注于細胞、基因治療細分賽道的生物技術組合公司 ——ElevateBio。該公司最初由美國著名生物醫藥風投 MPM Capital 孵化而來,2017 年成立以後一直處於隱匿模式中。自 2019 年 5 月以後,ElevateBio 已經籌集近 8.5 億美元資金,成為該領域名副其實的新銳 “吸金王”。(來源:生輝根據公開資料整理)
不過,ElevateBio 並沒有聚焦某種方法或某種疾病,而是將特別關注免疫療法、再生醫學或體內基因療法。
其創始團隊陣容豪華。首席執行官 David Hallal 在生物製藥領域擁有近 30 年經驗,曾是罕見病巨頭 Alexion 的掌舵人,説明 Alexion 從一家單一產品公司過渡到多產品組合公司;首席財務官 Vikas Sinha 在生命科學領域擁有超 25 年財務高管任職經驗,在 Alexion 任職 11 年期間,Alexion 的市值從 6 億美元增長到超過 300 億美元;首席科學官 Mitchell H. Finer 是 MPM Capital 的執行合夥人,此前他是基因療法先鋒藍鳥的 CSO。
並非 CDMO,商業模式清晰
ElevateBio 官方宣稱,正在以一種顛覆性的高效資本模式加速細胞、基因治療的創新速度。這種 “顛覆性” 模式在於,ElevateBio 並不是一個 “單純” 的生物技術公司,研發和搭建專有生產管線,而更像是一個 “平臺型” 公司,不斷孵化該細分領域內不同的新公司。這種模式將專業團隊、資源和資本整合在一起,與科學創始人、醫療中心和企業家們合作不斷推出新公司。具體來說,ElevateBio 集成並搭建完善的細胞、基因療法技術平臺、專家團隊、基礎設施,通過為科學創始人提供從基礎研究到臨床應用能力的服務,包括研發和製造團隊、製造設施、藥物開發和商業化專業知識。在這種模式下,ElevateBio 剝離的公司們可以共用這些專業技術平臺,和專業研發、臨床開發、製造團隊。這一定程度上加速了資源的流通和共用,也解決了細胞、基因療法領域專業人才緊缺的問題。
一方面,ElevateBio 對於剝離的公司採取了 “集中式資源” 和 “中央研發平臺” 策略,加快研發速率;另一方面,所選方向採用了 “中心輻射” 策略,包括成立基因編輯技術、細胞療法、基因療法公司。
而實現這些策略的底層技術在於其技術平臺 ——BaseCamp,這是 ElevateBio 專注於研發、工藝開發和 cGMP 製造的子公司,為 ElevateBio 投資組合公司和部分戰略合作夥伴提供細胞、基因專業技術支援,包括 cGMP、分析和品質控制實驗室、蛋白質工程、病毒學和免疫學實驗室。

提供技術、專家服務的 ElevateBio 是否可以看做是一家 CDMO 公司?
Mitchell H. Finer 曾這樣描述 ElevateBio 的商業模式:“我們不是一家 CDMO 公司, 我們與戰略合作夥伴互惠互利,為患者提供創新產品。”
基因、細胞療法 CDMO—— 通過製造產品積累大量產品資料,然而生物製藥公司卻無法使用集中的資料; ElevateBio 所做的事情類似於把基於 CDMO 平臺累計的資料實現技術、資源集中與共用。
自成立以來,ElevateBio 已經孵化剝離出了三家公司 —— 病毒特異性細胞療法公司 Allovir,T 細胞療法公司 HighPassBio 和基因編輯療法公司 LifeEDIT Therapeutics,並與麻省總醫院建立了 10 年的合作關係。ElevateBio 在一份聲明中表示,還有其他剝離出來的公司,但尚未公開披露。 “我們預計 BaseCamp 的設施能夠容納多個投資組合公司,我們的戰略是成為這些投資組合公司的主要股權持有者。但是隨著時間的推移,我們的持股比例會下降。因為,我們希望這些公司通過 IPO 上市,然後繼續從專業團隊、新成立公司中獲益。” David Hallal 這樣說。
未來,中國完全有可能出現同類型的公司
與 CDMO 不同,ElevateBio 可能更像是一家集投資、孵化與 CDMO 於一身的公司。這也是本公司非常看好其模式的原因:無論是資本模式,還是業務模式、組織結構及資源配置上,這種模式優勢顯著。
“從資本模式來看,這可以實現基於同一技術平臺的多個應用方向並行發展,可以有效降低風險;從業務模式來看,這是一種‘自營式’新藥研發 CRO/CDMO,與傳統的 CRO/CDMO 相比,體系內部配合效率更高;從組織模式來看,這可以看作一種內部孵化的‘裂變式創業’,每一個創業公司都能夠給予創始團隊更多股權,也能夠給到團隊更大的激勵和經營自主權,發展更有動力;從資源配置來看,其類似於‘中台’,共用技術和資源,可以實現更高的資源利用率。這種內部分化發展的模式其實也適用於更多領域,只要是平臺型技術都可以這樣做。其實就是基於同一技術的不同應用方向,孵化出不同的公司,比如說根據 mRNA 設計、遞送技術、基因編輯、合成生物學技術都可以剝離出新公司。
“ElevateBio 的模式可以很好地解決技術、資源分享問題,有利於新興技術得到快速發展和應用。技術的交叉融合越來越成為常態,一種通用的平臺技術在不同領域或同一領域的細分賽道上都會得到應用。
國內是否可以複製這一模式?
Flagship PioneeringFP)的孵化模式不同,這種模式更簡單,更易複製,未來中國完全有可能出現同類型的公司。然而細胞、基因療法的研發速度不在於平臺,而在於技術本身的突破,技術的突破方能真正提高研發速度。
參考資料:

  • https://www.elevate.bio/blogs/elevatebio-scales-disruptive-cell-and-gene-therapy-business-model-with-525-million-series-c-financing

 

您知道身體老化哪10個器官先嗎??

判斷一個人是否衰老,一般會先從他的外表開始觀察,若臉部有皺紋或是有白髮,就會認為他有老化現象。但實際上,人體的很多器官,會在我們外表變老前就先退化了。

據研究指示,一般健康民眾在40歲時,器官功能有80%,而50歲時功能還有70%,但隨著年齡增長,器官功能衰退越快,到了70歲時只剩下35%。

你可能不知道人體最先衰老的器官竟是肺!

一般人在20歲後,肺功能和肺活量就開始出現下降的現象,尤其是到了40歲以後,喘氣吁吁的狀況變得明顯。因為掌管呼吸的肌肉和胸腔變得僵硬起來,使得肺的運轉困難,使得某部分人出現喘氣的狀態:而另一部分人是因為肺功能降低,呼氣後還有一些空氣會殘留在肺部導致喘氣。到了70歲左右肺的呼吸量將僅存30歲時的一半。

其次是皮膚,皮膚約在25歲左右開始自然老化,起因為形成皮膚支柱的膠原蛋白生成速度變慢,加上維持肌膚彈力的彈力蛋白變少或斷裂,而新生細胞的量可能會略微減少,死皮細胞又很慢脫落,導致皮膚彈性變差,皮膚變薄,出現皺紋等老化現象。

平均30歲時,出現落髮、白髮及肌肉老化的問題 落髮問題常見於30多歲的男性,由於左右睪丸激素濃度的改變,導致毛囊收縮,造成新生髮變細的問題,此外,隨著年齡增長,毛囊中的黑色素細胞的活性逐漸降低,使多數人約在35歲時會開始冒白髮。 過了30歲以後,肌肉衰竭的速度開始大於肌肉生長速度,開始出現肌肉老化的現象。

平均35歲時,出現骨骼、乳房及生育能力的問題 骨骼在人生中一直被破骨細胞破壞,再由造骨細胞遞補,這個過程稱為「骨轉換或骨再生」。兒童時,骨再生的速度很快,約2年左右;成年時,骨再生的速度大約需要10年。25歲前,骨質密度會一直增加;但在35歲時,骨質會開始流失老化,造成骨質疏鬆的現象。 女性乳房組織和脂肪會從35歲開始消失,造成乳房變小、影響豐滿度。到了40歲後,乳房的老化現象為乳暈急劇收縮和乳房下垂。而生育能力在35歲後,女性也受到卵巢中卵子的數目和質量降低,造成子宮內膜變薄,使受精卵難著床;在男性方面,精子的品質下降,讓生育能力下降,也使得妻子流產的機率變高。

平均40歲時,腦、牙齒、眼睛和心臟開始老化 人到了40歲,每天會減少1 萬個腦神經細胞,因此對於記憶力及大腦功能造成影響;唾液可以減少牙周細菌的生長,但40歲以後唾液變少,使得牙周細菌容易讓牙齒和牙齦更易腐爛,當牙周的牙齦組織流失後,會造成牙齦萎縮。 隨著年齡的增長,眼部肌肉變得漸漸無力,降低了眼睛的聚焦能力,約40歲左右會開始出現老化眼的現象; 而心臟會因為血管慢慢失去彈性,向全身輸送血液的效率降低。

40歲後,肌肉將逐年減少0.5%~2%,每10年約減少8%的肌肉量。因此,經常做肌力訓練可以預防肌肉老化及肌少症。

平均50歲時,腎和前列腺開始老化 腎過濾血流中的廢物的能力開始降低,容易晚上起床上廁所,75歲老人的腎過濾的能力只有30歲時的一半;前列腺吸收大量睪丸激素會加快前列腺細胞的生長,引起前列腺增生,造成小便次數的增加。

平均55歲時,腸和聽力開始衰退 55歲後,腸內的益生菌細菌會開始大幅減少,使消化能力降低,增加腸道疾病的風險。而隨著年齡增長,胃、肝、胰腺、小腸的消化液流動開始下降,也會提升便秘的機率。而此時,老化也會造成負責接受聲音振動的「毛細胞」傷害,導致聽力受損。

平均60歲時,味覺和嗅覺開始退化 60歲時,味蕾從10000個減少成5000個,而嗅覺也因為嗅覺細胞的老化,造成味覺和嗅覺逐漸衰退。

平均65歲時,膀胱和聲音開始老化 65歲時,我們更有可能喪失對膀胱的控制,尤其是肌肉的伸縮性下降,引起上廁所的次數更為頻繁。一般而言70歲的膀胱容量只有30歲時的一半;而喉嚨的聲帶組織弱化,影響聲音的音質、響亮程度和質量,使得女人的聲音變得越來越沙啞,音質越來越低;而男人的聲音越來越弱,音質越來越高。

平均70歲時,肝臟衰老 肝臟似乎是體內唯一能對抗老化的器官。進行切除部分肝臟手術後,3個月之內它就會長成一個完整的肝。如果捐肝者不飲酒不吸毒,沒有患過傳染病,一個70歲老人的肝也可以移植給20歲的年輕人!

健康是一切根本,精準與大家一起為維護健康而努力。

癌症反復復發,高劑量的化療副作用難忍,在消滅癌細胞同時也在損傷健康細胞,感覺身體每天都在被掏空……就這樣往復無終日的活著,似乎是每個晚期癌症患者的真實寫照。

J.C.Cox患有非霍奇金淋巴瘤,他接受了長達12年的化療,那是一個漫長又艱難的過程。因此,當一個新的嘗試出現之時,JC毫不猶豫的做了選擇,成為了世界上為數不多接受CAR-NK細胞治療的人。

而結果也遠遠超出JC的想像:完全緩解,可以說,他的癌症痊癒了!

與所有癌症患者一樣,JC的癌症之路也充滿艱辛與坎坷。

最初,在醫院診斷出濾泡性淋巴瘤後,66歲的JC驚呆了,“我以為我感染了病毒,我從未想過癌症。”就這樣,在家附近的一家醫院接受定期化療,病情緩解了13個月,但癌症還是復發了。

在忍受了三次高劑量化療後,本以為會有所好轉,但結果卻更為惡劣,因為化療在消滅癌細胞的同時也消滅了許多健康細胞,這使得JC更易受感染,持續治療的四個月後,癌症又一次復發。

於是,JC在醫生的推薦下來到了MD Anderson,尋求淋巴瘤的治療選擇。在這裡,他接受了一種免疫治療藥物的臨床試驗,這種藥物可以訓練免疫系統發現並攻擊癌細胞,這本是好事,但在JC身上,它的副作用實在太大了,JC持續高燒,昏迷不醒,最後只能靠生命維持,“最後他恢復了,我們都松了一口氣”,JC妻子回憶道。

後來的JC只能依靠藥物阻止癌症在體內的擴散,但藥物無法消除癌症,直到JC的濾泡性淋巴瘤轉化為彌漫性大B細胞淋巴瘤,一種更具侵襲性的疾病。

JC的臉上和太陽穴都長了腫瘤,化療每兩周復發一次,病情在持續惡化,而每次積極的化療,也只能讓癌症遠離幾個星期而已,“就好像一場賽跑,癌症要贏了,而我們需要趕快做點什麼了。”JC表示。

新的嘗試:CAR-NK療法

就在JC可以接受的治療選項越來越少的時候,一項新的臨床試驗CAR-NK細胞治療在MD Anderson啟動,而JC的生命也得以重啟。

與已經獲批上市,名聲顯赫的CAR-T細胞療法類似,新的臨床試驗將把CAR加入自然殺傷細胞(NK細胞)上,讓這些細胞潛伏在體內,來更精准的識別並殺死癌細胞。

CAR-NK細胞

NK細胞是人體先天免疫系統重要的一員,本就擅長在早期識別癌細胞並將其摧毀,但狡猾的癌細胞可以發展處躲避免疫系統的方法,而通過改造NK細胞,給他安裝個子彈頭“CAR”,就能夠擴展其天生的抗癌能力,讓自然殺傷細胞更加名副其實。

多劑量的CAR NK細胞可以從一個供體中製造出來,這些可以用來治療多個病人,由於其獨特的特性,CAR NK細胞有可能被提前製造、冷凍和儲存,並立即提供給任何需要的患者。

也多虧了CAR-NK細胞療法的及時出現,JC在治療僅僅30天后,他的情況有了好轉,2018年4月,JC的癌症得到了完全緩解,幾乎可以理解為“治癒”了。

這項研究結果也於2020年3月發表在《NEJM》(新英格蘭醫學雜誌)上,在臨床試驗中的11名患者,包括JC在內的7名患者病情完全緩解,意味著所有癌症症狀和體征都消失了。

 

儘管這只是一項小型研究,但這些有希望、令人興奮的結果將給更多有需要的患者一種有效的新治療選擇。

CAR-NK療法,臨床有效率高達73%
在這項實驗中,CAR-NK展現出了比CAR-T更優秀的臨床效果。

我們都知道,困擾CAR-T的最大問題就是細胞因數風暴,而CAR-NK細胞在體內幾乎不會發生免疫排斥反應,不會產生如此嚴重的副反應,因此,安全性更高。

在本次臨床實驗中,靶向CD19的同種異體CAR-NK細胞療法Ⅰ/Ⅱ臨床試驗研究結果顯示:在接受治療的復發性/難治性CD19陽性腫瘤(非霍奇金淋巴瘤或慢性淋巴細胞白血病)患者中大多數對CAR-NK細胞有反應,且沒有嚴重的毒性作用出現。

在參與這項臨床研究的11名患者中,8人(73%)對CAR-NK治療有反應,其中7人完全緩解,而沒有出現重大毒性作用。並且在所有劑量水準輸注3天內可見,注入的CAR-NK細胞擴增並以低水準持續至少12個月。

CAR-NK細胞的給藥與細胞因數釋放綜合征,神經毒性或移植物抗宿主病的發展無關,並且包括白細胞介素6在內的炎性細胞因數的水準也沒有增加。

臍帶血NK細胞:來源廣泛,安全,抗癌更廣譜
NK細胞,本就是病毒感染細胞和腫瘤細胞的最佳殺手,它們具有天然的殺敵能力,並與T細胞、B細胞一樣具有免疫記憶功能,在同種抗原刺激下,可以快速啟動二次免疫,發揮更強的免疫應答。

在抗擊癌症上,NK細胞還是最有效的廣譜抗癌細胞,NK細胞不顯示腫瘤殺傷的特異性和MHC限制性,在機體其它免疫細胞(如T、B細胞)功能低下時,NK細胞的作用尤為重要,且NK細胞對幾乎所有常見的癌細胞類型都有殺傷作用,包括肺癌、乳腺癌、肝癌、淋巴癌、食道癌等。而NK細胞的殺敵方式也不拘泥於一種,它的抗癌機制非常多樣。

更為重要的一點,NK細胞來源非常廣泛,可以從健康人或者臍帶血中提取出,從而減少患者等待時間,在治療費用上也更經濟。

在眾多NK細胞來源中,臍帶血NK細胞因更加年輕、增殖能力更強、靶向殺傷癌細胞效率更高、收集和冷凍保存更便利等優勢備受矚目,前景可期。

相比于外周血NK來源,臍帶血NK的來源也要更加廣泛,在GMP標準下進行臨床級別的擴展,使臍帶血來源的NK細胞成為癌症免疫治療的“現成”產品。而CAR-NK因來源廣泛,更易獲取,殺瘤廣泛而著稱,並有望成為對所有癌症患者都更有效,更經濟,更安全的療法,我們也期待科學不斷發展,NK細胞帶給癌症患者更多希望。

參考資料:

[1]https://www.mdanderson.org/publications/annual-report/annual-report-2019/with-car-nk-therapy-natural-killer-cells-live-up-to-their-ominous-name.html

[2]https://www.nbcnews.com/health/cancer/immune-therapy-tweak-offers-new-hope-blood-cancer-patients-n1131101

Overview of Hong Kong Cancer Statistics of 2018

 

 

 

  1. Background

 

  • The Hong Kong Cancer Registry (HKCaR) is a population-based cancer registry responsible for collecting the basic demographic data, information of the cancer site, and cancer histology of patients diagnosed with cancer in public and private medical institutions in Hong Kong. Robust cancer registry data provide the basis for governments to prioritise resources in cancer control according to the burden of various cancers in the communities, for health care planners and researchers in developing healthcare policies to improve the quality of cancer care, prioritizing costly cancer treatments, and implementing cost-effective cancer prevention strategies such as cancer screening programmes and other public health

 

  • This is the annual overview of cancer statistics in Hong Kong that provides population-based data highlighting cancer incidence and mortality rates for 2018 and key trends for major In addition, this paper presents, for the first time, the stage-specific survival of breast and colorectal cancers.

 

2.     New cancer cases in 2018

 

  • A total of 34,028 new cancer cases were diagnosed in Hong Kong in 2018, hitting a record high with 953 more cases or a rise of 2.9% compared to the preceding year. On average, 93 people were diagnosed with cancer each

 

  • Of these new cancer cases, 17,040 were diagnosed in males, and 16,988 in The numbers have increased by 164 (or 1.0%) for males and 789 (or 4.9%) for females compared to 2017. The crude annual incidence rates of cancer per 100,000 population were 499.7 for males and 420.4 for females in 2018.

 

  • The five most commonly diagnosed cancers in 2018 were colorectal cancer (16.6%), lung cancer (15.4%), breast cancer (13.7%), prostate cancer (6.5%) and liver cancer (5.1%), accounting for about 57% of new cancer cases diagnosed in Hong Kong in 2018. Compared with the preceding year, colorectal cancer remained stable with 5,634 cases while lung cancer increased by 1.4% to 5,252 cases and female breast cancer increased by 5.6% to 4,618

 

  • In 2018, the increase in the number of new cancer cases was mainly attributed to the growing numbers of bladder and pancreatic cancers in men, breast and corpus uteri cancers in women, as well as thyroid cancer in both

 

  • For males, the top five cancers comprised about 63% of new cancer cases. They were cancers of the colorectum (19.1%), lung (19.0%), prostate (12.9%), liver (8.0%) and stomach (4.3%). They all have the number of new cases less than that in

 

  • For females, the five leading cancers were cancers of the breast (27.2%), colorectum (14.0%), lung (11.8%), corpus uteri (6.9%) and thyroid (4.7%), accounting for around 65% of new cancer cases in

 

  • The number of newly diagnosed invasive breast cancer in women reached over 4,600 in 2018. This marked an increase of 5.6% from 2017. In addition, 669 cases of in-situ breast cancer (i.e. stage 0 breast cancer or called pre-cancer) were diagnosed, which together recorded about 5,300 new cases of invasive and in-site breast cancer in

 

  • Cervix cancer showed a marked increase in the number of new cases compared with that of 2017, by 8% or 582.

 

  • The number of newly diagnosed thyroid cancer reached over 1,000 for the first time in 2018, making it the 9th most frequent cancer in Hong There was an increase of 27.6% and 14.7% in men and women, respectively. The increase was mostly accounted for by the number of micropapillary carcinoma. During the same period, there were only 50 reported deaths from thyroid cancer, indicating an overall good prognosis of this cancer.

 

  • Compared to 2017, there was an increase of 6% in the number of newly diagnosed pancreatic cancer, up to a total number of 855 cases. The number has increased by 91% since 2008. Although pancreatic cancer only being the 11th most common cancers, it was the 5th leading cause of cancer deaths in Hong Kong with 711 deaths recorded in 2018, indicating an overall poor prognosis of this cancer.

 

  • Compared to a decade earlier, new cancer cases have jumped by about 38% or at an annual rate of 3.3%. During the same period, the population grew slowly at an annual rate of 0.7%, but the population aged 65 and older increased at 7% per year.

 

  • As cancer incidence rates increase sharply with age, the increase in overall cancer incidence rate in Hong Kong is largely driven by an ageing and growing population, along with changes in cancer risks as well as the improvements in diagnostic

 

  • The type and order of five leading cancers have remained more or less the same over the years (Table 1). The biggest increases over the past decade were in colorectal cancer among men and breast cancer in women, with about 44% and 77% inclinations in the number of new cases, The annual number of new cases of liver cancer has remained stable in recent years.

 

Table 1. Leading cancer types (both genders combined)

Rank in

2018

Cancer type No. of new cases

in 2008 (rank)

No. of new

cases in 2018

Overall

change

All cancers 24,635 34,028 +38.1%
1 Colorectum 4,031 (2) 5,634 +39.8%
2 Lung 4,236 (1) 5,252 +24.0%
3 Breast 2,633 (3) 4,645 +76.4%
4 Prostate 1,369 (5) 2,204 +61.0%
5 Liver 1,745 (4) 1,742 -0.2%

 

3.        Cancer deaths registered in 2018:

 

  • Cancer was the number one killer in Hong Kong in 2018 with 14,594 cancer deaths, accounting for 30.7% of all deaths in Hong Kong. Over half (58%) of the cancer deaths were in men. The crude annual mortality rates of cancer per 100,000 population were 250.0 for males and 150.2 for females in

 

  • The top three causes of cancer deaths were lung cancer (26.4%), colorectal cancer (15.9%) and liver cancer (10.2%), which accounted for over half of all cancer

 

  • For males, cancers of the lung (29.6%), colorectum (15.4%) and liver (12.8%) accounted for nearly 60% of the cancer

 

  • The cancers causing most deaths in females were lung cancer (21.9%), colorectal cancer (16.6%) and breast cancer (12.4%), accounting for nearly half of all cancer

 

  • Over the past decade, the number of cancer deaths has risen at an annual rate of 1.6% per year. The ranking of top five deadliest cancers almost unchanged (Table 2). There were marked increases in the number of deaths from pancreatic cancer (66.9%) and breast cancer (46.8%). The increase was much less pronounced in lung cancer (10.2%).

 

Table 2. Leading cancer deaths (both genders combined)

Rank in

2018

Cancer type No. of deaths in

2008 (rank)

No. of deaths in

2018

Overall

change

All cancers 12,456 14,594 +17.2%
1 Lung 3,497 (1) 3,853 +10.2%
2 Colorectum 1,686 (2) 2,314 +37.2%
3 Liver 1,499 (3) 1,487 -0.8%
4 Breast 515 (5) 756 +46.8%
5 Pancreas 426 (6) 711 +66.9%

 

  • The increase in the number of new cancer cases and cancer deaths was primarily attributed to an ageing and growing population. As long as the current demographic trends continue in Hong Kong, we shall be witnessing an elevated incidence and mortality burden of cancer in the

 

Appendix 1 displays the ten cancers with the largest number of new cases diagnosed and cancer deaths by gender in 2018.

 

4.        Cancer and gender

 

  • More men developed cancer than women but the difference narrowed to 52 cases in 2018. With the prevailing trends in incidence and population structure, it is expected that females will suppress males in the number of cancer cases in the next few years.

 

  • The cancers with the highest male to female ratio were cancers of the larynx (male to female ratio=14.7:1), oesophagus (4.5:1) and liver (3.5:1).

 

  • The only two cancers that were more common in women than men were thyroid cancer (female to male ratio=3.5:1), and breast cancer which just a mere 6% developed in men.

 

  • More men died from cancer (8,526) than women (6,068), with a male to female ratio of 4 to 1.

 

5.        Cancer and age

 

  • Cancer is primarily a disease of older people. Half of cancers occurred in people over the age of 65, whereas only a mere 0.6% of cancers being diagnosed in children and adolescents (i.e. aged 0-19 years).

 

  • Women are more prone to have cancer than men among adults between the ages of 20 and 59 years, mainly due to the relatively high incidence rates of gender-specific cancers of the breast, cervix, corpus uteri and ovary. The age-specific female preponderance was most apparent in the age group of 20-44 years, in which the number of cancers in women was more than twice of that in

 

  • The median age of patients at diagnosis of cancer in 2018 was 68 years in men and 62 years in women while the median age of cancer deaths in 2018 was 72 years in both men and

 

  • Among the common cancers in males, the median age at diagnosis was 68 years for colorectal cancer, 70 years for lung cancer, 71 years for prostate cancer, 65 years for liver cancer, and 70 years for stomach

 

  • Among the common cancers in females, the median age at diagnosis was 57 years for breast cancer, 68 years for colorectal cancer, 68 years for lung cancer, 55 years for cancer of the corpus uteri, and 50 years for thyroid

 

  • There were 189 newly diagnosed cancer cases in children and adolescents in 2018, 92 in males and 97 in females. The more common children and adolescent cancers were leukaemia (33.3%), lymphoma (15.9%) and germ-cell and gonadal tumours (12.2%). The top three cancers constituted about 61% of all cancers in children and adolescents.

 

  • In young adults aged 20-44 years, the most common cancer was nasopharyngeal cancer for males and breast cancer for Colorectal cancer retained second place in men.

 

  • In adults aged 45-64 years, the most common cancer was colorectal cancer for males and breast cancer for

 

  • In elderly people aged 65-74 years, lung cancer moved past colorectal cancer to become the most common cancer for males The most common cancer was breast cancer for females.

 

  • In very elderly people aged 75 or older, the most common cancer was lung cancer for males and colorectal cancer for

 

  • A person’s risk of developing or dying from cancer is age-dependent. Based on the cancer statistics collected in 2018, about 1 in 4 men and 1 in 5 women will develop cancer before the age of About 1 in 9 men and 1 in 15 women will die from cancer before the age of 75.

 

Appendix 2 displays the relative frequency of the five most common cancers by gender and age groups in 2018.

 

6.        Trends in incidence and mortality in the last decade, 2009-2018

 

  • Age-standardised rate (ASR) is a statistical measure of the risk of cancer after accounting for the influence of age, which is widely used to measure trends over time or between two different Average Annual Percent Change (AAPC) of ASR was estimated using cancer registry data from 1991-2018 to summarize the trends over the 10-year period from 2009 to 2018. A p-value of less than 0.05 (p<0.05) was considered statistically significant.

 

  • In the period from 2009 to 2018, the overall age-standardised incidence rate (ASI) for all cancers in males seemed to be levelling off after the decline in the past two decades, while a significant trend of increasing ASI in females was observed at an annual rate of 1.3% (p<0.05) in the same

 

  • The age-standardised mortality rates (ASM) were decreasing for both genders, at -2.2% per year (p<0.05) among males and -1.0% per year among females (p<0.05) in that

 

  • Among the common cancers, a significant trend of decreasing incidence (ASI) was most apparent in cancers of the nasopharynx (AAPC: -1.9% in males; -4.4% in females) and liver (AAPC: -2.3% in males; -4.5% in females) in both genders, as well as stomach (AAPC: -1.5%) and lung (AAPC: -2.2%) in males (Figures 1 and 2).

 

Figure 1. Average annual percent change (AAPC)1 of age-standardised rates2 of common cancers over the period 2009-2018, Males

Figure 2. Average annual percent change (AAPC)1 of age-standardised rates2 of common cancers over the period 2009-2018, Females

Notes:

  1. Average Annual Percent Change (AAPC) of age-standardised rates over the past ten years is estimated from joinpoint regression (Reference: Clegg LX, Hankey BF, Tiwari R, Feuer EJ, Edwards Estimating average annual percent change in trend analysis. Statistics in Medicine 2009; 28(29): 3670-82.), based on the available data from 1991 to 2018. An asterisk (*) represents the AAPC is statistically significant from zero at 5% level (p<0.05).

 

  1. Rates are age-adjusted to the age distribution of the World Standard Population of Segi (1960).

 

  • A significant trend of rising incidence (ASI) was observed for cancers of the thyroid (AAPC:

+2.6% in males; +3.8% in females), kidney (AAPC: +3.1% in males; +1.6% in females), pancreas (AAPC: +1.6% in males; +1.6% in females) and non-Hodgkin lymphoma (AAPC: +2.1% in males;

+1.3% in females) in both genders, breast (AAPC: +2.5%), cervix (AAPC: +1.8%) and corpus uteri (AAPC: +3.4%) in females, as well as the prostate (AAPC: +1.6%) and colorectum (AAPC: +0.6%) in males.

 

  • In terms of mortality (ASM), a significant decreasing trend was observed in most cancers, with the exception of pancreatic cancer (AAPC: +2.0% in males; +1.0% in females) in both genders, prostate cancer (AAPC: +1.1%) in males and cancers of the breast (AAPC: +0.6%) and corpus uteri (AAPC: +3.2%) in females. No significant changes were observed in cancer of the cervix in

 

2.        Special issue – First report of stage-specific survival of breast and colorectal cancers in Hong Kong

 

  • Cancer stage is an important prognostic information for people diagnosed with cancer. As such, the HKCaR has made considerable efforts to improve the collection of staging data for prevalent cancers in recent

 

  • As the quality and completeness of the breast cancer (BRC) and colorectal cancer (CRC) staging data are high enough for robust analysis of survival by stage at population level, the HKCaR compiles and presents, for the first time, a report of stage-specific survival of breast and colorectal cancers in Hong Kong, and will continue to do so moving forward to include more prevalent cancers.

 

  • Based on the analysis of survival involving more than 66,000 BRC and CRC patients diagnosed in 2010-2017 with follow-up to 2019, the overall 5-year relative survival rates (RSR) of BRC and CRC were 0% and 58.2%, respectively.

 

  • In other words, compared to a group of similar individuals in the general population who do not have BRC, 84.0% of BRC patients would survive 5 years or more after diagnosis. The 5-year RSR was 3% for stage I, 94.6% for stage II, 76.2% for stage III and 29.8% for stage IV.

 

  • The overall 5-year relative survival rate of colorectal cancer was 58.2%. The 5-year relative survival rates were high for stage I (95.7%) and stage II (87.3%). It dropped to 68.7% for stage III and further declined to 3% for stage IV.

 

Key Messages

 

  • New cancer cases jumped by about 3% in a year, reaching a record high of 34,028 in On average, 93 people were diagnosed with cancer each day.

 

  • The ratio between the number of new cases in men and women has narrowed over time, where men outnumbered women by just 52 cases in

 

  • Colorectal cancer remained the most common cancer in men, while breast cancer was still the leading cancer in

 

  • In men, both the number of new colorectal and prostate cancer cases remained consistently high, despite no further increase being observed in

 

  • In women, the number of new breast cancer cases was still on the rise, with a surge of 6% in 2018 and a rise of 77% over ten years, the biggest rise in number among the top 5 cancers.

 

  • Stage I breast cancer had a 5-year relative survival rate of 99%, which means that these individuals were almost as likely to survive (more than 5 years) as women without the disease in the Stage IV breast cancer had a 5-year relative survival rate of 30%.

 

  • For colorectal cancer, the overall 5-year relative survival rate was 58%. The rates were high for stage I (96%) and stage II (87%). It was 69% for stage III but declined to 3% for stage IV.

 

  • Age-standardised cancer incidence rates for men seemed to be leveled off, with an increasing trend for women observed in the past decade. Both age-standardised mortality rates for men and women had a downward trend during the same

 

  • Age-standardised incidence rates have increased over the past decade in the following cancer sites, indicating the increasing numbers of these cancers in the local population could only be partially attributable to the aging population:
    • Male: prostate, colorectum, non-Hodgkin lymphoma and pancreas
    • Female: breast, cervix, corpus, non-Hodgkin lymphoma, pancreas and thyroid

 

 

 

 

Dr. K.H. Wong

Director, Hong Kong Cancer Registry Hospital Authority

21 October 2020

Appendix 1: Leading Cancer Sites in 2018

10 Most Common Cancers
Male
 

Rank

 

Site

No. of new cases Relative frequency Crude

incidence rate*

Median

age (yr)

1 Colorectum 3,259 19.1% 95.6 68
2 Lung 3,245 19.0% 95.2 70
3 Prostate 2,204 12.9% 64.6 71
4 Liver 1,359 8.0% 39.8 65
5 Stomach 739 4.3% 21.7 70
6 Nasopharynx 634 3.7% 18.6 56
7 Non-melanoma skin 576 3.4% 16.9 70
8 Non-Hodgkin lymphoma 567 3.3% 16.6 67
9 Kidney and other urinary

organs except bladder

513 3.0% 15.0 63
10 Lip, oral cavity and pharynx

except nasopharynx

476 2.8% 14.0 64
All sites 17,040 100% 499.7 68
Female
 

Rank

 

Site

No. of new cases Relative frequency Crude

incidence rate*

Median

age (yr)

1 Breast 4,618 27.2% 114.3 57
2 Colorectum 2,375 14.0% 58.8 68
3 Lung 2,007 11.8% 49.7 68
4 Corpus uteri 1,165 6.9% 28.8 55
5 Thyroid 806 4.7% 19.9 50
6 Ovary and peritoneum 664 3.9% 16.4 54
7 Cervix 582 3.4% 14.4 54
8 Stomach 538 3.2% 13.3 68
9 Non-melanoma skin 531 3.1% 13.1 74
10 Non-Hodgkin lymphoma 441 2.6% 10.9 64
All sites 16,988 100% 420.4 62
Both sexes
 

Rank

 

Site

No. of new cases Relative frequency Crude

incidence rate*

Median

age (yr)

1 Colorectum 5,634 16.6% 75.6 68
2 Lung 5,252 15.4% 70.5 69
3 Breast 4,645 13.7% 62.0 57
4 Prostate 2,204 6.5% 64.6 71
5 Liver 1,742 5.1% 23.4 67
6 Stomach 1,277 3.8% 17.1 69
7 Corpus uteri 1,165 3.4% 28.8 55
8 Non-melanoma skin 1,107 3.3% 14.9 71
9 Thyroid 1,037 3.0% 13.9 51
10 Non-Hodgkin lymphoma 1,008 3.0% 13.5 66
All sites 34,028 100% 456.7 65
10 Major Causes of Cancer Deaths
Male
 

Rank

 

Site

No. of deaths Relative frequency Crude

mortality rate*

Median

age (yr)

1 Lung 2,525 29.6% 74.0 73
2 Colorectum 1,309 15.4% 38.4 74
3 Liver 1,089 12.8% 31.9 69
4 Prostate 468 5.5% 13.7 82
5 Stomach 414 4.9% 12.1 75
6 Pancreas 393 4.6% 11.5 71
7 Oesophagus 250 2.9% 7.3 69
8 Nasopharynx 232 2.7% 6.8 61
9 Non-Hodgkin lymphoma 223 2.6% 6.5 74
10 Leukaemia 210 2.5% 6.2 71
All sites 8,526 100% 250.0 72
Female
 

Rank

 

Site

No. of deaths Relative frequency Crude

mortality rate*

Median

age (yr)

1 Lung 1,328 21.9% 32.9 73
2 Colorectum 1,005 16.6% 24.9 78
3 Breast 753 12.4% 18.6 61
4 Liver 398 6.6% 9.8 79
5 Pancreas 318 5.2% 7.9 74
6 Stomach 273 4.5% 6.8 76
7 Ovary and peritoneum 265 4.4% 6.6 64
8 Cervix 163 2.7% 4.0 61
9 Non-Hodgkin lymphoma 152 2.5% 3.8 77
10 Leukaemia 139 2.3% 3.4 69
All sites 6,068 100% 150.2 72
Both sexes
 

Rank

 

Site

No. of deaths Relative frequency Crude

mortality rate*

Median

age (yr)

1 Lung 3,853 26.4% 51.7 73
2 Colorectum 2,314 15.9% 31.1 75
3 Liver 1,487 10.2% 20.0 71
4 Breast 756 5.2% 10.1 61
5 Pancreas 711 4.9% 9.5 72
6 Stomach 687 4.7% 9.2 75
7 Prostate 468 3.2% 13.7 82
8 Non-Hodgkin lymphoma 375 2.6% 5.0 76
9 Leukaemia 349 2.4% 4.7 70
10 Oesophagus 311 2.1% 4.2 70
All sites 14,594 100% 195.9 72
  • All rates are expressed per 100,000 population. Rates for gender-specific sites are per 100,000 male or female population. Statistics on the number of deaths are provided by the Census and Statistics Department and Department of Health of

 

Appendix 2: Five Most Common Cancers by Gender and Age Group in 2018

Male
 

Age 0-19*

 

Site

No.

of cases

% of all

sites

Leukaemia 30 32.6%
Lymphoma 17 18.5%
Germ-cell and gonadal tumours 14 15.2%
Soft tissue sarcoma 8 8.7%
Malignant bone tumour 6 6.5%
Sympathetic nervous system tumour 6 6.5%
All sites 92 100%
 

Age 20-44

 

Site

No.

of cases

% of all

sites

Nasopharynx 115 14.0%
Colorectum 108 13.2%
Testis 69 8.4%
Thyroid 60 7.3%
Lung 57 6.9%
All sites 821 100%
 

Age 45-64

 

Site

No.

of cases

% of all

sites

Colorectum 1,107 19.5%
Lung 965 17.0%
Liver 587 10.3%
Prostate 474 8.3%
Nasopharynx 373 6.6%
All sites 5,679 100%
 

Age 65-74

 

Site

No.

of cases

% of all

sites

Lung 1,108 20.7%
Colorectum 1,026 19.2%
Prostate 984 18.4%
Liver 426 8.0%
Stomach 231 4.3%
All sites 5,357 100%
 

Age 75 and Over

 

Site

No.

of cases

% of all

sites

Lung 1,115 21.9%
Colorectum 1,018 20.0%
Prostate 744 14.6%
Liver 297 5.8%
Stomach 281 5.5%
All sites 5,091 100%
Female
 

Age 0-19*

 

Site

No.

of cases

% of all

sites

Leukaemia 33 34.0%
Brain and spinal tumours 13 13.4%
Lymphoma 13 13.4%
Germ-cell and gonadal tumours 9 9.3%
Carcinomas and epithelial neoplasms 7 7.2%
All sites 97 100%
 

Age 20-44

 

Site

No.

of cases

% of all

sites

Breast 717 34.6%
Thyroid 268 12.9%
Corpus uteri 161 7.8%
Ovary and peritoneum 149 7.2%
Cervix 140 6.8%
All sites 2,070 100%
 

Age 45-64

 

Site

No.

of cases

% of all

sites

Breast 2,554 34.1%
Colorectum 829 11.1%
Corpus uteri 760 10.1%
Lung 722 9.6%
Thyroid 401 5.3%
All sites 7,500 100%
 

Age 65-74

 

Site

No.

of cases

% of all

sites

Breast 831 24.9%
Colorectum 577 17.3%
Lung 519 15.5%
Corpus uteri 162 4.8%
Liver 114 3.4%
Stomach 114 3.4%
All sites 3,343 100%
 

Age 75 and Over

 

Site

No.

of cases

% of all

sites

Colorectum 856 21.5%
Lung 692 17.4%
Breast 516 13.0%
Non-melanoma skin 262 6.6%
Stomach 191 4.8%
All sites 3,978 100%
  • The classification of cancers in children and adolescents (0-19 years) is based on the morphology according to the “International Classification for Childhood Cancer 1996, IARC Technical Report 29: Lyon, 1996.”, rather than the site of tumour.

 

Note on the use of data:

The numbers of new cases and deaths are important parameters to measure the burden of cancer on local healthcare system. One should keep in mind that the figures are subject to random fluctuations from year to year. Experience tells us that a more reliable comment on the trends of incidence and mortality can only be made after observing over a longer period of preferably at least 5 years or more.

 

 

Suggested citation:

Hong Kong Cancer Registry. Overview of Hong Kong Cancer Statistics of 2018. Hong Kong Hospital Authority; Oct 2020. Available at: https://www3.ha.org.hk/cancereg (accessed [date]).

 

More cancer statistics are available on the website of Hong Kong Cancer Registry: https://www3.ha.org.hk/cancereg

Overview of Hong Kong Cancer Statistics of 2018

1. Background

1.1 The Hong Kong Cancer Registry (HKCaR) is a population-based cancer registry responsible for collecting the basic demographic data, information of the cancer site, and cancer histology of patients diagnosed with cancer in public and private medical institutions in Hong Kong. Robust cancer registry data provide the basis for governments to prioritise resources in cancer control according to the burden of various cancers in the communities, for health care planners and researchers in developing healthcare policies to improve the quality of cancer care, prioritizing costly cancer treatments, and implementing cost-effective cancer prevention strategies such as cancer screening programmes and other public health interventions.

1.2 This is the annual overview of cancer statistics in Hong Kong that provides population-based data highlighting cancer incidence and mortality rates for 2018 and key trends for major cancers. In addition, this paper presents, for the first time, the stage-specific survival of breast and colorectal cancers.

2. New cancer cases in 2018

2.1 A total of 34,028 new cancer cases were diagnosed in Hong Kong in 2018, hitting a record high with 953 more cases or a rise of 2.9% compared to the preceding year. On average, 93 people were diagnosed with cancer each day.

2.2 Of these new cancer cases, 17,040 were diagnosed in males, and 16,988 in females. The numbers have increased by 164 (or 1.0%) for males and 789 (or 4.9%) for females compared to 2017. The crude annual incidence rates of cancer per 100,000 population were 499.7 for males and 420.4 for females in 2018.

2.3 The five most commonly diagnosed cancers in 2018 were colorectal cancer (16.6%), lung cancer (15.4%), breast cancer (13.7%), prostate cancer (6.5%) and liver cancer (5.1%), accounting for about 57% of new cancer cases diagnosed in Hong Kong in 2018. Compared with the preceding year, colorectal cancer remained stable with 5,634 cases while lung cancer increased by 1.4% to 5,252 cases and female breast cancer increased by 5.6% to 4,618 cases.

2.4 In 2018, the increase in the number of new cancer cases was mainly attributed to the growing numbers of bladder and pancreatic cancers in men, breast and corpus uteri cancers in women, as well as thyroid cancer in both genders.

2.5 For males, the top five cancers comprised about 63% of new cancer cases. They were cancers of the colorectum (19.1%), lung (19.0%), prostate (12.9%), liver (8.0%) and stomach (4.3%). They all have the number of new cases less than that in 2017.

2.6 For females, the five leading cancers were cancers of the breast (27.2%), colorectum (14.0%), lung (11.8%), corpus uteri (6.9%) and thyroid (4.7%), accounting for around 65% of new cancer cases in women.

2.7 The number of newly diagnosed invasive breast cancer in women reached over 4,600 in 2018. This marked an increase of 5.6% from 2017. In addition, 669 cases of in-situ breast cancer (i.e. stage 0 breast cancer or called pre-cancer) were diagnosed, which together recorded about 5,300 new cases of invasive and in-site breast cancer in 2018.

2.8 Cervix cancer showed a marked increase in the number of new cases compared with that of 2017, by 12.8% or 582.

2.9 The number of newly diagnosed thyroid cancer reached over 1,000 for the first time in 2018, making it the 9th most frequent cancer in Hong Kong. There was an increase of 27.6% and 14.7% in men and women, respectively. The increase was mostly accounted for by the number of micropapillary carcinoma. During the same period, there were only 50 reported deaths from thyroid cancer, indicating an overall good prognosis of this cancer.

2.10 Compared to 2017, there was an increase of 11.6% in the number of newly diagnosed pancreatic cancer, up to a total number of 855 cases. The number has increased by 91% since 2008. Although pancreatic cancer only being the 11th most common cancers, it was the 5th leading cause of cancer deaths in Hong Kong with 711 deaths recorded in 2018, indicating an overall poor prognosis of this cancer.

2.11 Compared to a decade earlier, new cancer cases have jumped by about 38% or at an annual rate of 3.3%. During the same period, the population grew slowly at an annual rate of 0.7%, but the population aged 65 and older increased at 3.7% per year.

2.12 As cancer incidence rates increase sharply with age, the increase in overall cancer incidence rate in Hong Kong is largely driven by an ageing and growing population, along with changes in cancer risks as well as the improvements in diagnostic practices.

2.13 The type and order of five leading cancers have remained more or less the same over the years (Table 1). The biggest increases over the past decade were in colorectal cancer among men and breast cancer in women, with about 44% and 77% inclinations in the number of new cases, respectively. The annual number of new cases of liver cancer has remained stable in recent years.

Table 1. Leading cancer types (both genders combined)
Rank in
2018 Cancer type No. of new cases
in 2008 (rank) No. of new
cases in 2018 Overall
change
All cancers 24,635 34,028 +38.1%
1 Colorectum 4,031 (2) 5,634 +39.8%
2 Lung 4,236 (1) 5,252 +24.0%
3 Breast 2,633 (3) 4,645 +76.4%
4 Prostate 1,369 (5) 2,204 +61.0%
5 Liver 1,745 (4) 1,742 -0.2%

3. Cancer deaths registered in 2018:

3.1 Cancer was the number one killer in Hong Kong in 2018 with 14,594 cancer deaths, accounting for 30.7% of all deaths in Hong Kong. Over half (58%) of the cancer deaths were in men. The crude annual mortality rates of cancer per 100,000 population were 250.0 for males and 150.2 for females in 2018.

3.2 The top three causes of cancer deaths were lung cancer (26.4%), colorectal cancer (15.9%) and liver cancer (10.2%), which accounted for over half of all cancer deaths.

3.3 For males, cancers of the lung (29.6%), colorectum (15.4%) and liver (12.8%) accounted for nearly 60% of the cancer deaths.

3.4 The cancers causing most deaths in females were lung cancer (21.9%), colorectal cancer (16.6%) and breast cancer (12.4%), accounting for nearly half of all cancer deaths.

3.5 Over the past decade, the number of cancer deaths has risen at an annual rate of 1.6% per year. The ranking of top five deadliest cancers almost unchanged (Table 2). There were marked increases in the number of deaths from pancreatic cancer (66.9%) and breast cancer (46.8%). The increase was much less pronounced in lung cancer (10.2%).

Table 2. Leading cancer deaths (both genders combined)
Rank in
2018 Cancer type No. of deaths in
2008 (rank) No. of deaths in
2018 Overall
change
All cancers 12,456 14,594 +17.2%
1 Lung 3,497 (1) 3,853 +10.2%
2 Colorectum 1,686 (2) 2,314 +37.2%
3 Liver 1,499 (3) 1,487 -0.8%
4 Breast 515 (5) 756 +46.8%
5 Pancreas 426 (6) 711 +66.9%

3.6 The increase in the number of new cancer cases and cancer deaths was primarily attributed to an ageing and growing population. As long as the current demographic trends continue in Hong Kong, we shall be witnessing an elevated incidence and mortality burden of cancer in the population.

Appendix 1 displays the ten cancers with the largest number of new cases diagnosed and cancer deaths by gender in 2018.

4. Cancer and gender

4.1 More men developed cancer than women but the difference narrowed to 52 cases in 2018. With the prevailing trends in incidence and population structure, it is expected that females will suppress males in the number of cancer cases in the next few years.

4.2 The cancers with the highest male to female ratio were cancers of the larynx (male to female ratio=14.7:1), oesophagus (4.5:1) and liver (3.5:1).

4.3 The only two cancers that were more common in women than men were thyroid cancer (female to male ratio=3.5:1), and breast cancer which just a mere 0.6% developed in men.

4.4 More men died from cancer (8,526) than women (6,068), with a male to female ratio of 1.4 to 1.

5. Cancer and age

5.1 Cancer is primarily a disease of older people. Half of cancers occurred in people over the age of 65, whereas only a mere 0.6% of cancers being diagnosed in children and adolescents (i.e. aged 0-19 years).

5.2 Women are more prone to have cancer than men among adults between the ages of 20 and 59 years, mainly due to the relatively high incidence rates of gender-specific cancers of the breast, cervix, corpus uteri and ovary. The age-specific female preponderance was most apparent in the age group of 20-44 years, in which the number of cancers in women was more than twice of that in men.

5.3 The median age of patients at diagnosis of cancer in 2018 was 68 years in men and 62 years in women while the median age of cancer deaths in 2018 was 72 years in both men and women.

5.4 Among the common cancers in males, the median age at diagnosis was 68 years for colorectal cancer, 70 years for lung cancer, 71 years for prostate cancer, 65 years for liver cancer, and 70 years for stomach cancer.

5.5 Among the common cancers in females, the median age at diagnosis was 57 years for breast cancer, 68 years for colorectal cancer, 68 years for lung cancer, 55 years for cancer of the corpus uteri, and 50 years for thyroid cancer.

5.6 There were 189 newly diagnosed cancer cases in children and adolescents in 2018, 92 in males and 97 in females. The more common children and adolescent cancers were leukaemia (33.3%), lymphoma (15.9%) and germ-cell and gonadal tumours (12.2%). The top three cancers constituted about 61% of all cancers in children and adolescents.

5.7 In young adults aged 20-44 years, the most common cancer was nasopharyngeal cancer for males and breast cancer for females. Colorectal cancer retained second place in men.

5.8 In adults aged 45-64 years, the most common cancer was colorectal cancer for males and breast cancer for females.

5.9 In elderly people aged 65-74 years, lung cancer moved past colorectal cancer to become the most common cancer for males again. The most common cancer was breast cancer for females.

5.10 In very elderly people aged 75 or older, the most common cancer was lung cancer for males and colorectal cancer for females.

5.11 A person’s risk of developing or dying from cancer is age-dependent. Based on the cancer statistics collected in 2018, about 1 in 4 men and 1 in 5 women will develop cancer before the age of 75. About 1 in 9 men and 1 in 15 women will die from cancer before the age of 75.

Appendix 2 displays the relative frequency of the five most common cancers by gender and age groups in 2018.

6. Trends in incidence and mortality in the last decade, 2009-2018

6.1 Age-standardised rate (ASR) is a statistical measure of the risk of cancer after accounting for the influence of age, which is widely used to measure trends over time or between two different populations. Average Annual Percent Change (AAPC) of ASR was estimated using cancer registry data from 1991-2018 to summarize the trends over the 10-year period from 2009 to 2018. A p-value of less than 0.05 (p<0.05) was considered statistically significant.

6.2 In the period from 2009 to 2018, the overall age-standardised incidence rate (ASI) for all cancers in males seemed to be levelling off after the decline in the past two decades, while a significant trend of increasing ASI in females was observed at an annual rate of 1.3% (p<0.05) in the same period.

6.3 The age-standardised mortality rates (ASM) were decreasing for both genders, at -2.2% per year (p<0.05) among males and -1.0% per year among females (p<0.05) in that period.

6.4 Among the common cancers, a significant trend of decreasing incidence (ASI) was most apparent in cancers of the nasopharynx (AAPC: -1.9% in males; -4.4% in females) and liver (AAPC: -2.3% in males; -4.5% in females) in both genders, as well as stomach (AAPC: -1.5%) and lung (AAPC: -2.2%) in males (Figures 1 and 2).

Figure 1. Average annual percent change (AAPC)1 of age-standardised rates2 of common cancers over the period 2009-2018, Males

Figure 2. Average annual percent change (AAPC)1 of age-standardised rates2 of common cancers over the period 2009-2018, Females

Notes:
1. Average Annual Percent Change (AAPC) of age-standardised rates over the past ten years is estimated from joinpoint regression (Reference: Clegg LX, Hankey BF, Tiwari R, Feuer EJ, Edwards BK. Estimating average annual percent change in trend analysis. Statistics in Medicine 2009; 28(29): 3670-82.), based on the available data from 1991 to 2018. An asterisk (*) represents the AAPC is statistically significant from zero at 5% level (p<0.05).

2. Rates are age-adjusted to the age distribution of the World Standard Population of Segi (1960).

6.5 A significant trend of rising incidence (ASI) was observed for cancers of the thyroid (AAPC:
+2.6% in males; +3.8% in females), kidney (AAPC: +3.1% in males; +1.6% in females), pancreas (AAPC: +1.6% in males; +1.6% in females) and non-Hodgkin lymphoma (AAPC: +2.1% in males;
+1.3% in females) in both genders, breast (AAPC: +2.5%), cervix (AAPC: +1.8%) and corpus uteri (AAPC: +3.4%) in females, as well as the prostate (AAPC: +1.6%) and colorectum (AAPC: +0.6%) in males.

6.6 In terms of mortality (ASM), a significant decreasing trend was observed in most cancers, with the exception of pancreatic cancer (AAPC: +2.0% in males; +1.0% in females) in both genders, prostate cancer (AAPC: +1.1%) in males and cancers of the breast (AAPC: +0.6%) and corpus uteri (AAPC: +3.2%) in females. No significant changes were observed in cancer of the cervix in females.

7. Special issue – First report of stage-specific survival of breast and colorectal cancers in Hong Kong

7.1 Cancer stage is an important prognostic information for people diagnosed with cancer. As such, the HKCaR has made considerable efforts to improve the collection of staging data for prevalent cancers in recent years.

7.2 As the quality and completeness of the breast cancer (BRC) and colorectal cancer (CRC) staging data are high enough for robust analysis of survival by stage at population level, the HKCaR compiles and presents, for the first time, a report of stage-specific survival of breast and colorectal cancers in Hong Kong, and will continue to do so moving forward to include more prevalent cancers.

7.3 Based on the analysis of survival involving more than 66,000 BRC and CRC patients diagnosed in 2010-2017 with follow-up to 2019, the overall 5-year relative survival rates (RSR) of BRC and CRC were 84.0% and 58.2%, respectively.

7.4 In other words, compared to a group of similar individuals in the general population who do not have BRC, 84.0% of BRC patients would survive 5 years or more after diagnosis. The 5-year RSR was 99.3% for stage I, 94.6% for stage II, 76.2% for stage III and 29.8% for stage IV.

7.5 The overall 5-year relative survival rate of colorectal cancer was 58.2%. The 5-year relative survival rates were high for stage I (95.7%) and stage II (87.3%). It dropped to 68.7% for stage III and further declined to 9.3% for stage IV.

Key Messages

 New cancer cases jumped by about 3% in a year, reaching a record high of 34,028 in 2018. On average, 93 people were diagnosed with cancer each day.

 The ratio between the number of new cases in men and women has narrowed over time, where men outnumbered women by just 52 cases in 2018.

 Colorectal cancer remained the most common cancer in men, while breast cancer was still the leading cancer in women.

 In men, both the number of new colorectal and prostate cancer cases remained consistently high, despite no further increase being observed in 2018.

 In women, the number of new breast cancer cases was still on the rise, with a surge of 5.6% in 2018 and a rise of 77% over ten years, the biggest rise in number among the top 5 cancers.

 Stage I breast cancer had a 5-year relative survival rate of 99%, which means that these individuals were almost as likely to survive (more than 5 years) as women without the disease in the population. Stage IV breast cancer had a 5-year relative survival rate of 30%.

 For colorectal cancer, the overall 5-year relative survival rate was 58%. The rates were high for stage I (96%) and stage II (87%). It was 69% for stage III but declined to 9.3% for stage IV.

 Age-standardised cancer incidence rates for men seemed to be leveled off, with an increasing trend for women observed in the past decade. Both age-standardised mortality rates for men and women had a downward trend during the same period.

 Age-standardised incidence rates have increased over the past decade in the following cancer sites, indicating the increasing numbers of these cancers in the local population could only be partially attributable to the aging population:
– Male: prostate, colorectum, non-Hodgkin lymphoma and pancreas
– Female: breast, cervix, corpus, non-Hodgkin lymphoma, pancreas and thyroid

Dr. K.H. Wong
Director, Hong Kong Cancer Registry Hospital Authority
21 October 2020

Appendix 1: Leading Cancer Sites in 2018

* All rates are expressed per 100,000 population. Rates for gender-specific sites are per 100,000 male or female population. Statistics on the number of deaths are provided by the Census and Statistics Department and Department of Health of HKSAR.

Appendix 2: Five Most Common Cancers by Gender and Age Group in 2018

* The classification of cancers in children and adolescents (0-19 years) is based on the morphology according to the “International Classification for Childhood Cancer 1996, IARC Technical Report No. 29: Lyon, 1996.”, rather than the site of tumour.

Note on the use of data:
The numbers of new cases and deaths are important parameters to measure the burden of cancer on local healthcare system. One should keep in mind that the figures are subject to random fluctuations from year to year. Experience tells us that a more reliable comment on the trends of incidence and mortality can only be made after observing over a longer period of preferably at least 5 years or more.

Suggested citation:
Hong Kong Cancer Registry. Overview of Hong Kong Cancer Statistics of 2018. Hong Kong Hospital Authority; Oct 2020. Available at: https://www3.ha.org.hk/cancereg (accessed [date]).

More cancer statistics are available on the website of Hong Kong Cancer Registry: https://www3.ha.org.hk/cancereg

2021年既是充滿挑戰的一年,也必然是充滿希望的一年。在醫藥這個日新月異的行業,未來始終值得期待。

01 未來是三類企業交相輝映的時代 經過這些年的發展,中國藥企大致上已經劃分為三類公司:中國式Big Pharma、Biopharma和Biotech公司,發展迅速,且各有特點。 中國式Big Pharma通常是指中國本土的,同時具備強大的銷售能力和研發能力的大型藥企,如恒瑞醫藥、豪森製藥、中國生物製藥、石藥集團、複星醫藥等。此類大型藥企的成長需要更加厚重的時間、經驗和資本積累,且數量較少。對標全球及美國市場,可以合理預測未來我國此類大型藥企數量並不會呈現爆發式增長,保持在個位數量級。 這類公司基本上擁有“立項-臨床-申報上市,市場准入-學術推廣-終端管道”完整的六大能力,能夠實現一個產品的全生命週期佈局,並在多個科室同步實現規模化銷售。此類藥企由於自身資金及研發實力的優勢,可以迅速佈局熱門靶點,“Fast Follow”等管線,並結合自身強大的銷售能力保證銷售情況以及回報。中國式Big Pharma目前說來業務仍然以國內市場為主,在充分發揮國內管道、資源優勢的前提下,兼顧海外業務。未來發展的重點為拓展海外Biotech等公司優秀產品中國區的研發及銷售權益,幫助鞏固自身的龍頭地位。 與Big Pharma相比,中國式Biopharma的發展則更為迅速,其特徵為體量介於大型Big Pharma和小型Biotech公司之間;通常佔據細分賽道的領先地位,有明顯長板;國內外市場兼顧,同時發展國內銷售和國外合作權益。此外,中國式Biopharma在資本加持下,市值有時也不輸於頭部Big Pharma,且這種資本市場的認可會產生一定的“反身性效應”。信達生物、百濟神州、貝達藥業、君實生物等一批實現了產品規模化銷售的企業是中國式Biopharma典型代表。 但相比於Big Pharma,中國式Biopharma全領域整合能力較弱,但通常在細分領域的研發積累、特定技術的研究深度具有優勢,從研發方向和管線上避開與大型藥企的“頭對頭”直接競爭,保持細分賽道中的領先地位,或在細分賽道可以與大型龍頭公司相競爭。 如果說前兩類的企業在中國數量相對有限,那麼眾多Biotech的設立未來仍將如雨後春筍般持續。 若將Big Pharma比作一個由多塊“木板”拼成的“木桶”,那麼Biotech只是一塊板,前者需要的是“無短板”,後者則需要把“長板”做的更長。 從某種意義上說,Biotech公司並不需要建設龐大的銷售團隊,更多會以產品授權方式獲得收益,而收益的大小,取決於其資產在國內和國際上的獨特性。 無論是哪類企業,創新藥相關標的長期來看仍將是高確定性的產業贏家。考慮到中國龐大的醫藥市場和未來國際化水準的提升,國內整體醫藥市場的龍頭企業和細分行業的領先企業遠期市值空間依然值得期待。
02 未來是中國藥企國際化的時代 隨著中國加入ICH、審評積壓解決、帶量採購倒逼等因素,近年來醫藥企業創新藥在國內註冊申報數量顯著增長;進口新藥審批明顯加速,同時國內與國際獲批時間的“時差”亦在顯著縮短;自醫保談判實行,各家藥企穩固的價格體系逐漸被破除,可以預見,隨著中美審批時間視窗差越來越短,醫保支付體系越發科學,以藥物經濟學特性為核心的定價支付體系將逐步形成。簡而言之,未來的產業格局會要求企業回歸一個最本源的目標——做好藥,滿足那些未被滿足的醫療需求,而這就需要更大級別的研發投入。 相關資料顯示在2015年前,中國醫藥企業沒有一家研發費用超過10億人民幣,而到了2020年,已經有企業的投入超過了10億美元,在這一背景下,研發的回報就不能僅僅依靠國內市場,而是必須走向全球。
隨著國內創新藥企業研發水平的不斷提升,重磅藥物靶點佈局愈發完善,潛在BIC或FIC產品也不斷湧現;加之中國的人口基數優勢與較高的研發效率,臨床入組與研發推進速度也往往後來居上;NMPA加入ICH後,更是加快了中國創新藥以高性價比優勢惠及全球的步伐。 以PD-1單抗為例,雖然當下業界對該領域的“高水準重複建設”不乏微詞,但部分國產產品一方面有著不輸於“K藥”、“O藥”的療效與安全性;另一方面從國內終端價格來看(不考慮醫保覆蓋),性價比優勢明顯,無論考慮前期研發成本,抑或實際生產成本,利潤空間仍較為豐厚。 作為I-O靶點藥物,PD-1單抗的潛在聯用價值與泛癌種治療市場空間引人遐想,因此,海外藥企License-in臨床進展居前且適應症佈局廣泛的中國PD-1單抗的原因不言而喻。此外,在國內創新藥醫保談判漸成常態的大背景之下,中國創新藥企業也在積極謀求海外市場的開拓。同其他高新技術領域一樣,醫藥生物也正在上演著從“中國製造”到“中國智造”的轉變,從以原料藥出口為主到創新藥專利出海進發。PD-1單抗僅僅是中國創新藥“國際化”進程全面加速的開始,CD47、BCL-2、CAR-T等多個領域也都傳出了國際化的好消息。 可以想像的是,未來只要中國企業能夠在臨床資料上有好的表現,堅持國際標準的臨床,那麼在新一代具有國際背景的企業當家人的帶領下,中國醫藥產品的國際化將成為勢不可擋的新趨勢。

03 未來,值得我們一起期待! 回顧過去20年,中國醫藥產業的變化恍如隔世。 20年前,我們還在關注如何依靠廣告轟炸在基層市場打開OTC產品的銷量。 15年前,我們還在為如何修改抗生素的官能團而煞費苦心。 10年前,我們投入大量精力行銷一批中藥獨家品種。 5年前,我們還在首仿、搶仿的道路上狂奔不已。 而今天,我們會在一起“吐槽”PD-1的熱度過高,不滿我們在EGFR、KRAS這些熱門靶點上Fast follow的太快,亦或是擔心生物類似物的激烈競爭成為了升級版的EPO。 誠然,這些“吐槽”不無道理,但另一方面,這些“吐槽”也成為了中國醫藥產業迅猛發展的有力佐證。我們已經在多年前成為全球第二大藥品市場,現在也成為了全球第二大醫藥投資市場,相信在不久的將來,我們也會繼續在研發上追趕世界領先水準。儘管這確實是一個艱苦而漫長的過程,但當我們回首已經走過的那麼漫長的路,我們沒有理由不抱著樂觀的態度。 在醫藥領域,技術上總是“江山代有才人出”,當我們聽了製藥界前輩們當年創業的故事,再看看我們現在手上擁有的一眾“新式武器”——國際化的CRO/CDMO企業、從DEL到PROTAC的一堆平臺、AI大資料的強力支援,我們便知道,未來我們一定會做的更好。

 

FDA前臨床審批官、國家藥品監督管理局藥品審評中心前首席科學家何如意博士一起探討新藥臨床試驗設計攻略。

01 臨床試驗設計不應該是越花哨越好

E藥經理人如何去定義一個最佳的臨床試驗設計?

何如意:不應該是越花哨的越好,也不應該是患者越多越好。用最少的患者、最短的時間,能夠滿足監管機構的要求,來證明該產品在你所追求的適應證上是有效的、安全的、患者獲益大於風險可能是最佳的臨床試驗設計。為了保證試驗成功,無理由的增加樣品量,這也是不對的。作為監管機構,我們一定要保護受試者,所以並不是患者數越多越好,週期越長越好。

E藥經理人:當前國內新藥新藥臨床設計處於一個什麼樣的水準?

何如意:從過去五年來看,中國新藥研發幾乎是從仿製藥為主逐步過渡到仿創結合的發展過程。五年前很少有新藥研發,大家也不太重視,近幾年逐步開始關注,所以新藥臨床試驗設計也幾乎還是處於絕大多數照抄國外同靶點、同類型藥物的階段,沒有太多思考。但近幾年從CDE的申報資料來看,中國新藥研發有非常大的提高,目前正處於一個非常活躍的階段。

E藥經理人:您覺得造成藥企照抄國外、沒有更多思考的原因是什麼?何如意:中國目前並非處於全新原創藥物的階段,所以最保險、最容易被監管機構接受的就是去照抄和模仿臨床試驗的模式。在這個階段上,就是照抄模仿、從中學習到最後的提高。

E藥經理人:這是由政策造成?還是因為藥企想先盈利的動機?哪個原因更重要一些?

何如意:這其實倒沒有什麼政策的引導,因為這是最省力的、風險最低的。當有突發情況時,譬如2020年新冠疫情爆發時,就凸顯出來我們的臨床試驗設計跟不上,還是按照過去模仿照搬,但又沒有完全一樣的設計,因為新冠太新了,全世界都沒有。你只能用那種很傳統的方法去照搬類似的臨床試驗設計,就像埃博拉病毒、流感,這是一個培養的過程。E藥經理人:去年新冠出來後,很多企業開始研發治療藥物,在像新冠這種全新的藥物研發當中,進步的地方在哪裡?遇到的阻礙又在哪裡?何如意:最開始新冠出來的時候,做什麼樣的臨床試驗設計都有,可謂百花齊放。上百甚至幾百個新冠臨床試驗,有中藥也有西藥,大家都在以過往的模式,用各自的方法在做。但是一年過來了,中國有哪一個臨床試驗真正證明了哪個藥對新冠有效或者證明了對新冠無效。從這麼多臨床試驗我們學到了什麼,這其實也是值得思考的一件事情。

E藥經理人:您覺得導致新冠藥物研發無果的主要問題在哪裡?或者說他遇到的是什麼樣的阻礙?我們應該怎麼去解決?

何如意:最大的問題可能是大家對臨床試驗這門科學的認識並不是那麼深刻,所以才有了五花八門的臨床試驗設計。有的是想圖一些捷徑,以為臨床試驗就是為了應付監管機構,其實並非如此。臨床試驗是一門科學,臨床試驗都源於臨床試驗設計,臨床試驗設計應該如何做、如何完善,最起碼要尊重臨床試驗設計。

E藥經理人:如果從臨床試驗設計到真正把設計方案執行在臨床上,這塊的能力在您看來目前處於什麼樣的水準?

何如意:目前中國的臨床試驗設計能力相比國際大藥廠要差的很遠,主要是中國臨床試驗人才不夠,以前做仿製藥基本都是以生產環節為主,對臨床試驗這個階段也不重視,中國這方面是需要提高的。

E藥經理人:您覺得設計完的方案在醫療機構試驗基地的執行情況,包括主要研究者(Principal investigator, PI)對試驗方案的理解上,與國外有差距嗎?

何如意:臨床試驗並不是什麼高科技,只要按照設計好的臨床試驗方案,最好不要加任何的理解,按照試驗方案執行就好了。所以,這樣的臨床試驗並不需要非常頂尖的科學家。在美國很多臨床醫生都有機會參與,而在中國希望更多的臨床機構更多的臨床醫生參與臨床試驗。

E藥經理人:不同適應證的臨床方案設計有沒有不同,不同在哪裡?

何如意:其實差別挺大的。簡單打個比方,感染性疾病、高血壓、糖尿病、抗病毒等適應證的1期臨床試驗,一般都在健康人身上完成,在此階段就是要找到一個最高的可耐受劑量。但腫瘤藥物1期臨床試驗只能在患者身上完成,這就造成了做腫瘤藥物要有一些非常有別於其他適應證的臨床試驗設計。不過,從1期到2期抗腫瘤的臨床試驗有一定的序貫性,有資料支援可能在臨床2期就實現上市,但其他適應證是不可能的。

E藥經理人:疫情爆發後,國內增加了很多抗病毒抗感染藥的開發,這種新藥要開展臨床的話,需要注意一些什麼?

何如意:這一類的藥物研發,跟腫瘤思路完全不一樣。因為抗病毒藥的作用機制在體外就會得到非常好的驗證。如果在體外抑制不了病毒,或者消滅不了病毒,在體內要想測出好的結果,基本上是不可能的。所以,這一類的臨床試驗常常是1期、2期的成功率遠遠要高於腫瘤和其他適應證。

E藥經理人:單藥和聯合療法會不會也有不一樣?要注意一些什麼?

何如意:單藥最基本就是要證明單藥的安全有效,如果是兩個未知新藥,那麼A和B做聯合,需要證明A有效、B有效,證明A+B>A也大於B。除非已知其中一藥無效或只是增加另一藥的療效吸收或排泄。

02 研發一定要差異化

E藥經理人:當前很多創新藥企臨床試驗採用國際多中心方式,如何去做好一個成功的臨床試驗設計?

何如意:國際多中心涉及挺多方面,首先要面臨不同的監管機構,比如中國和美國,成功的第一步就是臨床試驗設計一定要符合中美兩個國家監管機構的認可,所以需要瞭解兩個監管機構的異同點。第二,不能單純為了國際多中心而做國際的申報,臨床試驗一定是要相互支援的,不能簡單的重複。目前中國有很多為了走國際化重複申報的例子。

E藥經理人:同一個臨床試驗在多中心同時開展,但進度完全不一樣,您覺得是什麼在影響他們的進度?

何如意:對於美國FDA或者歐盟已經審評審批過的國際多中心臨床試驗,如果沒有特殊必要的修改,我們基本同意企業按照美國或者歐盟審批過的方案去進行,目的是增加中國研究者和研究機構參與國際多中心的機會,通過參與他們能夠有所提高。中美進度不一致現象其實非常明顯,這也是為什麼我更喜歡在中國做臨床試驗的原因。中國患者基數大,美國相對要少得多,尤其是一些特殊的疾病,例如肝癌、胃癌,還有一些罕見病,在美國招募患者非常困難。另一個是工作流程也不盡相同,譬如在美國一般都要找國際CRO,而在中國很多時候大公司都有自己的臨床團隊,能夠控制這個進度。

E藥經理人:現在我們知道美國的臨床試驗資料一般是可以支援中國的新藥上市申請,但是中國的臨床試驗資料應該還沒法支援到美國,對吧?何如意:其實並非如此,中國接受境外臨床試驗資料支援新藥上市申報是近年才開始的,目的就是為了能夠讓國內患者儘快地享受到國際上最先進的醫藥新產品,減少重複試驗以降低成本。在美國,其實並沒有嚴格意義上的美國產還是國外產,臨床試驗資料絕大部分都來自美國之外。所以FDA的標準就是只要企業提交的臨床試驗資料符合要求,按照FDA的指南,不管在哪做臨床都可以支援申報。其實中國目前也是朝著這個方向在努力,所以中美之間沒有障礙,只不過很多人可能沒有意識到美國FDA的接納性是更高的。

E藥經理人:我們看到四個國產的PD-1在中國已經獲批了很多適應證,但他們在美國提交的適應證並不是在中國已經獲批的那些適應證,您怎麼看這個事情?

何如意:一個產品到美國到中國能否快速利用某些政策快速上市,譬如有條件批准,是按適應證比目前可獲得的治療更好。這和某個藥基本上關係不大。如果已經有了類似的藥,且擬申請的新藥沒有特殊優勢就不會有特殊待遇,也就是說同樣的適應證能支援中國上市的資料可能並不足以支援在美國有條件批准。所以,這種研發一定要走差異化,要在沒有的適應證上去尋求一個突破。這點中美基本一致,我們是參照美國來實行的。

E藥經理人:這些藥企在出海去FDA申報的路上,會因為把握不好FDA的動向和政策,或者說臨床試驗設計不好導致進度差距拉大嗎?何如意:這種情況也會有。但很多時候跨國大公司決策流程並不占很大的便宜,國內在跟進這些領跑的新臨床試驗設計的能力很強。

03  license in產品一定要雙邊協同,不要簡單重複

E藥經理人:現在國內有很多通過授權引進的創新藥在國內做臨床,如何做好這一類產品的臨床開發以最快的速度實現上市?

何如意:就目前這個階段來說,license in模式應該是快速補充管線的一種方式,因為自主研發過程實在太漫長了,中國目前自主研發能力遠遠落後于國際先進的國家,尤其是美國或歐盟。今後自主研發和license in一定是相輔相成,而且長期伴隨,在未來一段時期,作為中國新藥研發公司的一個基本模式。那麼藥企需要考慮的就是如何利用國外的資料加快中國的申報。license in的兩個公司,一個在國外研發,一個在國內研發,最佳情況就是能夠相輔相成、相互支持,然後快速推進,同時在兩個地區實現上市。很多時候看到一些引進專案協調性很差,合作方擔心中國的臨床試驗耽誤了歐美的試驗或者說中國臨床做的不好,影響了整體的資料。

E藥經理人:為什麼在license in這種合作關係當中,國際的合作方會害怕中國臨床耽誤了歐美的試驗?為什麼會出現這種擔憂?

何如意:其實"722"事件可算做一個分水嶺,如果是“722事件”前的臨床試驗,國際上會有一些擔憂,但“722事件”後,中國在GCP方面已經做得非常好了,可靠性非常好。

E藥經理人: license in模式中產品的臨床試驗設計該如何選擇臨床試驗所在地?

何如意:這要看license in的是一個什麼階段的產品。如果說是一個正處於臨床2期的產品,臨床3期我推薦中美一起做。中國方面,只要證實中國患者跟國際多中心的主體患者群沒有明顯差異就可以免種族差異試驗。不同階段策略不一樣,中國現在可能引進更多的是很早期的產品,那就需要和自己自主研發的管線雙邊協同,而不是簡單重複。

E藥經理人: license in模式會對中國的創新藥企的臨床試驗設計能力有提升嗎?何如意:無論是License in,還是license out,美國公司或者國際大一點的公司臨床設計做得非常深入,考慮因素非常多。在這個過程中,對中國企業也是一個觸動。很多中國企業包括我自己都是急於求成,能不做的就不做,能省的就省。國際這些大型藥企做事情會更踏實,會從不同的層面去論證藥品的品質、可靠性、臨床試驗的資料,這些都會對中國藥企有一個很好的幫助。

E藥經理人:您如何理解藥審體系的持續改革與完善?

何如意:不管是中國、美國,所有國家都有改進的空間,必須承認中國這幾年已經有了很大提高。新藥研發所對應的能力要求越來越細化,不可能一個團隊能覆蓋所有事情。美國已經在這樣做了,譬如他們根據適應證的細化來拆分團隊,現在已經劃成了20多個。此外,還有溝通效率,這在新藥研發當中非常重要。

E藥經理人:從2014年的“替尼熱”,到現在的PD-1熱,接下來可能還有ADC熱,很多公司都紮堆同步進入臨床。您覺得從監管層面來說,是否有責任或有義務來影響企業不要集中熱門靶點嗎?

何如意:這個責任一定是在於企業,而不在於國家。對監管而言,不管是第一個還是最後一個,審評標準都相同。企業在研發過程中,需要有自己的研發策略。如果排在第一位或第一梯隊,可能要找一個儘快上市的適應證,快速把自己的產品推到市場,這時你可能不在乎適應證大小,市場大小。如果排在後面,一定要做差異化的研發策略,然後利用快速批准政策有條件批准上市。對我而言,企業紮堆同一靶點的藥國家一定是樂見其成的,因為做的越多越能提早將那一類藥品推到類似仿製藥階段,一方面可以降低政府支出成本,另一方面可以提高患者對藥品的可及性。

 

縱觀中國發展大勢, 2021年將會發生哪些變化呢?本文先後從個人、企業、國家三個角度詮釋世界變化。

個人篇
1、中國將越來越細分:行業將越來越垂直、協作越來越完善。因此傳統的木桶原理不再成立,以前我們總在彌補自己短板,因為你的短板限制了你的綜合水準,是今後我們將不斷延展自己長處,因為你的長處決定了你的水準。

2、對於每個中國人來說,傳統奮鬥的五大關鍵字:背景、學歷、資源、人脈、資歷;今後奮鬥的五大關鍵字:知識、創新、獨立、個性、理想。以前是學好數理化不如有個好爸爸,現在有個好爸爸,不如自己有文化,中國的“新知識份子”將重登歷史舞臺。

3、中國人正在由“外求”變成“內求”。外求即就求關係、求管道、求機會,內求即是要激發起自己的興趣、熱情、希望,當你做好你自己,外界的東西就會被你吸引過來,這就是所謂的“求人不如求己”。

4、中國正在興起大量自由職業者,社會的基本結構從公司+員工,變成了平臺+個人。每個人都將衝破傳統枷鎖的束縛,獲得重生的機會,關鍵就看你是否激發了自身潛在的能量。這才是一場真正解放運動!

5、中國一大批有“匠心”的人的社會地位將獲得提升,那些腳踏實地的人比如工匠、程式師、設計師、編劇、作家、藝術家等等,因為互聯網已經把社會的框架搭建完成,剩下的就是靈魂填充!所以即便是普通的工作崗位,他們的社會地位也將獲得提升,將獲得尊重。

6、未來每一個人都是一個獨立的經濟體。即可以獨立完成某項任務,也可以依靠協作和組織去執行系統性工程,所以社會既不缺乏細枝末節的耕耘者,也不缺少具備執行浩瀚工程的組織和團隊。
7、原來我們每個人都被木桶原理所束縛,即:你的短板限制了你的綜合水準,所以我們總在彌補自己短板,而隨著人們協作效率的提高。今後你的長處決定了你的水準。我們不用再盯著自己的短板,你只需要將自己擅長的一方面發揮到極致,就會有其它人跟你協作,這叫長板原理。

8、我們的工作正由“被動”走向“主動”。以前為了謀生,我們需要依託固定公司,在固定時間、固定地點重複固定的勞動,屬於被動式勞動。未來社會的總財富是這樣創造出來的:人們依靠自身特長,點對點的對接和完成每一個需求,充分融入到社會每一個環節,屬於主動式創造。

9、對於未來每個人來說,未來有一件東西會變的格外重要,那就是你的信用。未來個人的財富路線是這樣的:行為——能力——信用——人格——財富。在大資料和互聯網的説明下,你的行為推導出了你的信用值,然後以信用度是支點,能力為杠杆,人格為動力,聯合撬動的力量範圍,就是你的財富值,也是你所掌控世界的大小。

10、中國人出名的方式,先後經歷了:公司包裝——參加選秀——成為網紅等三個階段。最開始的時候完全依靠影視娛樂公司包裝,後來流行起了參加各種選秀節目,比如超級女生/中國好聲音等等,現在開始做網紅/女主播等等,關鍵問題是:在互聯網時代,出名不算什麼難事了,難的是擁能夠長期出名的真才實學。

11、原來人與人之間講究的是關係,今後人與人之間講究的是規則。傳統社會的關係網已經被不斷撕裂,以價值分配為關係、新的連結正在形成,每個人都是一個節點,進行價值傳輸。而你所處的地位和層級,是由你所帶來的價值決定的。當人人都在講規則,道德自然就會興起。

12、未來每個人都能擁有自己的產品。如何實現呢?邏輯應該是這樣的:創意——表達——展示——訂單——生產——客戶。當你有一個想法時,你可以先表達出來,然後在平臺上進行展示(這樣的平臺會越來越多),然後吸引喜歡的人去下單,拿到訂單後可以找工廠生產(不用擔心量太少,今後的生產一定會精細化和定制化),然後再送到消費者手裡。

13、原來我們只相信自己的眼睛,所謂眼見為實。但是由於“虛擬實境”技術的逐漸成熟,我們就不再那麼固執了:VR可以讓你置身於任何一個世界裡,AR可以把任何事物帶到你面前。於是眼見再也不為實,今後我們可能只相信自己的內心,只要心一觸念,一切都到了。那麼一切心外之物,皆為虛妄。

14、原始社會人與人之間的關係是“交換”,奴隸社會人與人之間的關係是“奴役”,封建社會人與人之間的關係是“剝削”,資本主義社會人與人之間的關係是“雇傭”,未來社會人與人之間的關係是“協作”這是人類社會的發展路徑,也是文明進步的階梯,一個環節都不能缺失。

企業篇

15、在消費品市場,國貨運動,方興未艾。越來越多的企業會願意投入到國產品牌的創造中,越來越多的消費者願意為國貨買單。

16、數位化趨勢不可逆,而且被疫情大大提前了,至少加速了6年時間。同時,數位化的未來,是一個分化的未來。數位化對你來說是蜜糖還是毒藥,只取決於你是對人負責,還是對事負責。

18、反壟斷成為科技行業最大變數,短期與長期影響都將十分巨大。二選一、互相遮罩、大資料殺熟等現象將被有效遏制,補貼大戰成為歷史,挑戰巨頭的“老二”們不再非死不可,行業走向良性競爭。

19、更多網紅品牌會出現,但也有更多網紅品牌會死掉,網紅品牌大都逃不過“名不副實終究只能曇花一現”的宿命。

20、中國當下的企業分為三個等級:三等企業做服務——二等企業做產品——一等企業做平臺。企業的出路唯有升級成平臺化,平臺化的本質就是給創造者提供創造價值的機會,把自己變成一個價值創造的平臺,未來所有的公司、企業、組織都將平臺化。
21、原來的企業是橫向發展:越做越大、涉及面越來越寬。因此企業越做越容易展開“同質化競爭”,今後的企業是縱向發展:越做越精,挖掘度越來越深。這種變化使行業將越來越垂直、協作越來越完善。於是中國越來越細分,結構越來越周密,企業與企業之間、行業與行業之間的獨立性越來越強,“差異化共存”成為商業主流。

22、原來一流的企業做“標準”,這是大工業時代的邏輯,所有的產品都是被整齊劃一的,標準的制定者可以坐享其成。今後一流的企業做“服務”,是那種能夠滿足各種消費者、各種需求的服務,往往是定制性的,它對企業的兩方面要求比較高:第一就是提供定制化的能力(科技),第二就是對接消費者的能力(互聯網)

23、中國電子商務進化論:B2B——B2C——C2C——C2B——C2F從商家對商家、到商家對個人、個人對個人,個人對商家、最終是個人對工廠。未來每一件產品,在生產之前就知道它的顧客是誰,個性化時代到來,乃至跨國生產和定制。

24、中國互聯網的進化論:傳統互聯網——移動互聯網——萬物互聯,傳統互聯網就是PC互聯網,它解決了資訊對稱;移動互聯網解決了效率對接;未來的物聯網需要解決萬物互聯:資料自由共用、價值按需分配。各盡其才、各取所需,讓每一個人都能找到與之相匹配的人,然後發生各種關係。

25、中國創業市場的野蠻發展階段徹底結束了,“硬科技”會成為下一個創業浪潮的新主流。“唯快不敗”的原則可能會慢慢被放棄,我們會呼喚一種“慢哲學”,同時那些“快公司”會面臨考驗。

26、中國行銷業態的進化論:媒介為王——技術為王——內容為王——產品為王。傳統廣告總是依靠媒介的力量去影響人,比如央視的招投標。後來的互聯網廣告開始依靠技術實現精准投放,比如按區域、按收入、按時段投放。再後來社交媒體的崛起使好的廣告能自發傳播,而未來最好的廣告一定產品本身,最好的產品也一定具備廣告效應。

27、中國產業鏈的流向正在逆襲。以前是先生產再消費:生產者——經銷商——消費者。未來一定是先消費再生產:消費者——設計者——生產者。因此,傳統經銷商這個群體將消失,而能夠根據消費者想法而轉化成產品的設計師將大量出現。

28、未來所有的“經銷商”都將變成“服務商”,他們不再依靠幫廠家售賣產品(賺差價)掙錢,而是依靠自己向消費者提供後續的增值服務賺錢,這有利於發揮他們的創造性和主動性,也有利於產品的售後。

國家篇

29、短期內病毒不會迅速消失,會和人類共存,病毒會繼續變種,提高感染率,但降低殺傷力。由於疫苗廣泛注射,2021年3月後疫情應會緩和。

30、中國的產業經濟正在乘上產業智慧革命的列車,通過新硬體革命、新材料革命、大資料革命,形成工業革命和互聯網革命的一次巨大融合,並改造中國社會和企業的每一個細胞。

 

31、2021年,5G商用,將走向成熟。5G新建基站將超過100萬個,過去5G商用最頭疼的“應用場景”,也將在2021年逐步走向成熟。5G+超高清4K/8K視頻,是目前最為明確的應用方向,有望最先迎來爆發,車聯網、智慧電網、VR/AR、智慧城市…5G商用帶來的種種變化,將會超過過去30年的總和。

32、單身經濟,萬億商機。一個孤獨的小人兒遙望地球,這個熟悉的微信介面,正在成為當代許多人的最真實寫照。2.4億人。這是民政部2018年公佈的單身成年人資料,其中有超過7700萬的成年人是獨居。預計到2021年,這一數字會上升到9200萬人。這一趨勢也捎帶手撐起了一個萬億級市場。

33、中國商業本質正從“物以類聚”切換到“人以群分”。這句話有兩層意思:第一,原來社會的中心是“物”(產品、商品),是人隨物動;未來社會的中心是“人”。是物隨人動,以人為本的時代到來。第二,原來社會結構按“物品”歸類,未來社會按“人群”歸類。相同愛好、志向的人很容易彙聚到一起。未來的社會將很有意思,一部分人將完全搞不懂另外一群人,君子和而不同。

34、產業鏈和科技領域,被卡脖子的地方充滿機會。我們被卡脖子的地方,也正是我們要奮力突破的地方!以前可能不明晰發展方向,現在簡直一清二楚。

35、中國經濟正在先裂變後聚變。裂變指的是企業和組織大量斷裂,很多自由職業者被釋放,而同時這些自由個體又在不斷的發生重組,為了共同完成一件大任務,他們揮之則來、來則能戰,靈活、獨立、又可高度協作。可以肯定的是:無論是裂變還是聚變,都可以釋放很大的能量,這就是原子彈和氫彈的基本原理。

36、中國社會的傳統關係網被不斷撕裂,以價值分配為關係、新的連結正在形成,每個人都是一個節點,進行價值傳輸。新的社會架構講究的是“規則”而不是“關係”而你所處的地位和層級,是由你所帶來的價值決定的。
37、中國商業未來十年內的主題都將離不開“跨界互聯”,以互聯網+為基礎,不同行業之間互相滲透、兼併、聯合,從而構成了商業新的上層建築。不同業態將互相制衡,最終達到一種平衡的狀態,從而形成新的商業生態系統。

38、原來中國的基本細胞是“企業”。社會上的每一個“需求”和“供給”往往都是由企業對企業所完成,而今後中國的基本細胞是“個人”。供需雙方很多都在個人化,中國的社會結構將越來越精密細緻。可以做一個這樣的比喻:如果中國經濟是一場血液迴圈,那麼今後它的毛細血管會更加豐富,輸送和供氧能量會更加強大。

39、對於未來每個人來說,有一個東西會變的很重要,那就是信用。行為——信用——能力——人格——財富。在大資料的説明下,你的行為推導出了你的信用值,然後以信用度是支點,能力為杠杆,人格為動力,聯合撬動的力量範圍,就是你所掌控世界的大小。
40、中國商業角逐的核心先後經歷了:地段——流量——粉絲三個階段,房地產經營的就是地段,傳統互聯網經營的就是流量,自媒體經營的是粉絲。以前是沒有調查就沒有發言權,今後是沒有粉絲就沒有發言權。未來就是“影響力”和“號召力”之爭,“核心粉絲”的瞬間聯動是未來商業的“引力波”

41、中國精神文明的紅利期正在到來。傳統的物質文明進展步伐已經開始放慢,因為工業化已經將社會各項硬性設施佈局完善,物質的野蠻增長期已經過去,而互聯網又已經把所有的連結搭建完畢,柔性內容開始兇猛增長,新文化行業是一個增長點。

42、中國進步的根本邏輯是:科技——商業——經濟。科技進步是最根本動力,然後會引發商業重組,進而使社會的經濟體制發生變化。如果我們的商業模式的繁榮不是以科技創新(實體)為基礎,那麼必將引起經濟的泡沫。

43、人與人之間的獨立性在增強,人們更加願意追求內心的幸福;
44、中國的紅利:將從制度紅利、人口紅利,轉入到文化紅利;

45、中國的競爭力:以前靠自然資源,後來靠制度,現在正切換成靠文明;“所有事到最後都會是好事。如果還不是,那它還沒到最後。

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