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bcl-2，wuyishidangxiazuirenaodebadianzhiyi。

xianshiyashengyiyao，qihexinpinzhonglishengkelapian（apg-2575pian）deshangshishenqingjinrizhengshihuodeshouli，youwangchengweiwoguoshougehuopishangshidebcl-2yizhiji。tongyangshihuopi，zhengdatianqingzuijinyeyoudadongzuo，qizizhuyanfadebcl-2yizhijitqb3909pianjielianhuopiliangxianglinchuang，bingqiezaigangjieshudeesmonianhuishang，shoucigongbuleiqilinchuangjieguo，qizaicll/sllhuanzhedehuanjielvda88.9%，qiezhengtianquanxingkekong。

lingwaihaiyoubaijishenzhou，jinnian4yue，qixinyidaibcl-2yizhijisonrotoclax（bgb-11417）xiangweinaikelazhengshifaqile“touduitou”tiaozhan，genjuqianqiyanjiujieguo，sonrotoclaxxianshichuxiangbiweinaikelagengqiangdexiaolihebadianxuanzexing，bingqiehaijuyoukefuchangjiandedaozhiweinaikelanaiyaoxingtubiandeqianli。ciwai，weinaikelamuqianzaiguoneijinhuopiamlyixiangshiyingzheng，ersonrotoclaxzhengzaikaizhansixiangzhucexingshiyan，qiedouyijinrulinchuangⅱqi，shangshizaiji。

buguo，congmuqianlaikan，laiziaiboweideweinaikelarengranshiquanqiuweiyihuopishangshidebcl-2yizhiji，qizai2016nianfdashangshihou，xiaoshoueyiyu2023nianlaidao23yimeiyuan，bingqieweilaihaiyoushangzhangkongjian。juxi，weinaikeladangxiarengchuyukuaisupaomaquandiqi，quanqiuzaiyanlinchuangchaoguo250xiang，yujifengzhixiaoshoujiangzai2026niandadao60yimeiyuan。

图1.国产主要Bcl-2抑制剂代表及进度

erzaijudadeshichangxiaoyingxia，guochanshilizaoyianchaoyongdong，bingqiezhengzaixiangweinaikelafaqimengliegongshi，dangqianchuyasheng、baiji、zhengdatianqingzhiwai，nuochengjianhua、fuxingyiyao、lupengzhiyaodengyejiaruleweilieweikenailadexinglie。

苦等20年，换来“一家独大”

“bcl-2yizhiji”zheizuodumuqiao，aiboweizoudebingburongyi。

juxi，bcl-2shiyizhongyizhixibaodiaowangdedanbai，yu1983nianbeishoucifaxian，zhengshiyouyutadegaobiaoda，caizaojiulezhongliuxibaowanqiangdeshengmingli。yinci，ruguonengyouxiaoyizhibcl-2danbaibiaoda，jiunengyinfazhongliuxibaodediaowang，congerfahuikangaizuoyong。

danzheibingburongyishixian，zheizhuyaoshiyinweibcl-2danbaijiehejiemianhejiehekoudaidoubijiaoda，yincihennantongguoshejixiaofenzilaidadaozuduanjiehedemude，zaijiashangbcl-2badianhaicunzaiyaowushusongdewenti，zheijinyibuzengjialechengyaodenandu。yushi，zaizaoqizhangdajin10niandeshijianli，duoxiangxiangguanyanjiuzuizhongdouyishibaigaozhong。

yizhidao1996nian，shirenyapeiyaowuyanfazongjianfesikcaizhongyuzhaodaolepojuzhidao，tatongguojiangjiehekoudaiqiegechenglianggepianduandefangshi，zhiyaonenggouzhaodaoyumeigepianduanxiangjiehedexiaofenzi，jiunengjiangqijieheqilai。anzhaozheiyisilu，aibowei（2013niancongyapeichaifenchengli）kaishiqianxinzhuanyan，danzhongjianrengranjinglileliangcishibai，zhidao2007nianjiyintaikedejiaru，shuangfanglianheyanfabinghelixuanchuabt-199zheigejiaoweiwanmeidehuahewu，caideyizuizhongchenggongshangshi。

图2.2016-2024H1维奈克拉营收情况（数据来源：艾伯维年报）

zuoweiquanqiushoukuanqieweiyiyikuanbcl-2yizhiji，weinaikelashangshihoubiankaishixunsufangliang，jiashangjinnianshangbannian12.51yimeiyuanshouru，weikenailadangqianzongyingshouyichaoguobaiyimeiyuan，chengweijixiumeile、yibutinizhihou，aiboweidedisandaquantouchanpin。buguo，yuxiumeile、yibutinidangqianxianruzengzhangpingjingbutong，weinaikelarengchuyukuaisushangshengqi。

zheiyifangmianshiyinweiqishiyingzhengguangfan，baokuocll/sll（manxinglinbaxibaobaixuebing）heaml（jixingsuixibaoxingbaixuebing）dengduogexueyeliujibing，zheixiejibinglinchuangxuqiupubianwangsheng，qiedanjiadoujiaogao，henrongyiqiliang；lingyifangmianzeshiyinweiqishoudaodeshichangchongjijiaoxiao，zuoweiquanqiuweiyiyikuanbcl-2yizhiji，weinaikelamuqianhaiyongyoujueduideshichangzhudaoquan。

danweinaikelabingfeiwanmei，dangqianrengrancunzainaiyaoxingheanquanxingwenti。

juxi，zaizhangqisheruweinaikelazhihou，xibaoneibcl-2danbaidebiaodashuipingkenengfashengbianhua，zheihuidaozhikangaixiaoguomingxianjiangdi。lingwai，tubiandebcl-2jiyinyekenengyingxiangweinaikelayubcl-2danbaizhijiandejiehe，congerjiangdiyaowudeyouxiaoxing，bingqiehaihuidailaiyixiliefuzuoyong，baokuoweichangdaofanying、pizhen、zhongxinglixibaojianshao、xuexiaobanjianshao、waizhouxuezhongdeng。

weici，muqianweinaikelazaijiyaoshishianzhaomeizhoujiliangzhubudizengdefangan，tuijianjiliangweidi1zhou20mg qd，di2zhou50mgqd，di 3zhou100mg qd，di4zhou200mg qd，zhidi5zhoujizhihou400mg qd，zhizhijibingjinzhanhuobukenaishou。jibianruci，yiranhuichuxianyanzhongdezhongliurongjiezonghezheng（tls），zi2016nian4yuehuopizhi2021nian10yue，yingguobuliangshijianbaogaoxitong（huangkaxitong）gongshoudao28fenyuweinaikelashiyongyouguandetlsyisiyaopinbuliangfanyingbaogao，qizhongyou7fenweisiwangbaogao。

zheiwuyijihoulaizheliuxialewandaochaochedejihui。

国产猛踩油门

dangqian，zaiyixieremenbadianshang，guoneiyuanbiguowaijiji，shuangkangadcshiruci，bcl-2yizhijiyeshiruci。juinsightshujukuxianshi，guoneimuqiangongyou16kuanzaiyanbcl-2yizhijiyihuopijinrulinchuang，zheiyishuliangyuanchaohaiwai。

erzhisuoyihuirucirezhong，chulexueyeliudangqianhaiweibeimanzudejudalinchuangxuqiuzhiwai，haiyouhenzhongyaodeyidianshiqishangyehuadeduixiannengli，zheizhuyaozhideshibeidayaoqibdhuozhebeishoubinggoudeqianli。

yiguoneimuqianzaibcl-2yizhijijinzhanzuikuaideapg-2575weili，qijiujuyoubeidaebddeqianzhi。zheiyifangmianshiyinweiqiliaoxiaoheanquanxing，juxi，zailianhebtkyizhijiakatinizhiliaocll/sllhuanzheshi，chuzhirenqunzhongdeorrda100%，fufa/nanzhirenqunzhongdeorrdadao97%；erzaianquanxingshang，apg-2575detlsfengxianhezhongxinglixibaojianshaozhengfashengbiliyedougengxiao。

图3.APG-2575适应症情况及临床进展（数据来源：海通国际研报）

lingyifangmianzetixianzaishiyingzhengshang，congmuqianlinchuangjinzhanlaikan，xueyeliusandashiyingzhengcll/sll、mmhemdsdouyouwangbeiapg-2575quanbunaxia，erweinaikelamuqianzaiguoneihuopidezhiyoucll/sllzheiyilingyu。ciwai，apg-2575de4xiangquanqiuzhuceⅲqilinchuangshiyanyezaikuaisutuijin，youwang2026nianzaimeiguodijiaoxinyaoshangshishenqing。

dangran，yongyoudaebddiqidebingbuzhiyouapg-2575，baijishenzhoudesonrotoclaxjinqiyezaifengkuangshangfen。zaigangjieshudeashnianhuishang，baijikoutoubaogaolesonrotoclaxlianhezebutiniyixianzhiliaocllde1/1bqiyanjiushuju：gongyou56lihuanzhejinxinglefanyingpinggu，orrwei100%，erzaisuoyoujiliangzhong，crlvsuizheshijiandetuiyierzengjia，zongticrzhongweishijianwei10.1geyue。shishishang，sonrotoclaxdexianyoushujuzhengzhujianyanzheng，qizaicll、aml、mm、wmhemcldengchangjianshiyingzhengzhongchengweitongleizuijiabcl-2yizhijidekenengxing。

zhideyitideshi，chulesonrotoclax，baijizaibcl-2yizhijilingyuhaiyoubgb-21447，suiranqimuqianzhishizaiⅰqilinchuang，danzailinchuangqianyanjiuzhong，bgb-21447xianshichuxiangjiaosonrotoclaxewaidexiaolihexuanzexing，bingqiehaiyougengzhangdebanshuaiqi。youcikejian，baijishenzhouyijingxingcheng“shuangbaoxian”，zhengjilihandongzheweinaikeladebazhudiwei。

erchuleyashenghebaiji，qitaguochanbcl-2yizhijiyezaimengzhuijindu，muqianjibendoulaidaolelinchuangⅱqi，bingqiedoujubeichengweibest-in-classdeqianli。

birunuochengjianhuadeicp-248，qinenggouyoudaogengzhangdehuanjiechixushijian，bingyouwangkefuxianyoubcl-2yizhijidenaiyaoxingwenti；youbirulupengzhiyaodelp-108，qiduijiwangjingbtkyizhijizhiliaoshibaider/rcll/sllhuanzhedeorrdadaole70%，erqiezaimeiriyicikuaisudejiliangdaorumoshixia，weiguanchadaotls；lingwaihaiyouzhengdatianqingdetqb3909，qizaicll/sllhuanzhedehuanjielvda88.9%，37.5%deb-nhlhuanzhehuodehuanjie，qiezhengtianquanxingkekong；zuihoushifuxingyiyaodefcn-338，qilianheazhabaoganhuohualiaozhiliaosuixiexingxueyejibingdeyanjiuyichuyuiiqilinchuang，bingqiehaiyouduoxianglinchuangyeyijinruguanjianjieduan。

bunankanchu，guochanbcl-2yizhijidangqiandouzaijiasuzhuangxian，weilieweinaikeladetaishiyijingyufaxiongmeng。erzheiyeyiweizheyichangdazhanyijingzaisuonanmian，wulunshiduiyuweinaikeladezhijiechongji，haishiguochanbcl-2yizhijizhijiandeanzijiaojing，doujianghenkuaishangyan。

野心不止于此

congshiyingzhenglaikan，bcl-2yizhijizhuyaoyingyongyuxueyeliu，eryouyuqigaofaxingyugaoexingtedian，xiangguanyaowushichangguimojiweipangda。genjubeizhesizixunshuju，2024nianquanqiuxueyeexingzhongliuzhiliaoyaowushichangguimoda400yimeiyuan，yujizai2024-2029nianyuceqineicagrzengzhangda6%。

图4.目前全球已获批上市的6款BTK抑制剂情况

juxi，zaibaxiangyaochuxianzhiqian，hualiaoshizhiliaoxueyeliudebiaozhunliaofa，zhidao2013niandiyikuanbtkyizhijiyibutinidedansheng，xueyeliudezhiliaogejucaifashenggenbenxinggaibian。erzaizheizhihou，asilikangdeaketinihebaijishenzhoudezebutinidengduokuanbtkyizhijixiangjihuopishangshi，bingyigenghaodeliaoxiaohegengwendingdeanquanxing，zhubutidaihualiaozuoweixueyeliuhuanzhedezuiyouxuanze。

buguo，btkyizhijirengranyoujuxianxing。juyeneirenshitoulu，wulunnazhongbtkyizhiji，suizhechixuzhiliaodeyakelongdejinhuahexuanze，qidouyouhendakenenghuidaozhijibingfufaheduizheixieyaowudenaiyaoxing。yinci，jixuzhaodaoyizhongkeyidulihuolianhejiejuebtkyizhiji“zhiliaosijiao“dexinxingyaowu。ganghao，bcl-2yizhijijiukeyizuodaozheiyidian。

图5.BTK信号传导通路（图源：制药在线）

jutieryan，xiangbiyudanyao，bcl-2yubtklianheyongyaozaitigaoliaoxiaohejianshaonaiyaodengfangmiandougengyouyoushi：btkikeyishicllxibaoconglinbajietuoluo，ranhouyoubcl-2yizhijiyoudaoxunhuanxitongzhongdezhongliuxibaodiaowang，zheijiuxiangdangyuyibianzaijizhongliuxibaozengzhi“caichache”，yibianyouzaiweiqidiaowang“hongyoumen”。

zhengshijiyuci，zheizhonglianheliaofazhengzaichengweixueyeliuzhangqizhiliaodeyixianbiaozhun。juxi，muqiannenggoutongguoqixiayaowuduliwanchenglianheliaofadeqiyezhiyousanjia，fenbieshiaibowei、baijishenzhouhenuochengjianhua，zheisanjiadouyongyoushuyuzijidebtkyizhijiyubcl-2yizhiji。yiaiboweiweili，qimuqianjinzhanzuikuai，yinweiyongyouweiyiyikuanhuopishangshidebcl-2yizhiji，qiyilvxianzhichengyibutiniwanchenglediyixianglianyongshangshi：2022nian8yue，oumengweiyuanhuipizhunkuodayibutiniyuweinaikelalianheyixianzhiliaocllchengrenhuanzhe。

jinsuiqihoudeshibaijishenzhou，deyiyuzebutinizai2022nian“touduitou”jibaiyibutini，zaijiashangsonrotoclaxjiaoweinaikelayouyouyaoxiaoshangdeyoushi，yincibeikanzuoshiaiboweidezuiyoulijingzhengzhe。zuihoushinuochengjianhua，qigangganggongbulebtkyizhijiaobutinizaizhiliaomzldelinchuangshuju，12liruzuhuanzhezhongyou6liwanchenglezhongqiliaoxiaopinggu，orrwei100%，3lihuanzhewanchenglelianhezhiliaobingjinruweichijieduan，orrtongyangbaochi100%。

erconggexiangshujulaikan，aibowei、baijihenuochengdangqianyijingxingchenglesanzudinglizhishi。neime，duiyuzishenhaimeiyoubtkyizhijideyaoqilaishuo，yougairuhepojuni？daanshiyaozhaodaoshiheyuzishendeqiangliduiyou。

yiyashengweili，suiranapg-2575shiguoneijinzhanzuikuaidebcl-2yizhiji，dankuyuzishenmeiyoubtkyizhiji，yashengzaixueyeliudejingzhengzhongrengranchuyulieshi，zheishiyinweiapg-2575deduishoubingfeibcl-2yizhijidanyao，ershibtkyizhiji+bcl-2yizhijidelianheyongyao。weici，zaozai2020nian6yue，yashengjiuyuasilikangjianlilehezuoguanxi，shuangfangjianggongtongtansuoapg-2575lianheakatinidelinchuangshiyan。muqian，gaishiyanyiyujinnian4yuekaiqilesuijiⅲqiyanzhengxingyanjiu。

buguo，zaizhongduoyeneirenshikanlai，zheibingbushiyashengdezuiyouxuanze，zheishiyinweililaiqixiadedisandaibtkyizhijibituobulutiniyongyougenghaodeliaoxiao，zuoweifdapizhundeshougeqieweiyiyikuanfeigongjia（keni）btkyizhiji，qibanshuaiqiyushengwuliyongdudouxianzhutigao，erzheidoukeyirangyashengapg-2575genghaojieli。zaijiashanglilaiqixiamuqianhaimeiyoujiaoweichengshudebcl-2yaowu，shuangfanghezuodekenengxingdazeng。

dangran，zheidouxuyaoshijianlaiyanzheng。danwulunzenyang，btkyizhiji+bcl-2yizhijilianheyongyaodefangshiyidingshiweilaixueyeliuzhiliaodeshouxuan，jiliejingzhengyejiangyoucilakai。erbcl-2yizhijizuoweizuiqiangfuzhu，tadezhanlveyiyiyebujinjinshigongxianyingshou，tongshihaikeyiwenguqiyezishenzaibtkyaowushichangdediwei。jiubiruaibowei，suiranyibutinishoudaoleshichangchongji，danyuweinaikeladejiehe，youshiqihuanfaxianji，zhongxinzhanzailejingzhengmiandeyouliweizhi。

zheiwuyishiyigedaqushi，erweilaisheinengshengchu，yidingshizaidadaogenggaoliaoxiaodetongshi，younengbaochiwendingdeanquanxing。zheichang“dazhan”jijiangdaxiang，aiboweimuqianyouyidingdexianfayoushi，danyiyashenghebaijiweidaibiaodeguochanyezaifengkuangzhuiji。