Ngomnyaka ka-2017, uMerck wamemezela iziphumo ezilungileyo kunye novavanyo lwazo lwe-REVEAL, iziphumo eziphambili zokufunda kunye neziyobisi zabo zophando, i-anacetrapib. I-Anacetrapib yenzelwe ukwandisa i- HDL ye-cholesterol ("entle" ye-cholesterol). I-Merck's release release yatsho ukuba, xa yongezwa kwonyango lomthetho, i-anacetrapib yanciphisa kakhulu iziganeko zeziganeko zomoya kunye nezigulane ezazisengozini ephezulu yesifo senhliziyo .
Isibhengezo saza sothusa kakhulu kwizinto ezininzi ze-cardiologists.
Kutheni kukhwankqiswa?
I-Anacetrapib i-cholestolol ester transfer protein (CETP) inhibitor, iklasi yezilwanyana ezicwangciswe ngokukodwa ukwenzela ukwandisa kakhulu izinga legazi le-cholesterol ye-HDL. Ngenxa yokuba amazinga e-HDL aphakanyisiweyo aphakanyiswe ixesha elide kunye nokunciphisa ingozi ye-cardiovascular risk, iingcali zide zikholelwa ukuba iziyobisi ezivimbela i-CETP ziya kuba luncedo kakhulu kubantu abanomngcipheko we-cardiovascular risk.
Ngenxa yoko, ukususela ngo-1990 iinkampani ezahlukeneyo zeziyobisi ziye zachitha iibhiliyoni zeedola ezikhulayo kunye nokuvavanya i-CETP inhibitors eziliqela. Iingcali ze-cardiovascular and investors ngokufanayo zaziphantse zidibanise ekucingeni ukuba ubuncinci be-CETP inhibitors babeza kuba yi-blockbusters.
Akuzange kwenzeke ngaloo ndlela. Enyanisweni, iminyaka emininzi ngaphambi kokumenyezelwa kwe-Merck ka-2017, ii-inhibitors ze-CETP ziye zafunyanwa ngehlabathi njengenye yezona "bhasi" ezixabisekileyo kwiimbali zonyango.
Ngaphandle kokubhengezwa kokuqala kweMerck kunye ne-anacetrapib, iingcali ezininzi zihlala zikholelwa ukuba ii-inhibitors ze-CETP ngokubanzi, okanye i-anacetrapib ngokukhethekileyo, ziya kuba nefuthe elihle ebomini babantu, okanye kwiphina inzuzo yenkampani yeziyobisi.
Imbali emfutshane ye-CETP Inhibitors
Ukuvimbela i-enzyme ye-CETP yaba yinto ekhangayo kwizixhobo zonyango ngama-1990, xa yafunyanwa ukuba iinduna ezingenayo i-CETP zinamazinga aphezulu e-HDL kunye nokuxhatshazwa kwe- atherosclerosis .
Kungekudala emva koko (abaphandi baqala ukukhangela), abantu abaninzi babonwa ukuba babeguqulwe kwi-gene ye-CETP eye yahlanganiswa namazinga aphezulu e-HDL kunye nomngcipheko owancitshiswa kakhulu we-coronary disease (CAD) .
Ingqalelo ibonakala: Ukuyila nje iziyobisi ezivimbela i-CETP, kwaye uya kukwandisa amazinga e-HDL kwaye ngoko unciphise isifo senhliziyo. Ngomgudu omkhulu kunye neendleko ezinkulu, iinkampani ezininzi zamachiza zenzile iinkqubo ezinkulu ukwenza oko kanye. Kwaye phakathi kwee-2000, ukuvavanywa kweklinikhi kunye ne-CETP ezinqamlekileyo ezinqamlekileyo, zaqala ukuqhubela phambili, kuba luhlobo olukhulu lweentlobo zezinkukhu kunye nokubala ngokunyanisekileyo kweenkukhu eziphambili.
Ngoko ukumangalisa okwenene xa, kwiminyaka engaphezu kweyishumi, iziphumo zezilingo zekliniki kunye ne-CETP inhibitors (zithi zincinci) zididekile.
Isilwanyana sokuqala siphumelele sasiyi-torcetrapib (Pfizer), ngowama-2006. Kwimeko yesilingo, abantu abavela kwiphepha elibi kakhulu bafumana i-torcetrapib okanye i-placebo (kunye nesimo somfanekiso). I-CETP inhibitor ibonakala yenza oko wonke umntu ayekufuna ukuba akwenze: abantu abafumana i-torcetrapib babe ne-72 kwenyuka kwizinga le-HDL, kwaye ama-24 ekhulwini ayancipha kwi-LDL ye-cholesterol-ukwenzela ukuba kuncitshiswe kakhulu imicimbi ye-cardiovascular.
Nangona kunjalo, kwenzeka okuchasene. Ekupheleni kolu pho nonongo, abantu abanomdla kwi-torcetrapib ngokwenene babe nokwanda kweepesenti ezingama-25 kwimicimbi ye-cardiovascular, kunye nama-58 ekhulwini kunyuka ekufeni. Pfizer ngokukhawuleza yashiya i-torcetrapib.
Iingcali zivakalise ukutshwankqiswa, okumangalisa ngolu hlobo. Ukumangaliswa kuye kwaba ukuyeka emsebenzini kule minyaka elandelayo, njengoko ezinye i-CETP inhibitors phantsi kokuphuhliswa nazo zahluleka ukuphucula iziphumo, nangona zivelisa ukwanda okukhulu kwi-cholesterol ye-HDL.
Ngo-2012, uHoffman-La Roche wayeka ukuphuhliswa kwe-CETP inhibitor yabo, i-dalcetrapib, xa uhlalutyo lwesikhashana lweesilingo lwabo olukhulu lweklinikhi alubonanga inzuzo yeklinikhi.
Kwaye ngo-2015 u-Eli Lilly wayeka ukuphuhliswa kwazo kwe-evacetrapib, ngenxa yesizathu esifanayo.
Ngo-2015, phantse wonke umntu wayekholelwa ukuba ukuphishekela i-CETP inhibitors kuye kwaba yinto engaboniyo. Enyanisweni, uMerck uthathelwa ukuyeka isilingo sawo SOKUQALA nge-anacetrapib ngeli xesha, kodwa ekugqibeleni ukhethwa ukuba aqhubeke.
Ngelo xesha uMerck wenza isimemezelo sakhe ngoJuni, ngo-2017, kwaba yimpumelelo ebonakalayo ye-CETP inhibitor, kungekhona ukusilela kwayo, okwakumangalisa.
Naliphi na Indlela, Akukho Mntu Omele Akumangaliswe
Ukuba siza kujonga ngokukhawuleza oko kwaziwa malunga ne-HDL lipoproteins kunye ne-CETP, iziphumo "ezimangalisa" ezibonwe kunye nee-inhibitors ezahlukeneyo ze-CETP aziyi kuba yinto emangalisayo.
Kuye kwenzeka ukuba izenzo ze-CETP ze-enzyme ziyinkimbinkimbi, kwaye ineempembelelo ezahlukahlukeneyo kungekhona kuphela kwi-cholesterol ye-HDL, kodwa kunye ne-LDL cholesterol, nakweminye imiba ye-lipid metabolism. Ngenxa yolu bunzima, akunakwenzeka ukuqikelelwa ngaphambi kokuba i-impact yothintelo kwi-enzyme ye-CETP iza kuba neziphumo zekliniki. Uphando olwenene lunika ubungqina obuninzi bokuba i-CETP inhibition ingenza izinto zibi ngakumbi phantsi kweemeko ezithile.
Ngokomzekelo, ngelixa (njengoko sibonile) abanye abantu abanomzimba wokunciphisa umgangatho we-CETP banamanqanaba aphezulu e-HDL kunye nomngcipheko omncinci wesifo senhliziyo, kubonakala ukuba abanye abaneendlela ezahlukeneyo zokunciphisa i-genetic kwi-CETP banamazinga aphezulu e-HDL kodwa ubungozi besifo senhliziyo. Kubonakala ukuba i-enzyme ye-CETP ikwazi ukukhuthaza, ngamanye amaxesha ikhusele, i-atherosclerosis ngokukhawuleza, kuxhomekeke kwiprofayili yomntu, kwisimo sayo sokuxilongwa, kwaye mhlawumbi kwezinye iimeko.
Ukubonisa oku kuluhlu, abaphandi babonakala befumene i-subset yabantu abavela kwilingo le-ILLUMINATE abanesimo esithile sezofuzo, apho i-torcetrapib yanciphise ingozi yomzimba (nangona kunjalo ukuba le miphumo ibonakele kwiziphumo kubantu bonke). Mhlawumbi ukusetyenziswa ngokuphumelelayo kwe-CETP inhibitors kuya kufuna ukhetho oluchanekileyo lwezigulane, usebenzisa iprofayile yezofuzo kunye / okanye i-metabolic profiling.
Ingongoma kukuba, impumelelo okanye ukungaphumeleli kwe-CETP inhibition inzima kwaye i-multitifactorial, kwaye nabani na abathi bathi "bayamangalisa" ngeziphumo zekliniki kunye naliphi na lezi ziyobisi mhlawumbi abahluleki ukuqonda ukuba kunzima kangakanani le ngxaki.
Ngaba i-Anacetrapib iyajika ibe ngumsebenzi omkhulu?
KWESIGQUBO SESIFUNDO, abantu abangaphezu kwe-30,000 abanesifo se-atherosclerotic vascular babenomsebenzi wokufumana i-anacetrapib kunye ne-doorvastatin okanye i-atoravstatin kuphela. Emva kweminyaka emine, kukho ukunciphisa u-9% kwingozi yengqondo yomzimba kulabo bafumana i-anacetrapib. Isiphumo esilinganisiwe kwisifundo SOKUPHILA kwakuyinxalenye yokufa kwe-CAD, ukuhlaselwa kwentliziyo , kunye nemfuneko ye-coronary artery revascularization (oko kukuthi, ukuhlinzwa ngokugqithisileyo kunye / okanye isitofu ). Kwakungekho nciphiso ekufeni kwabantu bonke, nangona kunjalo.
Kwi-release release, uMerck ubonise ukuba "baya kuqwalasela ukuba bayayifaka" ukuvunyelwa kweziyobisi kunye ne-FDA. Oku kukhangeleka okuqhelekileyo kuyinto engavumelekanga yenkampani yokukhishwa kwenkampani ekhatywayo yokuvakalisa i-trial clinical trial. Kungenzeka ukuba ukuvuma ukuba ubukhulu benzuzo evela ku-anacetrapib bubonakala buncinci, ubuncinci xa kuthelekiswa nobungozi obungaziwayo obuvela kwiyeza elide elide nalo mhlaza.
I-Anacetrapib igcinwa ixesha elide kwiiseli ezinamafutha, kwaye ngoko ihlala emzimbeni ixesha elide. Oku kungase kube yinto ebalulekileyo xa, nithi, ayiqabile kodwa inetyhefu enkulu ekugqibeleni ifunyenwe. Le nto yinto enye inkampani iya kufuneka 'iqwalasele' njengoko ikhetha ukuba ingaqhubela phambili.
Ngoko kubonakala kungathandabuzeki ukuba uMerck ulindele izinto ezinkulu ezi zilapha, kwaye kubonakala ngathi akunakwenzeka ukuba i-anacetrapib ibe yinto yokugcina inhibitor ye-blockbuster ye-CETP ukuba bonke abantu babelindele.
Okwangoku ngoku kubonakala ngathi kunokwenzeka ukuba i-anacetrapib ibe, ukuba kukho nanye, i-agent ye-niche ekulawuleni ingozi ye-cardiovascular.
ILizwi
Isibhengezo sikaMerck siphumo esiyimpumelelo kwiikliniki kunye ne-CETP inhibitor anacetrapib, ngelixa likhuthaza, kufuneka lithathwe ngokungqalileyo ngeli xesha.
Njengoko iimbali ezidakisayo zenye i-CETP inhibitors, ezinye zezinto ezikhethileyo zezi zixhobo ezithile, kunye nokuba i-Merck ngokwayo ibonakala ingacatshangwanga malunga neziyobisi, asifanele sivuyiswe kakhulu ngeli nqanaba malunga ne-anacetrapib njengendlela ebalulekileyo yokunciphisa ingozi ye-cardiovascular risk .
> Imithombo:
> Kosmas CE, DeJesus E, Rosario D, et al. I-CETP Inhibition: Ukungaphumeleli kwangaphambili kunye neengcinga zexesha elizayo. Ulwaphulo lwezonyango Ulwaphulo: I-cardiology 2016: 10 37-42 i-doi: 10.4137 / CMC.S32667.
> I-HPS3-I-TIMI55-INKCAZELO YOKUBONELELA IQela. Iimpembelelo ze-Anacetrapib kwizigulane ezine-Atherosclerotic Vascular Disease (REVEAL). N Engl J Med 2017; yenze: 10.1056 / HEJMoa170664.