Maphakathi no-2017, uMerck wamemezela imiphumela emihle ngesilingo sabo SOKUPHILA, imiphumela yokucwaninga okubalulekile nomuthi wabo wokuphenya, i-anacetrapib. I-Anacetrapib iklanyelwe ukwandisa i- HDL ye-cholesterol ("okuhle" ama-cholesterol) amazinga. Ukukhululwa kukaMerck kwasho ukuthi, uma kuhlanganiswe ukwelashwa kwesimiso, i-anacetrapib yanciphisa kakhulu izigameko zezenzakalo zenhliziyo ezigulini ezazisengozini enkulu yezinhliziyo .
Lesi simemezelo saba isimanga esikhulu kwabaningi bezinhliziyo.
Kungani Kuthuswe?
I-Anacetrapib i-cholesterol ester yokudlulisa amaprotheni (CETP) inhibitor, isigaba semithi esenzelwe ukwandisa kakhulu amazinga egazi we-cholesterol ye-HDL. Ngenxa yokuthi amazinga e-HDL aphakeme asebenze isikhathi eside ehlotshaniswa nenengozi yesifo senhliziyo, ochwepheshe bekhatsi eside bakholelwa ukuthi izidakamizwa ezivimbela i-CETP ziyoba usizo kakhulu kubantu abanengozi yokuphefumula kwenhliziyo.
Ngakho-ke, kusukela ngo-1990 izinkampanini ezihlukahlukene zezidakamizwa ziye zachitha izigidigidi zamaRandi ezithuthukisa nokuhlola ama-CETP eziningana. Ochwepheshe bezinhliziyo kanye nabalimi-zimali ngokufanayo babecishe babe munye lapho becabanga ukuthi okungenani ama-inhibitors e-CETP ayengaba yi-blockbusters.
Akuzange kwenzeke ngaleyo ndlela. Eqinisweni, iminyaka eminingana ngaphambi kokumemezela kuka-2017 Merck, i-CETP inhibitors yayibheke yonke indawo ngokuthi "ibhasi" ebiza kakhulu emlandweni wezokwelapha.
Ngisho nesimemezelo sokuqala sokuphumelela sikaMerck nge-anacetrapib, ochwepheshe abaningi bahlala beqiniseka ukuthi i-CETP inhibitors ngokujwayelekile, noma i-anacetrapib ikakhulukazi, izoba nomthelela omkhulu ekuphileni kwabantu, noma kunoma iyiphi inzuzo yenkampani yezidakamizwa.
Umlando omfushane we-CETP Inhibitors
Ukuvimbela i-enzyme ye-CETP yaba isikhangiso esihle kubantu abenza izidakamizwa ngawo-1990, lapho kwafundwa ukuthi amagundane asweleka i-CETP anamazinga aphezulu e-HDL futhi aphikisana nokuqina kwesifo somzimba .
Ngokushesha ngemva kwalokhu (lapho abacwaningi beqala ukuwafuna), kwaqhamuka nabantu abaningana abaye bashintsha isakhi sofuzo se-CETP esiye sahlotshaniswa namazinga aphezulu we-HDL kanye nenengozi encishisiwe ye- coronary artery disease (CAD) .
Okushiwo kwacaca: Yenza nje izidakamizwa ezivimbela i-CETP, futhi uzophakamisa amazinga e-HDL ngaleyo ndlela unciphise isifo senhliziyo. Ngomzamo omkhulu futhi ngezindleko ezinkulu, izinkampani eziningana zezidakamizwa zaqala izinhlelo ezinkulu zokwenza kanjalo. Futhi phakathi nawo-2000, ukuhlolwa kwemitholampilo nge-CETP eziningana ezithembisayo zaqala, ngokuzijabulisa okukhulu nokubalwa komdlandla kwezinkukhu ezandulelwe ngaphambili.
Ngakho-ke ukumangala kwakungokoqobo lapho, iminyaka engaphezu kweyishumi, imiphumela yezilingo zomtholampilo nge-CETP inhibitors kwakuyi (ukusho okungenani) edumazayo.
Isidakamizwa sokuqala sokuhluleka kwakuyi-torcetrapib (i-Pfizer), ngo-2006. Esivivinyweni se-ILLUMINATE, abantu abavela engozini enkulu babenabantu abangahle bakwazi ukuthola i-torcetrapib noma i-placebo (kanye nesimiso). I-CETP inhibitor yabonakala yenza konke okufunwa yilowo nalowo muntu: abantu abathola i-torcetrapib babe nokwanda kwamaphesenti angu-72 emazingeni e-HDL, kanti amaphesenti angama-24 ancipha ku-LDL cholesterol-ngakho kuncishiswe kakhulu imicimbi yezinhliziyo.
Nokho, okuphambene kwenzeka. Ekupheleni kwalolu cwaningo, abantu abangenangqondo ekutheni i-torcetrapib empeleni babe nokwanda kwamaphesenti angu-25 ezenzakalweni zenhliziyo, futhi ukukhushulwa kwamaphesenti angu-58 kwanda. Pfizer ngokushesha washiya torcetrapib.
Ochwepheshe baveze isimanga esasakazeke, esimangalisa kulo mphumela omubi. Ukumangala kwaphenduka ukuyeka emsebenzini eminyakeni elandelayo, njengoba ezinye i-CETP inhibitors ekuthuthukisweni nayo yehlulekile ukuthuthukisa imiphumela, naphezu kokukhiqiza ukwanda okukhulu kakhulu kwe-cholesterol ye-HDL.
Ngo-2012, uHoffman-La Roche wayeka ukuthuthukiswa kwe-CETP inhibitor yabo, i-dalcetrapib, lapho ukuhlaziywa okwesikhashana kwesilingo sabo esikhulu somtholampilo kungabonakali inzuzo yomtholampilo.
Futhi ngonyaka ka-2015 u-Eli Lilly wamisa ukuthuthukiswa kwawo kwe-evacetrapib, ngenxa yesizathu esifanayo.
Ngonyaka ka-2015, cishe wonke umuntu wayekholelwa ukuthi ukuphishekela i-CETP inhibitors bekube yi-blindley. Ngempela, uMerck wayecabanga ukuthi wayeka isilingo sabo REVEAL nge-anacetrapib ngaleso sikhathi, kodwa ekugcineni wakhetha ukuqhubeka.
Ngesikhathi uMerck enza isimemezelo sakhe ngoJuni, 2017, kwaba yimpumelelo ebonakalayo ye-CETP inhibitor, hhayi ukuhluleka kwayo, okwakumangalisa.
Noma yiyiphi indlela, Akekho Umuntu Okufanele Ajabule Ngempela
Uma ngabe sihlolisisa ukuthi yini eyaziwayo nge-HDL lipoproteins kanye ne-CETP, imiphumela "emangalisa" ebonwayo ne-CETP ehlukahlukene inhibitors ngeke ibe isimangalo esikhulu.
Kuvela ukuthi izenzo ze-CETP enzyme ziyinkimbinkimbi kakhulu, futhi inezimo ezihlukahlukene ku-HDL kuphela ye-cholesterol ye-HDL, kodwa futhi ne-LDL cholesterol, nakweminye imikhakha ye-lipid metabolism. Ngenxa yalesi siyinkimbinkimbi, akunakwenzeka ukubikezelwa ngaphambi kokuba umphumela wokunciphisa inzyme ye-CETP kuzoba nemiphumela emitholampilo. Imibhalo yocwaningo inikeza ubufakazi obuningi bokuthi ukuvimbela i-CETP kungenza izinto zibi nakakhulu ngaphansi kwezimo ezithile.
Isibonelo, ngenkathi (njengoba sibonile) abanye abantu abanokunciphisa izakhi zofuzo emisebenzini ye-CETP banamazinga aphezulu we-HDL kanye nomngcipheko omncane wezinzwa ze-cardiovascular, okuvela ukuthi abanye abanezinhlobo ezahlukene zokunciphisa izakhi zofuzo ku-CETP banamazinga aphezulu we-HDL kodwa ingozi enkulu yesifo senhliziyo. Kubonakala sengathi i-CETP enzyme ingase ikhuthaze ngezinye izikhathi, futhi ngezinye izikhathi ivikeleke, i-atherosclerosis esheshayo, ngokuya ngesimo somuntu womzimba, esimweni sayo sokuxilonga, futhi mhlawumbe kwezinye izici.
Ukufanekisa leli phuzu, kubonakala sengathi abacwaningi bathole i-subset yabantu abavela esivivinyweni se-ILLUMINATE ababenephrofayili ethile yezakhi zofuzo, okwenzeka kuzo ukuthi i-torcetrapib yanciphise ingozi yenhliziyo (naphezu kokuthi lezi zidakamizwa zibi kakhulu emphakathini). Mhlawumbe ukusetshenziswa okuphumelelayo kwe-CETP inhibitors kuzodinga ukukhethwa ngokucophelela kweziguli, besebenzisa ukuprofiliswa kwezakhi zofuzo kanye / noma okuyisisekelo.
Iphuzu liwukuthi ukuphumelela noma ukuhluleka kwe-CETP ukuvimbela kuyinkimbinkimbi futhi kunezinhlobonhlobo eziningi, futhi noma ubani othi "uyamangala" imiphumela yemitholampilo nanoma iyiphi yalezi zidakamizwa cishe ehluleka ukuqonda ukuthi kunzima kangakanani le nkinga.
Ingabe i-Anacetrapib izophendukela ekubeni yisenzo esikhulu?
Esivivinyweni esibucayi, abantu abangaphezu kuka-30.000 abane-atherosclerotic vascular disease bahlelwe ukuthi bangathola i-anacetrapib plus i-atorvastatin noma i-atoravstatin kuphela. Ngemuva kweminyaka emine, kwaba nokuncipha kwe-9% enengozini yemithwalo yempilo kulabo abathola i-anacetrapib. Umphumela olinganiselwe ekutadisheni kwe-REVEAL kwakuyingxenye yokufa kwe-CAD, ukuhlaselwa yinhliziyo , kanye nesidingo se-coronary artery revascularization (okungukuthi, ukuhlinzeka nge-bypass kanye / noma i- stent ). Kubekho ukunciphisa kokufa kwabantu, kodwa.
Esikhathini sokukhululwa kwezindaba, uMerck ubonise ukuthi "bazocabangela ukuthi ngabe bayayifaka" yini ukugunyazwa kwezidakamizwa ne-FDA. Lokhu kubonakala okungajwayelekile kuyinkampani yokushicilela ikhamphani yezidakamizwa ememezela ukuhlolwa komtholampilo okuphumelelayo. Kungenzeka ukuthi ukuvuma ukuthi ukuphakama kwe-anacetrapib kubonakala sengathi kuncane kakhulu, uma kuqhathaniswa nezingozi ezingaziwa ezivela ekwelapheni isikhathi eside nalo muthi.
I-Anacetrapib igcinwa isikhathi eside emaqenjini amafutha, ngakho-ke ihlala emzimbeni isikhathi eside. Lokhu kungase kubhekane nokukhathazeka okukhulu uma, kuthiwa, ukutholakala okungajwayelekile kodwa okweqile kutholakala ekugcineni. Lesi sici senye inkampani okufanele idingeke ukuba "icabange" njengoba ikhetha ukuthi iqhubeke yini.
Ngakho kubonakala kungabaza ukuthi uMerck ulindele izinto ezinkulu kulo muthi, futhi kubonakala sengathi akunakwenzeka ukuthi i-anacetrapib izokugcina ibe yi-blockbuster ye-CETP inhibitor ukuthi wonke umuntu wayelindele.
Okwamanje kubonakala sengathi kungenzeka ukuthi i-anacetrapib ingaba, uma kukhona, i-niche agent ekulawulweni kwezinengozi zenhliziyo.
Izwi elivela
Isimemezelo sikaMerck somphumela ophumelelayo emtholampilo nge-CETP inhibitor anacetrapib, kuyilapho ekhuthaza, kufanele kuthathwe njengesixhumi ngalesi sikhathi.
Njengoba kunikezwe umlando odumazayo wezinye izinhlayiya ze-CETP, ezinye zezinto eziphawulekayo zalesi sidakamizwa, nokuthi iqiniso lokuthi uMerck ngokwayo ubonakala engacacile ngalesi sidakamizwa, akufanele sijabule kakhulu kuleli phuzu mayelana ne-anacetrapib njengendlela entsha ebalulekile yokunciphisa ingozi yomzimba .
> Imithombo:
> Kosmas CE, DeJesus E, Rosario D, et al. I-CETP Ukuvimbela: Ukungaphumeleli Kwangaphambili Nezithemba Zesikhathi Esizayo. Imithi yokwelapha Imithi: I-Cardiology 2016: 10 37-42 i-doi: 10.4137 / CMC.S32667.
> Iqembu le-HPS3-TIMI55-REVEAL Yokubambisana. Imiphumela ye-Anacetrapib ezigulini ezine-Atherosclerotic Vascular Disease (REVEAL). N Engl J Med 2017; yenzani: 10.1056 / HEJMoa170664.