Pakati pegore ra2017, Merck akazivisa migumisiro inofadza neZVICHOKWADI, chiitiko chinokosha chinodzidza nemishonga yavo yekuongorora, anacetrapib. Anacetrapib yakagadzirirwa kuwedzera HDL cholesterol ("yakanaka" cholesterol). Merck's press release yakataura kuti, kana yakawedzerwa kune statin therapy , anacetrapib yakaderedza zvakanyanya kuitika kwematambudziko emwoyo kune varwere vakanga vari pangozi yakakura yepfungwa yemwoyo .
Chiziviso chakauya sechishamiso chikuru kuvadzidzi vakawanda vemapurisa.
Nei Chiitiko Chisingaiti?
Anacetrapib cholesterol ester kuwedzerwa mapuroteni (CETP) inhibitor, kirasi yemishonga yakanyatsogadzirwa kuti iwedzere ropa re HDL cholesterol. Nokuti huwandu hweHDL cholesterol hwakagara huchibatanidza nehutano hwakakonzerwa nehutano hwemwoyo, nyanzvi dzenguva yakareba dzikatenda kuti zvinodhaka izvo zvakadzivisa CETP zvingave zvakakosha zvikuru kune vanhu vane ngozi yepfungwa yakakwirira.
Saizvozvowo, kubvira kuma1991 makambani akasiyana-siyana emishonga akashandisa mabhiriyoni emadhora achikura nekuedza maverengi eCETP inhibitors. Nyanzvi dzezvepfungwa uye vashandi vezvikwata zvakafanana zvaive zvisingabatanidzi mukufunga kuti zvimwe zvishoma zveCETP inhibitors dzaizova blockbusters.
Hazvina kuitika saizvozvo. Zvechokwadi, kwemakore anoverengeka musati wakazivisa 2017 Merck, CETP inhibitors yakanga yasvika pakuonekwa seimwe yezvinhu zvinodhura zvikuru "mabhasi" mune mishonga yemishonga.
Kunyangwe naMerck's preliminary declaration of success with anacetrapib, nyanzvi dzakawanda dzinoramba dzisina chokwadi kuti CETP inhibitors inowanzoitika, kana anacetrapib kunyanya, ichava nemigumisiro yakawanda muupenyu hwevanhu, kana pane imwe nyanzvi yekambani yezvinodhaka.
Nhoroondo Pfupfupi yeCETP Inhibitor
Kuvhara muchetura weCETP kwakava chinangwa chinokwezva kune vanoita zvinodhaka mumakore ekuma 1990, apo yakadzidzwa kuti mapurisa asina CETP aiva neHDL yepamusoro uye kusagadzikana neatrosclerosis .
Nokukurumidza pashure pacho (kana vatsvakurudzi vakatanga kuvatsvaga), vanhu vazhinji vakaonekwawo avo vakanga vachinjwa mutsika yavo yeCETP iyo yakazobatanidzwa neHDL yepamusoro uye nengozi yakaderedzwa zvikuru yeconary artery disease (CAD) .
Izvo zvairehwa zvakajeka: Kungoshandisa madhiragi anodzivisa CETP, uye iwe uchasimudza mazinga eHDL uye nokudaro unoderedza chirwere chemwoyo. Nekushingaira kukuru uye nemari yakawanda, makambani akawanda emishonga akatanga mapurogiramu makuru kuita izvo chete. Uye pakati pemakore ekuma 2000, kuongororwa kwechipatara nekatenderedzwa yeCETP inhibitors yakatanga, kune fanfare huru uye kuverenga kwechido chekugadzirwa kwekuchi.
Saka kushamisika kwaiva kwechokwadi apo, kwemakore anodarika gumi, zvibereko zvemakiriniki ekuedzwa neCETP inhibitors vaiva (kutaura zvishoma) kuora mwoyo.
Chirwere chekutanga chekukundikana chaiva chetcetrapib (Pfizer), mugore ra2006. MuIlmuminate muedzo, vanhu vanobva pangozi yakawanda vaisarudzwa kuti vawane kana torcetrapib kana placebo (pamwe chete nesitemu). ICETP inhibitor yakaratidza kuita izvo munhu wose aida kuti zviite: vanhu vanowana torcetrapib vaiva ne 72 muzana yehuwandu hweHDL, uye 24 muzana inoderera muLDL cholesterol-saka kuderedzwa kukuru mumatambudziko emwoyo kwakatarisira.
Zvisinei, zvakasiyana zvakaitika. Pakupera kwekudzidza, vanhu vakashandurwa kuti torcetrapib zvirokwazvo vaiva ne25 muzana kuwedzera mumatambudziko emwoyo, uye 58 muzana yevakafa. Pfizer nokukurumidza akasiya torcetrapib.
Nyanzvi dzakaratidza kupararira, kushamisika kushamiswa pamusana uyu wakaipa. Kushamiswa kwakashandurwa pakusiya basa kwemakore anotevera, sezvo mamwe CETP inhibitors ari pasi pekugadzirwa akakundikanawo kugadzirisa migumisiro, pasinei nokuwedzera kuwedzera kukuru muHDL cholesterol.
Muna 2012, Hoffman-La Roche akarega kusimbiswa kweCETP inhibitor, dalcetrapib, apo kuongororwa kwemukati kwekurapa kwavo kukuru kwekliniki kwakaratidza kuti hakuna kliniki inobatsira.
Uye muna 2015 Eri Lilly akadzikisa kukura kwavo kweEvcetrapib, nokuda kwechikonzero chimwe chete.
Pakazosvika gore ra2015, anenge munhu wose aidavira kuti kutevera CETP inhibitors kwakanga kwava mapofu. Zvechokwadi, Merck akafunga kuti achidzivisa chirwere chaVO REVANZI neanacetrapib nenguva iyoyo, asi pakupedzisira akasarudza kuramba achienda.
Pakazosvika Merck yakagadzira chiziviso chaJune, 2017, ndicho chaiva kubudirira kweCETP inhibitor, kwete kukanganisa kwayo, kwakazoita kushamisika.
Chero Nzira, Hapana Munhu Anotofanira Kutariswa
Dai taifanira kunyatsoongorora izvo zvinozivikanwa nezveHDL lipoproteins uye CETP, zviitiko "zvinoshamisa" zvakaonekwa ne-CETP zvakasiyana-siyana inhibitor hazvingashamisi zvakanyanya.
Zvinotarisa kuti zviito zveCETP enzyme zvakaoma kwazvo, uye zvine zvakasiyana-siyana pamusana peHDL cholesterol chete, asi zvakare LDL cholesterol, uye pane zvimwe zvikamu zvehutachiona hwemastabolism. Nokuda kwekuoma uku, hazvikwanisi kutaurirwa mberi kwekuti chii chinogadzirisa kuderedzwa kweCETP enzyme kuchava nemigumisiro yezvipatara. Iko mabhuku anotsvakurudza anonyatsopa huchapupu hwakawanda hwekuti CETP inhibition inogona kuita kuti zvinhu zviwedzere kune mamwe mamiriro ezvinhu.
Somuenzaniso, apo (sezvatakamboona) vamwe vanhu vane ruzivo rwechimiro mumutambo weCETP vane marefu eHDLL uye nengozi yakaderera yehutano hwehutano, zvinoitika kuti vamwe vane mararamiro akasiyana-siyana ekuderedza muCETP vane high HDL levels asi huwandu hwehutano hwechirwere chemoyo. Zvinoratidzika kuti iyo CETP enzyme inogona kukurudzira dzimwe nguva, uye dzimwe nguva kudzivirira kubva, yakakurumidza kushaya atherosclerosis, zvichienderana nehupenyu hwevanhu, maitiro emagetsi, uye pamwe pane zvimwe zvinhu.
Kuenzanisira pfungwa iyi, vatsvakurudzi vanoita sokuti vakaona chikamu chevanhu vanobva kuIlmuminate muedzo uyo aiva nechimwe chimiro chekuberekwa, umo torcetrapib yakagadzirisa mungozi yemwoyo (pasinei nokuti ichi chinodhaka chakaipa zvikuru muhuwandu hwevanhu vakawanda). Zvichida kubudirira kweCETP inhibitor kunoda kusarudzwa kusarudzwa kwevarwere, kushandisa shanduko uye / kana kushandiswa kwemashoko.
Nharo ndeyokuti kubudirira kana kukundikana kweCETP kusagadzikana kwakaoma uye kwakawanda, uye ani zvake anotaura kuti "anoshamiswa" nekugadziriswa kwechipatara nemumwe wemishonga iyi zvichida haanzwisisi kuti zvakaoma sei dambudziko iri riri kuitika.
Inga Anacetrapib Ichashanduka Kuti Ive Chiito Chikuru Here?
Muchiratidzo REVEAL, vanopfuura 30 000 vanhu vane atherosclerotic vascular zvirwere vakange vakagadziriswa kugamuchira vanacetrapib pamwe nepamusoro-dose atorvastatin kana atoravstatin chete. Pashure pemakore mana, pakanga paine kuderedzwa kwe 9% muhutano hwemwoyo kune avo vanotambira anacetrapib. Chigumisiro chakayerwa muchirongwa REVEAL chaive chikamu chekufa kubva kuCAD, kurwisa mwoyo , uye chidimbu chegoni reary revascularization (kureva, kuburikidza nekuvhiya uye / kana stent ). Ikoko kwakanga kusina kuderedzwa pakufa kwevanhu vose, zvakadaro.
Muhurukuro yehurukuro, Merck vakaratidza kuti vacha "funga kana kuisa" kuvhirwa zvinodhaka neCDA. Izvi zvinoratidza kusanganisa hazvishamisi kukambani yezvinodhaka kushandiswa kwemashoko inozivisa kubudirira kwekliniki yekuedzwa. Zvinenge zvichida kubvuma kuti ukuru hwekubatsirwa nevanacetrapib inoratidzika sechepakati, kana uchienzaniswa nezvikwereti zvisingazivikanwi kubva kune nguva refu kwenguva refu nemishonga iyi.
Anacetrapib inochengeterwa kwenguva yakareba mumaawa mashoma, uye saka inoramba iri mumuviri kwenguva refu. Izvi zvingaita kuti zvive zvakanyanya kunetseka kana, zviti, zvisingawanzo asi zvakanyanya kukanganisa zvinozopedzisira zvawanikwa. Ichi ndicho chimwe chinhu icho kambani ichafanira "kufunga" sezvo inosarudza kana ichienda mberi.
Saka zvinoratidzika sezvisinganzwisisiki kuti Merck anotarisira zvinhu zvikuru kubva kune ichi chirwere, uye zvinoratidzika sezvisingabviri kuti anacetrapib ichapedzisira yava blockbuster CETP inhibitor iyo munhu wose aimbofungidzira.
Pari zvino zvinoratidzika kunge zvichida kuti anacetrapib inogona kuve, kana chero chinhu, nhengo inoshanda muhutano hwehutano hwemwoyo.
Shoko Rinobva
Merck chiziviso chekubudirira kwehutano mumakiriniki avo neCETP inhibitor anacetrapib, asi vachikurudzira, inofanira kuonekwa sechitarisiko panguva ino.
Zvichipa nhoroondo inonyadzisa yeimwe CETP inhibitors, zvimwe zvezvisikwa zvechirwere ichi, uye kuti Merck pachayo inoratidzika seisina chokwadi pamusoro pemishonga, hatifaniri kufara zvikuru panguva ino pamusoro pevanacetrapib senzira itsva inokosha yekuderedza moyo wehutano .
> Sources:
> Kosmas CE, DeJesus E, Rosario D, et al. CETP Kurambidza: Kukundikana Kwekare uye Ramangwana Tariro. Clinical Medicine Insights: Cardiology 2016: 10 37-42 ini: 10.4137 / CMC.S32667.
> HPS3-TIMI55-KUVARIDZIRA Gungano Rakabatana. Migumisiro yeAnacetrapib muvarwere vane Atherosclerotic Vascular Disease (REVEAL). N Engl J Med 2017; ini: 10.1056 / HEJMoa170664.