A tsakiyar shekara ta 2017, Merck ya sanar da sakamako mai kyau tare da jarrabawar REVEAL, bincike mai mahimmanci tare da kwayoyin bincike, anacetrapib. An tsara Anacetrapib domin ƙara yawan cholesterol na HDL ("good" cholesterol). Jagoran jaridar Merck ya bayyana cewa, lokacin da aka kara wa likita , anacetrapib yana rage yawan abin da ke faruwa a cikin marasa lafiya da ke fama da cutar zuciya .
Sanarwar ta zama babban abin mamaki ga yawancin masu kwakwalwa.
Me yasa mamaki?
Anacetrapib shi ne mai ƙwayar ƙwayar ƙwayar ester transfer (CETP), wata magungunan ƙwayoyi waɗanda aka tsara musamman don ƙara yawan jini na HDL cholesterol. Saboda yawan halayen cholesterol na HDL sun kasance suna haɗuwa da rageccen cututtukan zuciya, masana sunyi imani da cewa kwayoyi da suka hana CETP zasu tabbatar da amfani sosai a cikin mutanen da cutar ƙwayar cutar ta kamu.
A sakamakon haka, tun shekara ta 1990, wasu kamfanonin miyagun ƙwayoyi sun kashe biliyoyin daloli na cigaba da gwada yawan masu hanawa CETP. Masana binciken jijiyoyin zuciya da masu zuba jarurruka sun kasance gaba daya a cikin tunanin cewa a kalla wasu masu hana CETP zasu zama blockbusters.
Ba'a canza wannan hanya ba. A gaskiya ma, shekaru da yawa kafin sanarwar Merck ta shekara ta 2017, an hana masu hana kwastan CETP a matsayin ɗaya daga cikin "busts" mafi tsada a cikin tarihin magunguna.
Ko da tare da sanarwar farko da nasarar da Merck ya yi tare da anacetrapib, yawancin masana sun kasance masu shakka cewa masu hana CETP a general, ko anacetrapib musamman, zasu sami tasiri sosai akan rayuwar mutane, ko kuma dukiyar da ake amfani da magunguna.
Tarihin Brief na Masu CETP
Tsayar da ƙwaƙwalwar CETP enzyme ya zama kyakkyawan manufa ga masu yin magunguna a shekarun 1990, lokacin da aka koyi cewa sandan da ba su da CETP suna da matakan HDL da juriya a atherosclerosis .
Ba da daɗewa ba (da zarar masu bincike suka fara neman su), an gano mutane da yawa wadanda suke da maye gurbin su a cikin sigininsu na CETP wadanda suka kasance sun haɗu da matakan high HDL da kuma rage hadarin cututtukan cututtuka (CAD) .
Abinda ya faru shine bayyane: Kawai tsara kwayoyi da ke hana CETP, kuma za ku inganta matakan HDL kuma ta rage cututtukan zuciya. Da} o} ari da kuma kashe ku] a] e, yawancin kamfanonin miyagun ƙwayoyi sun kaddamar da manyan shirye-shirye don yin hakan. Kuma daga tsakiyar 2000, jarrabawar asibiti tare da wasu masu cin zarafi na CETP sun fara, don yin kyan gani da kuma ƙididdigar ƙwaƙwalwar kaji.
Saboda haka abin mamaki shine ainihin lokacin da, har tsawon shekaru goma, sakamakon gwaji na gwaji tare da masu zanga-zangar CETP sun kasance (ba a ce) ba.
Na farko magani don kasa shi ne torcetrapib (Pfizer), a 2006. A cikin gwaji ILLUMINATE, mutane daga wani yawan mutane masu yawan hadarin sun kasance randomized don samun ko dai torcetrapib ko placebo (tare da statin). Mai haɓaka CETP ya yi kamar abin da kowa yake so ya yi: mutane suna karbar torcetrapib suna da kashi 72 bisa dari a cikin matakan HDL, kuma kashi 24 cikin dari a cikin LDL cholesterol - saboda haka ana tsammanin babban raguwa a cikin abubuwan da ke ciki na zuciya.
Duk da haka, kishiyar ya faru. A ƙarshen binciken, mutanen da aka bazu zuwa torcetrapib suna da karuwar kashi 25 cikin cututtuka na zuciya, da kuma kashi 58 cikin dari na mutuwar. Pfizer da sauri watsi torcetrapib.
Masana sun bayyana yaduwa, mamakin mamaki a sakamakon wannan mummunar sakamako. Abin mamaki ya juya zuwa murabus a cikin shekaru masu zuwa, kamar yadda wasu masu hana CETP a karkashin ci gaba sun kasa inganta sakamakon, duk da samar da ƙananan karuwa a cikin HDL cholesterol.
A 2012, Hoffman-La Roche ya dakatar da ci gaba da ƙwaƙwalwar CETP, dalcetrapib, lokacin da bincike na lokaci-lokaci na babban jarrabawar jarrabawar ya nuna ba amfanin asibiti.
Kuma a 2015 Eli Lilly ya dakatar da ci gaba da evacetrapib, saboda wannan dalili.
By 2015, kusan dukkanin mutane sun yi imanin cewa biyan masu hana CETP ya zama makafi. Lalle ne, Merck yayi la'akari da dakatar da jarrabawar REVEAL tare da anacetrapib a wannan lokacin, amma a karshe aka zaba ya ci gaba.
A lokacin da Merck ya yi Yuni, sanarwar 2017, shi ne bayyanar nasara ta mai hana CETP, ba ta rashin nasara ba, wanda ya zama mamaki.
Ko ta yaya, Babu wanda ya kamata ya firgita
Idan za mu dubi abin da aka sani game da HDL lipoproteins da CETP, abubuwan da "abin mamaki" da aka gani tare da masu cin zarafi na CETP ba zai zama mamaki ba.
Ya nuna cewa ayyuka na CETP enzyme suna da tasiri sosai, kuma yana da tasiri masu yawa a kan ba kawai HDL cholesterol, amma kuma LDL cholesterol, da kuma a wasu al'amurran da lipid metabolism. Saboda wannan ƙwarewar, ba za a iya hango gaba ba game da yadda za a rage a cikin CETP enzyme zai sami sakamako na asibiti. Binciken da aka gudanar na bincike ya ba da cikakken shaidar cewa ƙin CETP zai iya yin mummunan rauni a wasu yanayi.
Alal misali, yayin da (kamar yadda muka lura) wasu mutane da raguwa a cikin aikin CETP suna da matakan high HDL da kuma rashin lafiyar cututtuka na zuciya, yana nuna cewa wasu waɗanda suke da nau'in ƙwayar halitta a CETP suna da matakan HDL amma kara yawan cutar cututtukan zuciya. Ya bayyana cewa ƙwaƙwalwar CETP a wani lokaci yakan inganta, kuma wani lokacin kare daga, inganta atherosclerosis, dangane da bayanin mutum akan labaran su, da kuma yiwuwar wasu dalilai.
Don kwatanta wannan batu, masu binciken sun bayyana alamun mutane daga jarrabawar ILLUMINATE wanda ke da wani nau'i na kwayoyin halitta, wanda a cikin shi ne torcetrapib ya rage yawan cututtukan zuciya (duk da cewa cewa wannan maganin ya kara karuwa a cikin yawan jama'a). Mai yiwuwa yin amfani da masu amfani da CETP na cin nasara zai buƙaci zaɓi mai kyau na marasa lafiya, ta hanyar amfani da kwayoyin halitta da / ko na zamani.
Ma'anar ita ce, nasara ko rashin cin nasara na CETP yana da rikicewa da haɓaka, kuma duk wanda yayi ikirarin "mamaki" da sakamakon magunguna tare da wasu daga cikin wadannan kwayoyi bazai fahimci yadda rikitarwa wannan matsala ta juya ba.
Shin Anacetrapib zai juya ya zama babban babban aiki?
A cikin jarrabawar REVEAL, fiye da mutane dubu 30.000 da ke dauke da cututtuka na asibiti da ke dauke da kwayar cutar ba su da mahimmanci don samun kocetrapib tare da atorvastatin ko atoravstatin kadai. Bayan shekaru hudu, an sami raunin kashi 9% na hadarin zuciya na zuciya a cikin wadanda ke karɓar anacetrapib. Sakamakon da aka yi a cikin binciken REVEAL wani abu ne na mutuwa daga CAD, ciwon zuciya , da kuma buƙata don sake juyayin maganin jini (wato, kewayar tiyata da / ko wani sutura ). Babu rage yawan mace-mace, duk da haka.
A cikin sakin watsa labarai, Merck ya nuna cewa za su "yi la'akari da cewa za su rubuta" don amincewa da miyagun ƙwayoyi tare da FDA. Wannan ƙwararrakin bayyanar abu ne mai ban sha'awa ga sanarwar watsa labaran kamfanin likitancin sanar da ci gaba da gwaji. Wataƙila wata sanarwa tacit cewa ƙarfin amfani da anacetrapib ya nuna kadan kaɗan, akalla idan aka kwatanta da rashin hadari daga maganin wannan magani.
An ajiye Anacetrapib na tsawon lokaci a cikin kitsoyin mai, kuma ya kasance cikin jiki na dogon lokaci. Wannan zai iya zama babban damuwa idan, ya ce, ba a iya ganewa ba amma mai tsanani ne. Wannan matsala shi ne abin da kamfanin zai yi "la'akari" yayin da yake yanke shawara ko ya ci gaba.
Saboda haka yana da alama cewa Merck yana buƙatar babban abu daga wannan magani, kuma yana da alama mai yiwuwa ba zai iya zama anacetrapib ba wanda zai iya zama mai hana shi wanda ya sa kowa ya sa ransa.
Yanzu dai yana da alama cewa anacetrapib zai iya zama, idan wani abu, wakili ne a cikin kula da cututtukan zuciya.
Kalma Daga
Bayanin Merck na samun nasarar nasara a cikin asibiti tare da mai kwantar da hankalin CETP anacetrapib, yayin karfafawa, ya kamata a yi la'akari da shi a wannan lokaci.
Bisa labarin tarihin wasu masu hana CETP, wasu daga cikin maganganun wannan magani, da Gaskiyar cewa Merck kanta ba shi da tabbacin game da miyagun ƙwayoyi, kada mu kasance mai farin cikin wannan batun game da anacetrapib a matsayin hanya mai mahimmanci don rage cututtukan zuciya .
> Sources:
> Kosmas CE, DeJesus E, Rosario D, et al. An haramta CETP: Kasawar da ta gabata da Makomar Layi. Ƙwararren maganin ƙwayar cuta: Kwayoyin cuta 2016: 10 37-42 a: 10.4137 / CMC.S32667.
> HPS3-TIMI55-REVEAL Group Collaborative Group. Ayyukan Anacetrapib a cikin marasa lafiya da cututtukan cututtuka na asherosclerotic (REVEAL). N Engl J Med 2017; Doi: 10.1056 / HEJMoa170664.