iindaba

Namhlanje, isifo sesibindi esinamafutha e-Nonalcoholic (NAFLD) siye saba yimbangela ephambili yesifo esingapheliyo sesibindi e-China nakwihlabathi. Uluhlu lwesifo lubandakanya i-hepatic steatohepatitis elula, i-nonalcoholic steatohepatitis (NASH) kunye ne-cirrhosis enxulumene nomhlaza wesibindi. I-NASH ibonakaliswe kukuqokelelwa kwamafutha amaninzi kwi-hepatocytes kunye nomonakalo weselula kunye nokuvuvukala, kunye okanye ngaphandle kwe-hepatic fibrosis. Ubunzima be-fibrosis yesibindi kwizigulane ze-NASH zidibaniswe ngokusondeleyo ne-prognosis embi yesibindi (i-cirrhosis kunye neengxaki zayo kunye ne-hepatocellular carcinoma), iziganeko ze-cardiovascular, i-extrahepatic malignancies, kunye nokufa konke. I-NASH inokuchaphazela kakubi umgangatho wobomi bezigulane; nangona kunjalo, akukho ziyobisi okanye unyango oluvunyiweyo ukunyanga i-NASH.

Uphononongo olutshanje (ENLIVEN) olupapashwe kwiNew England Journal of Medicine (NEJM) lubonise ukuba i-pegozafermin iphucule i-fibrosis yesibindi kunye nokuvuvukala kwesibindi kwi-biopsy-confirmed non-cirrhotic NASH izigulane.

I-multicenter, i-randomized, i-double-blind-blind, i-placebo-controlled Phase 2b yovavanyo lwekliniki, oluqhutywe nguNjingalwazi uRohit Loomba kunye neqela lakhe lekliniki kwiYunivesithi yaseCalifornia, iSan Diego School of Medicine, ibhalise izigulane ze-222 ezine-biopsie-confirmed stage F2-3 NASH phakathi kwe-28 Septemba, i-2021 kunye ne-15 ka-Agasti, i-2022 yabelwa i-pecuza i-injection, i-2022 i-pecuza i-injection engahleliwe. mg okanye i-30 mg kanye ngeveki, okanye i-44 mg kanye kwiiveki ze-2) okanye i-placebo (kanye ngeveki okanye kanye kwiiveki ze-2). Iziphelo eziphambili zibandakanya ≥ isigaba se-1 sokuphucula kwi-fibrosis kwaye akukho nkqubela ye-NASH. I-NASH isonjululwe ngaphandle kokuqhubela phambili kwe-fibrotic. Uphononongo lwenze novavanyo lokhuseleko.

Emva kweeveki ezingama-24 zonyango, umyinge wezigulane ezine-≥ isigaba soku-1 sokuphucula kwi-fibrosis kwaye akukho mandundu e-NASH, kunye nenani lezigulana ezinokuhlehliswa kwe-NASH kwaye kungabikho kunyuka kwe-fibrosis kwakuphezulu kakhulu kumaqela amathathu edosi ye-Pegozafermin kuneqela le-placebo, kunye nokwahlukana okubaluleke kakhulu kwizigulane eziphathwa nge-44 mg kanye ngeveki ezimbini okanye iiveki ezintathu. Ngokokhuseleko, i-pegozafermin yayifana ne-placebo. Ezona ziganeko zibi zixhaphakileyo ezinxulumene nonyango lwe-pegozafermin yayisisicaphucaphu, urhudo, kunye ne-erythema kwindawo yokutofa. Kulo vavanyo lwesigaba se-2b, iziphumo zokuqala zibonisa ukuba unyango nge-pegozafermin luphucula i-fibrosis yesibindi.

I-pegozafermin, esetyenziswe kolu phando, i-analogue ye-glycolated yexesha elide ye-fibroblast factor growth factor 21 (FGF21). I-FGF21 yihomoni ye-metabolism engapheliyo ekhutshwe sisibindi, edlala indima ekulawuleni i-lipid kunye ne-glucose metabolism. Uphononongo lwangaphambili lubonise ukuba i-FGF21 ineempembelelo zonyango kwizigulane ze-NASH ngokunyusa uvakalelo lwe-insulin yesibindi, ukuvuselela i-fatty acid oxidation, kunye nokuvimbela i-lipogenesis. Nangona kunjalo, i-half-life short-life ye-FGF21 yendalo (malunga neeyure ze-2) iyanciphisa ukusetyenziswa kwayo kunyango lwe-NASH. I-pegozafermin isebenzisa itekhnoloji ye-glycosylated pegylation ukwandisa isiqingatha sobomi bendalo ye-FGF21 kwaye yandise umsebenzi wayo webhayoloji.

Ukongeza kwiziphumo ezilungileyo kwesi Sigaba se-2b solingo lwekliniki, olunye uphando olupapashwe kwi-Nature Medicine (ENTRIGUE) lubonise ukuba i-pegozafermin iphinde yanciphisa kakhulu i-triglycerides, i-cholesterol engeyona i-HDL, i-apolipoprotein B, kunye ne-hepatic steatosis kwizigulane ezine-hypertriglyceridemia enzima, enokuthi ibe nefuthe elihle ekunciphiseni umngcipheko we-cardiovascular events kwizigulane ezine-NASH .

Olu phononongo lucebisa ukuba i-pegozafermin, njengehomoni ye-metabolic engapheliyo, inokubonelela ngeenzuzo ezininzi zemetabolism kwizigulana ezine-NASH, ngakumbi kuba i-NASH inokuphinda ithiywe isifo sesibindi esinxulumene ne-metabolic kwixa elizayo. Ezi ziphumo zenza ukuba libe lichiza elibaluleke kakhulu elinokubakho kunyango lwe-NASH. Kwangaxeshanye, ezi ziphumo zophononongo ezintle ziya kuxhasa i-pegozafermin kwisigaba sesi-3 solingo lwezonyango.

Nangona zombini iiveki ngee-44 mg okanye ngeveki i-30 mg ye-pegozafermin unyango iphumelele isiphelo se-histological primary yolingo, ubude bonyango kolu phononongo yayiziiveki ezingama-24 kuphela, kwaye izinga lokuthotyelwa kwiqela le-placebo laliyi-7% kuphela, eyayiphantsi kakhulu kuneziphumo zezifundo zeklinikhi zangaphambili ezithatha iiveki ze-48. Ngaba iiyantlukwano kunye nokhuseleko ziyafana? Ngenxa yokungafani kwe-NASH, amakhulu, amaziko amaninzi, ulingo lwezonyango lwamazwe ngamazwe luyafuneka kwixesha elizayo ukuze luquke abantu abaninzi bezigulane kunye nokwandisa ixesha lonyango ukuze kuhlolwe ngcono ukusebenza kunye nokhuseleko lwechiza.