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Mazuva ano, Nonalcoholic fatty chiropa chirwere (NAFLD) yava chikonzero chikuru chechirwere chisingaperi chechiropa muChina uye kunyange munyika. Chirwere ichi chinosanganisira simple hepatic steatohepatitis, nonalcoholic steatohepatitis (NASH) uye inechekuita cirrhosis nekenza yechiropa. NASH inoratidzirwa nekuwanda kwemafuta kuunganidzwa muhepatocytes uye kukonzeresa kukuvara kwemasero uye kuzvimba, ine kana isina hepatic fibrosis. Kuoma kwechiropa fibrosis muvarwere veNASH kunonyatsobatanidzwa nehurombo husina kunaka hwechiropa (cirrhosis uye zvinetso zvayo uye hepatocellular carcinoma), zviitiko zvemwoyo, extrahepatic malignancies, uye zvose-zvinokonzera rufu. NASH inogona kukanganisa hupenyu hwevarwere; zvisinei, hapana mishonga kana marapiro akatenderwa kurapa NASH.

Ongororo ichangoburwa (ENLIVEN) yakabudiswa muNew England Journal of Medicine (NEJM) yakaratidza kuti pegozafermin yakavandudza zvose chiropa fibrosis uye chiropa chinoputika mubiopsy-yakasimbiswa kwete-cirrhotic NASH varwere.

The multicenter, randomized, double-blind, placebo-controlled Phase 2b clinical trial, yakaitwa naProfessor Rohit Loomba nechikwata chake chekiriniki paUniversity of California, San Diego School of Medicine, yakanyoresa varwere mazana maviri nemakumi maviri nevaviri vane biopsie-yakasimbiswa nhanho F2-3 NASH pakati paGunyana 28, 2021 naNyamavhuvhu 15, 2022 vakapihwa majekiseni asina kurongeka. mg kana 30 mg kamwe pavhiki, kana 44 mg kamwe chete mavhiki e2) kana placebo (kamwe pavhiki kana kamwe chete mavhiki e2). Mapeji ekutanga aisanganisira ≥ nhanho 1 kuvandudzwa mufibrosis uye hapana kufambira mberi kweNASH. NASH yakagadziriswa pasina fibrotic kufambira mberi. Chidzidzo chacho chakaitawo ongororo yekuchengeteka.

Mushure memavhiki makumi maviri nemana ekurapwa, chikamu chevarwere vane ≥ danho rekutanga kuvandudzwa kwefibrosis uye pasina kuwedzera kweNASH, uye chikamu chevarwere vane kuderera kweNASH uye pasina kuwedzera kwefibrosis kwaive kwakakwirira zvikuru mumapoka matatu ePegozafermin dose kupfuura muboka re placebo, ine misiyano yakawanda muvarwere vanobatwa ne44 mg kamwe chete pavhiki mbiri kana 30. Panyaya yekuchengeteka, pegozafermin yakanga yakafanana ne placebo. Zviitiko zvakaipisisa zvinosangana nepegozafermin kurapwa kwaiva kusvotwa, manyoka, uye erythema panzvimbo yejekiseni. Muchikamu chino chechipiri chekuedza, migumisiro yekutanga inoratidza kuti kurapwa ne pegozafermin kunovandudza chiropa fibrosis.

pegozafermin, yakashandiswa muchidzidzo ichi, ndeyekureba ichiita glycolated analogue yemunhu fibroblast growth factor 21 (FGF21). FGF21 inonzi endogenous metabolic hormone yakavanzwa nechiropa, iyo inoita basa mukugadzirisa lipid uye glucose metabolism. Zvidzidzo zvekare zvakaratidza kuti FGF21 ine kurapa kwevarwere veNASH nekuwedzera chiropa insulin senitivity, kukurudzira mafuta acid oxidation, uye inhibiting lipogenesis. Nekudaro, iyo pfupi hafu yehupenyu hwezvisikwa FGF21 (anenge maawa maviri) inoganhura kushandiswa kwayo mukurapa kweNASH. pegozafermin inoshandisa glycosylated pegylation tekinoroji kuwedzera hafu yehupenyu hwechisikigo FGF21 uye kukwidziridza kuita kwayo kwebiology.

Mukuwedzera kune migumisiro yakanaka mune iyi Phase 2b kliniki yekuedza, imwe tsvakurudzo ichangobva kuitika yakabudiswa muNature Medicine (ENTRIGUE) yakaratidza kuti pegozafermin yakaderedzawo zvakanyanya triglycerides, isiri-HDL cholesterol, apolipoprotein B, uye hepatic steatosis kune varwere vane hypertriglyceridemia yakaoma, iyo inogona kuva nemigumisiro yakanaka pakuderedza ngozi yemwoyo yeAsh.

Zvidzidzo izvi zvinoratidza kuti pegozafermin, senge endogenous metabolic hormone, inogona kupa akawanda metabolic mabhenefiti kuvarwere vane NASH, kunyanya nekuti NASH inogona kuzopihwa zita rekuti metabolically inobatanidza mafuta echiropa chirwere mune ramangwana. Mhedzisiro iyi inoita kuti uve mushonga wakakosha mukurapa kweNASH. Panguva imwecheteyo, izvi zvakanaka zvekudzidza zvinotsigira pegozafermin muchikamu chechitatu chekiriniki miedzo.

Kunyange zvazvo maviri evhiki nevhiki 44 mg kana vhiki nevhiki 30 mg pegozafermin kurapwa kwakawana histological primary endpoint yekuedza, nguva yekurapa muchidzidzo ichi yaingova masvondo makumi maviri nemana chete, uye chiyero chekuteerera muboka re placebo chaiva 7% chete, iyo yakanga yakaderera zvakanyanya kudarika migumisiro yezvidzidzo zvekare zvekiriniki zvakatora mavhiki makumi mana nemasere. Misiyano nechengeteko zvakafanana here? Tichifunga nezvekusiyana kweNASH, yakakura, yakawanda-pakati, miedzo yekiriniki yepasi rose inodiwa mune ramangwana kuti ibatanidze huwandu hwevarwere uye kuwedzera nguva yekurapa kuti iongorore zvirinani kushanda uye kuchengetedzeka kwemushonga.