EU Pom Zoo Imcivree (setmelanotide): Rov Tsim Kho Kev Siv Hluav Taws Xob thiab txo qhov hnyav!

Raws li cov ntaub ntawv tshiab kawg los ntawm EU daim ntawv pom zoo tshuaj tshiab, Rhythm Pharmaceuticals' tshuaj Imcivree (setmelanotide) rau kev kho mob uas tsis tshua muaj rog tau pom zoo los ntawm European Commission (EC): nws tau siv rau kev kho mob rog thiab tswj kev tshaib plab hauv menyuam yaus thiab cov neeg laus uas tsis tshua muaj rog dhau hnub nyoog ≥6 xyoo. Tshwj xeeb: Cov neeg mob rog tau lees paub los ntawm kev sim ua los ntawm pro-opioid melanocytic corticosteroid (POMC), proprotein convertase subtilisin/kexin1 yam (PCSK1) lossis leptin receptor (LEPR) tsis txaus. Hauv Tebchaws Meskas, Imcivree tau pom zoo thaum lub Kaum Ib Hlis 2020, nrog rau cov lus qhia zoo ib yam li saum toj no.

Nws tsim nyog hais tias Imcivree yog thawj cov tshuaj pom zoo rau kev kho mob ntawm cov noob caj noob ces uas tsis tshua muaj rog. Hauv Tebchaws Meskas thiab European Union, setmelanotide tau txais Orphan Drug Designation (ODD) rau kev kho mob ntawm POMC thiab LEPR-tsis muaj rog, thiab tau txais Kev Txom Nyem Tsim Kev Tsim Tshuaj (BTD) thiab Kev Tsim Tshuaj Ua Ntej Ua Ntej (PRIME) feem. Raws li cov ntaub ntawv los ntawm EU Cov Tshuaj Tshiab Database, Imcivree yuav muaj 10-xyoo kev lag luam tshwj xeeb rau POMC-tsis muaj rog thiab LEPR-tsis muaj rog, txij lub Xya Hli 19, 2021 txog rau Lub Xya Hli 19, 2031.

POMC, PCSK1, lossis LEPR tsis muaj rog yog ib yam kab mob uas tsis tshua muaj tshwm sim los ntawm kev hloov pauv hauv POMC, PCSK1, lossis LEPR noob. Cov kev hloov pauv caj ces no ua rau melanocortin 4 (MC4) txoj hauv kev txais tau, thiab MC4 txoj kev txais tos yog hypothalamus Txoj hauv kev uas tswj hwm kev tshaib kev nqhis, siv lub zog thiab lub cev hnyav. Cov neeg mob rog rog nrog POMC, PCSK1 lossis LEPR tsis muaj peev xwm pib tawm tsam nrog kev tshaib kev nqhis heev thiab tsis txaus ntseeg los ntawm cov menyuam yaus thaum ntxov, ua rau pib ntxov thiab rog hnyav.

Cov tshuaj muaj tshuaj nquag ntawm Imcivree yog setmelanotide, uas yog tus pib ua haujlwm, oligopeptide MC4 receptor agonist tsim los rov ua haujlwm ntawm MC4 tus neeg txais kev puas tsuaj los ntawm cov noob caj noob ces tsis zoo ntawm MC receptor, yog li ncaj qha daws lub hauv paus ntawm tus kab mob vim li cas. Setmelanotide tuaj yeem rov tsim kho tus neeg mob' kev siv lub zog thiab tswj kev qab los noj mov, txo kev tshaib plab, thiab txo qhov hnyav.

Hauv theem 3 kev sim tshuaj kho mob, 80% thiab 45.5% ntawm cov neeg rog rog los ntawm POMC lossis PCSK1 tsis txaus thiab LEPR tsis txaus, feem, poob ntau dua 10% ntawm lawv qhov hnyav tom qab tau txais Imcivree rau ib xyoos.

Setmelanotide mechanism of action

Hauv European Union, Imcivree' kev pom zoo yog ua raws cov txiaj ntsig ntawm ob qhov tseem ceeb Phase 3 kev sim tshuaj. Ob txoj kev tshawb fawb no tau txheeb xyuas qhov ua tau zoo thiab nyab xeeb ntawm setmelanotide hauv kev kho mob POMC (suav nrog PCSK1) -deficient rog thiab LEPR tsis muaj rog. Ob txoj kev tshawb fawb tau mus txog qhov kawg qhov kawg thiab txhua qhov kawg ntawm qhov tseem ceeb thib ob. Cov ntaub ntawv qhia pom tias kev kho nrog setmelanotide ua rau muaj kev txheeb cais tseem ceeb thiab hauv tsev kho mob txo qis hauv lub cev hnyav thiab tshaib plab heev (hyperappetite). Qhov tseem ceeb, thaum lub sijhawm tshem tawm cov tshuaj (8 lub lis piam), qhov hnyav thiab kev tshaib kev nqhis ntawm cov neeg mob tau nce ntau, thiab tom qab rov pib kho, feem ntau cov neeg mob rov qab yuag poob thiab tshaib plab teb. Cov ntaub ntawv no lees paub setmelanotide Nws tuaj yeem pab rov ua haujlwm ntawm MC4R txoj hauv kev tswj hwm lub cev qhov hnyav thiab tswj kev qab los noj mov, thiab txheeb xyuas nws cov txiaj ntsig kho mob.

——POMC cov ntaub ntawv ntsuas pom tias 80% (n=8/10) ntawm POMC cov neeg tsis rog rog ua tiav qhov hnyav poob ntawm> 10% (p< 0.0001)="" tsis="" pub="" dhau="" ib="" xyoos,="" thiab="" 50="" %="" ntawm="" cov="" neeg="" mob="" qhia="" txog="" lawv="" tus="" kheej="" kev="" tshaib="" nqhis="" kev="" txhim="" kho="" mus="" txog="" lossis="" ntau="" dua="" 25%="" (p="0.0004)," qhov="" hnyav="" tau="" txo="" los="" ntawm="" qhov="" nruab="" nrab="" ntawm="" 25.6%="" los="" ntawm="" lub="" hauv="" paus="">< 0.0001),="" qhov="" ntsuas="" tshaib="" plab="" tshaj="" plaws="" tau="" txo="" los="" ntawm="" qhov="" nruab="" nrab="" ntawm="" 27.1%="" los="" ntawm="" cov="" hauv="" paus="" (p="0.0005)," thiab="" qhov="" hnyav="" hnyav="" nruab="" nrab="" yog="" 31.2="" kg="" tom="" qab="" ib="" xyoos="" ntawm="" kev="" kho="" (70.5="">

——LEPR cov ntaub ntawv ntsuas pom tias 45.5% (n=5/11) ntawm LEPR cov neeg tsis muaj rog ua tiav qhov hnyav poob ntawm> 10% (p=0.0001) hauv ib xyoos, thiab 73% ntawm cov neeg mob nws tus kheej -cov ntaub ntawv txhim kho lawv cov qhab nia tshaib plab nce mus txog lossis ntau dua 25% (p< 0.0001),="" qhov="" hnyav="" tau="" txo="" los="" ntawm="" qhov="" nruab="" nrab="" ntawm="" 12.5%="" ​​los="" ntawm="" lub="" hauv="" paus="">< 0.0001),="" qhov="" ntsuas="" tshaib="" plab="" tshaj="" plaws="" tau="" txo="" los="" ntawm="" qhov="" nruab="" nrab="" ntawm="" 43.7%="" los="" ntawm="" cov="" hauv="" paus="">< 0.0001),="" thiab="" qhov="" hnyav="" nruab="" nrab="" poob="" 16.7="" kg="" (36.8)="" tom="" qab="" ib="" xyoos="" ntawm="" kev="" kho="">

Hauv ob txoj kev tshawb fawb no, cov neeg mob hnub nyoog 6-17 xyoo (n=14) muaj qhov txo qis hauv BMI ntawm lub hauv paus. Txij li cov neeg mob no tseem tsis tau ua tiav lawv txoj kev loj hlob, kev tsim nyog tsim nyog ntawm puberty thiab nce qhov siab tau pom nyob rau lub sijhawm kawm.

Ib qho ntxiv, ob qho kev tshawb fawb suav nrog 4-lub lim tiam cov placebo thim sij hawm ntxiv los qhia ntxiv txog cov txiaj ntsig ntawm kev kho setmelanotide. Hauv lub sijhawm no, cov neeg mob yuav luag hnyav tam sim ntawd, nce kev tshaib kev nqhis, thiab thim rov qab thawj 12 lub lis piam ntawm qhov hnyav thiab txo cov qhab nia tshaib plab. qhov sib ntawm.

Zoo ib yam nrog kev paub dhau los ntawm kev kho mob, setmelanotide tau ua zoo rau hauv ob qho kev sim. Cov xwm txheej tsis zoo (AEs) cuam tshuam nrog kev kho mob suav nrog qhov chaw txhaj tshuaj, xeev siab thiab ntuav, mob taub hau, thiab ua kom cov xim ntau ntxiv (tawv nqaij tsaus). Tsis tau muaj teeb meem plawv mob ntsig txog setmelanotide tau tshaj tawm.