Idatha yeSigaba III ngomuthi omusha waseShayina womqhele womlomo ku-NEJM ikhombisa ukusebenza kahle okungaphansi kwePaxlovid

Emahoreni okuqala ka-29 Disemba, i-NEJM yashicilela ku-inthanethi ucwaningo olusha lwesigaba sesi-3 lwe-coronavirus entsha yaseShayina i-VV116. Imiphumela ibonise ukuthi i-VV116 yayingeyimbi kakhulu kune-Paxlovid (nematovir/ritonavir) ngokwesikhathi sokululama emtholampilo futhi yayinezigameko ezimbalwa ezimbi.

Umthombo wesithombe: NEJM

Isikhathi esimaphakathi sokululama yizinsuku ezi-4, izinga lezehlakalo ezimbi lingu-67.4%

I-VV116 umuthi womlomo we-nucleoside olwa ne-coronavirus entsha (SARS-CoV-2) owenziwe ngokubambisana ne-Junsit kanye ne-Wang Shan Wang Shui, futhi ungumvimbeli we-RdRp kanye ne-remdesivir yase-Gilead, i-Merck Sharp & Dohme's molnupiravir kanye ne-azelvudine ye-Real Biologics.

Ngo-2021, kwaqedwa isivivinyo sezokwelapha sesigaba sesi-2 se-VV116 e-Uzbekistan. Imiphumela yocwaningo ibonise ukuthi iqembu le-VV116 lingathuthukisa kangcono izimpawu zomtholampilo futhi linciphise kakhulu ingozi yokuqhubekela phambili esimweni esibucayi nokufa uma kuqhathaniswa neqembu lokulawula. Ngokusekelwe emiphumeleni emihle yalolu cwaningo, i-VV116 ivunyelwe e-Uzbekistan ekwelapheni iziguli ezine-COVID-19 ephakathi nendawo kuya kwenzima, futhi isibe umuthi wokuqala omusha we-coronary ophuzwayo ovunyelwe ukumaketha kwamanye amazwe eShayina [1].

Lolu vivinyo lwezokwelapha lwesigaba sesi-3 [2] (NCT05341609), oluholwa nguSolwazi Zhao Ren waseShanghai Ruijin Hospital, uSolwazi Gaoyuan waseShanghai Renji Hospital kanye noSolwazi uNing Guang waseShanghai Ruijin Hospital, luqediwe ngesikhathi sokuqubuka kwesifo okubangelwe yi-Omicron variant (B.1.1.529) kusukela ngoMashi kuya kuMeyi eShanghai, ngenhloso yokuhlola ukusebenza kahle nokuphepha kwe-VV116 vs Paxlovid ekwelashweni kwasekuqaleni kweziguli ezine-COVID-19 emnene kuya kwephakathi. Inhloso kwakuwukuhlola ukusebenza kahle nokuphepha kwe-VV116 vs Paxlovid ekwelashweni kwasekuqaleni kweziguli ezine-COVID-19 emnene kuya kwephakathi.

Umthombo wesithombe: Ireferensi 2

Ukuhlolwa kweziguli ezingama-822 zabantu abadala be-Covid-19 ezisengozini enkulu yokuqhubeka nesifo futhi ezinezimpawu ezincane kuya kweziphakathi kwenziwa phakathi kuka-4 Ephreli no-2 Meyi 2022 ukuze kuhlolwe ukufaneleka kwabahlanganyeli abavela ezibhedlela eziyisikhombisa eShanghai, eShayina. Ekugcineni, ababambiqhaza abangu-771 bathole i-VV116 (384, 600 mg njalo emahoreni ayi-12 ngosuku loku-1 kanye no-300 mg njalo emahoreni ayi-12 ngosuku lwesibili kuya kolwesihlanu) noma i-Paxovid (387, 300 mg nimatuvir + 100 mg ritonavir njalo emahoreni ayi-12 izinsuku ezi-5) njengomuthi womlomo.

Imiphumela yalolu cwaningo lwezokwelapha ikhombisile ukuthi ukwelashwa kwasekuqaleni nge-VV116 ye-COVID-19 emnene kuya kwephakathi kwahlangabezana nephuzu eliyinhloko (isikhathi sokululama okuqhubekayo kwezokwelapha) okwabikezelwa yiphrothokholi yezokwelapha: isikhathi esimaphakathi sokululama kwezokwelapha kwakuyizinsuku ezi-4 eqenjini le-VV116 kanye nezinsuku ezi-5 eqenjini le-Paxlovid (isilinganiso sezingozi, 1.17; 95% CI, 1.02 kuya ku-1.36; umkhawulo ophansi. >0.8).

Ukugcina isikhathi sokululama emtholampilo

Iziphetho zokusebenza kahle okuyinhloko nokwesibili (ukuhlaziywa okuphelele kwabantu)

Umthombo wesithombe: Ireferensi 2

Ngokuphepha, ababambiqhaza abathola i-VV116 babike izehlakalo ezimbi ezimbalwa (67.4%) kunalabo abathola i-Paxlovid (77.3%) ekulandeleni kwezinsuku ezingama-28, futhi izehlakalo zezehlakalo ezimbi zeBanga lesi-3/4 zaziphansi ku-VV116 (2.6%) kunaku-Paxlovid (5.7%).

Izehlakalo ezimbi (abantu abaphephile)

Umthombo wesithombe: Ireferensi 2

Izimpikiswano nemibuzo

Ngomhlaka-23 Meyi 2022, uJuniper wembula ukuthi ucwaningo lwezokwelapha lokubhaliswa kweSigaba III lwe-VV116 uma kuqhathaniswa ne-PAXLOVID lokwelashwa kwasekuqaleni kwe-COVID-19 emnene kuya kwephakathi (NCT05341609) lufinyelele esiphethweni salo esiyinhloko socwaningo.

Umthombo wesithombe: Ireferensi 1

Ngesikhathi lapho imininingwane yocwaningo yayingekho, impikiswano ezungeze ucwaningo lweSigaba III yayikabili: okokuqala, kwakuyisifundo esingaboni muntu futhi, uma kungekho kulawulwa kwe-placebo, kwakwesatshwa ukuthi kuzoba nzima ukwahlulela umuthi ngobuqotho ngokuphelele; okwesibili, kwakunemibuzo mayelana neziphetho zezokwelapha.

Izindlela zokufaka emtholampilo zeJuniper (i) imiphumela emihle yokuhlolwa okusha komqhele, (ii) uphawu olulodwa noma ngaphezulu lwe-COVID-19 oluthambile noma oluphakathi, kanye (iii) neziguli ezisengozini enkulu ye-COVID-19 embi kakhulu, okuhlanganisa nokufa. Kodwa-ke, ukuphela kokuphela kwesifo esiyinhloko 'isikhathi sokululama okuqhubekayo kwezokwelapha'.

Ngaphambi nje kwesimemezelo, ngoMeyi 14, uJuniper wayebuyekeze iziphetho zezokwelapha ngokususa enye yeziphetho zezokwelapha eziyinhloko, "isilinganiso sokuguqulwa kube ukugula okukhulu noma ukufa" [3].

Umthombo wesithombe: Ireferensi 1

La maphuzu amabili ayinhloko okuphikiswana ngawo nawo akhulunywe ngawo ngqo ocwaningweni olushicilelwe.

Ngenxa yokuqubuka okungazelelwe kwe-Omicron, ukukhiqizwa kwamaphilisi e-placebo e-Paxlovid kwakungakaqedwa ngaphambi kokuqala kwesilingo ngakho-ke abaphenyi babengenakukwazi ukuqhuba lolu vivinyo besebenzisa umklamo ongaboni kabili, ongabonakali kabili. Ngokuphathelene nesici esingaboni esisodwa sesilingo somtholampilo, uJuniper uthe le nqubo yenziwa ngemuva kokuxhumana neziphathimandla ezilawulayo nokuthi umklamo ongaboni oyedwa usho ukuthi umphenyi (kufaka phakathi umhloli we-endpoint yesifundo) noma umxhasi ngeke azi ukwabiwa kwemithi ethile yokwelapha kuze kube yilapho i-database yokugcina ivaliwe ekupheleni kwesifundo.

Kuze kube yisikhathi sokuhlaziywa kokugcina, akekho kwabahlanganyeli esivivinyweni owayeke wafa noma waqhubekela phambili emcimbini onzima we-Covid-19, ngakho-ke akukho ziphetho ezingathathwa mayelana nokusebenza kahle kwe-VV116 ekuvimbeleni ukuqhubekela phambili e-Covid-19 noma ukufa okubi kakhulu noma okubi kakhulu. Idatha ibonise ukuthi isikhathi esimaphakathi esilinganisiwe kusukela ekungahleliwe kuya ekubuyeleni okuqhubekayo kwezimpawu ezihlosiwe ezihlobene ne-Covid-19 kwakuyizinsuku eziyi-7 (95% CI, 7 kuya ku-8) kuwo womabili amaqembu (isilinganiso sengozi, 1.06; 95% CI, 0.91 kuya ku-1.22) [2]. Akunzima ukuchaza ukuthi kungani isiphetho esiyinhloko 'sezinga lokuguqulwa liye ekuguleni okubi noma ekufeni', esasibekwe ekuqaleni ngaphambi kokuphela kwesivivinyo, sasuswa.

Ngomhlaka-18 Meyi 2022, iphephandaba i-Emerging Microbes & Infections lashicilela imiphumela yesivivinyo sokuqala sezokwelapha se-VV116 ezigulini ezinegciwane le-Omicron [4], ucwaningo oluvulekile nolulindelekile lweqembu labantu abangu-136 abaqinisekisiwe ukuthi bangeniswe esibhedlela.

Idatha evela ocwaningweni ibonise ukuthi iziguli ezinegciwane le-Omicron ezisebenzise i-VV116 zingakapheli izinsuku ezi-5 zokuhlolwa kwazo kokuqala kwe-nucleic acid zazinesikhathi sokubuyela emuva kwe-nucleic acid ezinsukwini ezingu-8.56, ngaphansi kwezinsuku ezingu-11.13 eqenjini lokulawula. Ukunikezwa kwe-VV116 ezigulini ezinezimpawu phakathi nesikhathi salolu cwaningo (izinsuku ezingu-2-10 zokuhlolwa kokuqala kwe-nucleic acid) kunciphisa isikhathi sokubuyela emuva kwe-nucleic acid kuzo zonke iziguli. Ngokuphathelene nokuphepha kwemithi, akukho miphumela emibi emibi ebonwe eqenjini lokwelashwa le-VV116.

Umthombo wesithombe: Ireferensi 4

Kunezivivinyo ezintathu zemitholampilo eziqhubekayo ku-VV116, ezimbili zazo ziyizifundo zesigaba III ku-COVID-19 emnene kuya kwephakathi (NCT05242042, NCT05582629). Esinye isivivinyo se-COVID-19 esimaphakathi kuya kwesikhulu yisifundo semitholampilo sesigaba III esihlanganisa izikhungo eziningi zomhlaba wonke, esingahleliwe, esingaboni kabili (NCT05279235) sokuhlola ukusebenza kahle nokuphepha kwe-VV116 uma kuqhathaniswa nokwelashwa okujwayelekile. Ngokusho kwesimemezelo sikaJuniper, isiguli sokuqala sabhaliswa futhi sanikezwa umuthi ngoMashi 2022.

Umthombo wesithombe: clinicaltrials.gov

Izinkomba：

[1]I-Junshi Biotech: Isimemezelo ngephuzu eliyinhloko lesifundo somtholampilo esibhalisiwe seSigaba III se-VV116 ngokumelene ne-PAXLOVID sokwelashwa kwasekuqaleni kwe-COVID-19 emnene kuya kwephakathi.

[2]https://www.nejm.org/doi/full/10.1056/NEJMoa2208822?query=featured_home[3]https://clinicaltrials.gov/ct2/show/record/NCT05341609[4] Ensi Ma, Jingwen Aiming Gau Zheng, Juming Xiao Zhang Yin, Zhiren Fu, Hao Xing, Li Li, Liying Sun, Heyu Huang, Quanbao Zhang, Linlin Xu, Yanting Jin, Rui Chen, Guoyue Lv, Zhijun Zhu, Wenhong Zhang, Zhengxin Wang. (2022) Iphrofayili yokutheleleka kwe-Omicron kanye nesimo sokugoma phakathi kwabamukeli bokufakelwa kwesibindi abangu-1881: iqoqo le-multi-centre retrospective. I-Emerging Microbes & Infections 11:1, amakhasi 2636-2644.