Iovance Biotherapeutics 'yekutanga-ye-yayo-mhando immunotherapy yakabvumidzwa neFDA. Izvi zvinoreva kuti T-cell therapy, iyo yakashandura nzira iyo mamwe marudzi ekenza yeropa inorapwa, ikozvino inogona kushandiswa zvakananga pamamota akasimba.
Mushonga uyu ndeyekutanga yakasarudzika bundu-infiltrating lymphocyte (TIL) kurapwa kurova pamusika. Inonzi Amtagvi kana lifileucel. Iyo FDA yakamhanyisa maitiro ekubvumidza neChishanu kune vanhu vane melanoma yepamusoro avo vakatorapwa nePD-1 inhibitor kana BRAF inhibitor kana tumarara ine BRAF V600 gene.
Mutengo wemushonga wakakwira zvishoma pane mitengo yemazuva ano eCAR-T cell therapies, iyo kune vanhu vane gomarara reropa inoita $500,000 kana kuti isingasviki. Imhaka yekuti Iovance yaifunga kuti Amtagvi yaive yakakosha semushonga wekutanga wakatenderwa rudzi urwu rwe melanoma mushure mePD-1, uye vakatarisawo mamwe madhiragi akafanana, Vogt akadaro.
Kufanana nemamwe CAR-T masero ekurapa, Amtagvi inogadzirwa kubva kune immune masero akatorwa kubva kune chaivo varwere. TIL masero kubva mubundu rakabviswa remurwere anoshandiswa kugadzira chigadzirwa chekupedzisira. Masero aya anobva akura kunze kwemuviri obva aiswa jekiseni zvakare kumurwere.
Iwo immune system inogadzira masero eTIL ari ega, ayo anogona kuwana akasiyana mamaki pamusoro pemasero egomarara uye kurwisa iwo. Amtagvi inongopa muviri kuwanda kweaya maseru anorwisa gomarara nekuti masero emuviri ekudzivirira anorasikirwa nekushanda kwawo nekufamba kwenguva.
Pamberi peAmtagvi, Mishonga yeCAR-T inogona chete kurwisa mamwe marudzi egomarara reropa. Izvi zvinodaro nekuti mabundu akasimba haana chaiwo maseru-pamusoro biomarkers eCAR-T maseru ekunanga. Dambudziko iri rinogona kugadziriswa neTIL kurapwa, sezvo TIL masero akagadzikwa kuti awane biomarkers yegomarara.
Muchidzidzo cheruoko rumwe, Amtagvi panguva yazvino-inokurudzirwa dosi renji yakanyungudutsa mapundu mu31.5% yevarwere makumi manomwe nevatatu vanga vatorapwa neanti-PD-73 mushonga. 1% yeavo vakapindura vakanga vari mukuregererwa kwegore rinopfuura mushure memwedzi ye43.5 yekutevera.
Chiyero chekupindura chinangwa chaive chakafanana pa31.4% mukutsigira kwakabatanidzwa kudzidza kwakanaka kwakatarisa varwere ve153. Zvakare, 56.3% yevakapindura vachine mhinduro mushure megore. Chitsva chekuvandudza kuongororo yakasanganiswa yakaratidza kuti varwere vaigara avhareji yemwedzi ye13.9, uye inoda kusvika hafu yavo vachiri vapenyu mushure memakore mana. Ruzivo urwu haruna kuverengerwa mune yazvino label.
Kunyangwe Amtagvi iri nhanho hombe kumberi, haina kukwana.
Chekutanga, nekuti Amtagvi inogadzirwa kubva kumaseru eTIL kubva mubundu remurwere, hazvishande kune vanhu vasingakwanise kuvhiyiwa kana vasina bundu rakakwana rakabviswa.
Chechipiri, mushonga unouya nebhokisi yambiro pamusoro pekufa kwakabatana nekurapa, yakanyanya cytopenia inogara kwenguva yakareba, hutachiona hwakanyanya, uye kukuvara kwemoyo, mapapu, uye itsvo. Izvi zvinoreva kuti mushonga unogona kutengwa chete kune dzimwe nzvimbo dzekurapisa dziri mukati mezvipatara munogara vanhu. Chiratidzo chakatenderwa neFDA chemushonga uyu chinotiwo varwere vanofanirwa kutariswa mhedzisiro munzvimbo inochengeterwa varwere uye vawane ruzivo rwenyanzvi.
Vogt achiri kutaura kuti yambiro yebhokisi yeAmtagvi iri nani pane zviri kuitika neCAR-Ts yazvino. Semuenzaniso, Amtagvi haisi kudzorwa nechirongwa chekuchengetedza chinodiwa neFDA. Chirongwa ichi chinonzi ongororo yenjodzi uye nzira dzekudzikisa. Zvakare, mushonga hauna yambiro nezve cytokine release syndrome kana hemophagocytic lymphohistiocytosis, migumisiro miviri yeCAR-T cell treatments inogona kuva nengozi zvikuru uye kunyange kuuraya.
Vogt akataura kuti yambiro yebhokisi yaitarisirwa uye kuti vanachiremba vatoziva kuti mushonga wakaita sei.
Jim Ziegler, mukuru wekushambadzira weIovance, akataura parunhare kuti kambani iri munzira yekuve nenzvimbo dzinopfuura makumi mashanu mumazuva angangoita zana. Nzvimbo makumi matatu dzakatovakwa uye dzagadzirira kurapa varwere kana mushonga watanga kutengeswa.
Pakave nematambudziko ekuwanikwa nehuwandu hweCAR-T marapirwo, kunyanya panguva yekutanga chikamu. "Tine mukana wakakwana sezvo tiri kukwira masaiti aya nenzira yakadzora uye yakarongeka," Ziegler akadaro nezvekutanga kweAmtagvi. Nzvimbo yePhiladelphia iyo inoshanda nekambani uye mugadziri wekondirakiti ari padyo anogona kupedzisira ashandira "zviuru zvevarwere pagore," akadaro Vogt.
WuXi STA, chikamu cheWuXi AppTec, akataura mukutaura neChipiri kuti chirimwa chayo muPhiladelphia chakapihwa mvumo neFDA yekuyedza nekugadzira Amtagvi.
Maitiro ekugadzira amtagvi anogona kutora nguva yakareba. Parizvino, Iovance anofunga kuti avhareji yenguva inotora kugadzira chigadzirwa — kubva panosvika bundu kufekitari kusvika painobuda chigadzirwa — ichava mazuva makumi matatu nemana. Usakanganwa nguva inotora kutumira.
Vamwe vanhu vanogona kunge vaine dambudziko nekumirira kwenguva refu. Chidzidzo chekushanda kwemushonga chakabatanidzwa chakatanga chakatarisa varwere zana nemakumi masere nevapfumbamwe, asi makumi matatu nevatatu havana kuwana mushonga nekuda kwezvinhu zvakaita sevarwere vasere vasingawane chigadzirwa kana chirwere chavo chichiwedzera kana kufa.
Zvakare, varwere vanofanirwa kupfuura nekuwanda kwekurapa kwakaoma vasati vagamuchira Amtagvi. Izvi zvinoitirwa kuti muviri ugadzirire kubayiwa kana kuita kuti masero ave neutano hwakanaka kana kubata nemhedzisiro. Zvakare, varwere vanofanirwa kugara mukati memaawa maviri enzvimbo yekurapa kwe "mavhiki akati wandei" kuti vatarise mhedzisiro. Aya matanho anozodhura mari yakawanda uye kuita kuti zvinhu zviomere varwere.
Vanobhadhara vakati vanofarira kukosha kwekupihwa kweAmtagvi, kunyangwe ichidhura zvakanyanya, Ziegler akadaro. Kubva pane zvakataurwa naIovance kune vanobhadhara kusvika parizvino, kambani inofunga kuti ichawana kufukidzwa kwakafanana neazvino CAR-T marapirwo, paine kudiwa kwemvumo yekutanga, akadaro.
Iyo FDA yakabvumidza Amtagvi kuburikidza nekukurumidza ongororo maitiro. Iovance iri kuitawo chikamu chechitatu chidzidzo chine zita rekodhi TILVANCE-3 kuve nechokwadi chekuti mushonga unoshanda munyika chaiyo. Chidzidzo ichi chinofananidza Amtagvi neKeytruda, PD-301 inhibitor kubva kuMerck & Co., inopesana neKeytruda pachayo muvanhu vane melanoma vasati varapwa.
Yakanga iri nzira refu uye yakaoma yekuita kuti icon yeAmtagvi icheneswe. Iovance akange aronga kufaira muna 2020, asi aifanira kushandura hurongwa hwavo apo FDA yakasimudza kushushikana nezve bvunzo dzavakashandisa kuona kuti kurapa kwega kwega kwaive kwakadii. Nerubatsiro rwebvunzo, kambani yakakwanisa kuita kuti chikumbiro chayo chibvumirwe neFDA nekukurumidza muna Chivabvu 2023. Asi iyo FDA yakabva yatambanudza ongororo yayo nekuti iyo agency yakanga isina zviwanikwa zvakakwana.
Munguva yekunonoka, Vogt akambotora seMutungamiriri mukuru kubva kuna Maria Fardis, Ph.D., uyo akanga ambotungamirira. Kaputeni akatsiga haana kusarudzwa.
Iovance iri kushandawo pamushonga weTIL unonzi LN-145, uri kuedzwa muchikamu chechipiri chesero risiri diki. kenza yemapapu mushure mePD-1. Iovance akati gore rapfuura iyo yakakosha IOV-LUN-202 kuyedza inogona zvakare kukurumidzira maitiro ekubvisa.
Amtagvi inogadzirwa nekushandisa masero edziviriro kubva kumurwere wega wega, senge ikozvino CAR-T cell kurapwa. Chigadzirwa chekupedzisira chinogadzirwa nekukohwa TIL masero emurwere kubva pachikamu chebundu ravo rakabviswa akavhiyiwa, achiawedzera kunze, obva aaunza zvakare mumuviri wemurwere.
Iwo immune system inoburitsa TIL masero anogona kuona mamwe mamaki pamasero egomarara uye otanga mhinduro yekudzivirira. Amtagvi inozadza muviri nemasero ekudzivirira kenza sezvo maseru anogadzirwa achipera simba nezera.
Amtagvi isati yasvika, marapiro eCAR-T aingogumira pakugadzirisa mamwe magomarara eropa nekuda kwekushaikwa kwezviratidziro zvemasero-pameso mumamota akasimba kuti masero eCAR-T atarise. TIL kurapa inogadzirisa nyaya nekushandisa TIL masero akarongedzerwa kuti aone cancer biomarkers.
Amtagvi, inopihwa padanho rakatenderwa dosage muchidzidzo cheruoko rumwe, zvakakonzera kudzikiswa kwebundu mu31.5% yevarwere makumi manomwe nevatatu vaive vambosangana neanti-PD-73 kurapwa. Mushure memwedzi ye1, 18.6% yevatori vechikamu vakapindura kurapwa vakanga varamba vari mukuregererwa kwegore.
Ongororo yekuunganidza data kubva kuvarwere ve153 yakaratidza kuenzaniswa kwechinangwa chekupindura mwero we31.4%. Pamusoro pezvo, 56.3% yevatori vechikamu vakachengeta mhedzisiro yenguva refu mushure megore rimwe. Kuvandudzwa kwechangobva kuitika kwedata rakabatanidzwa kwakaratidza kuti varwere vaive nepakati pekupona kwemwedzi 13.9, paine inenge hafu yevarwere vachiri kurarama mushure memakore mana, kunyangwe zvisina kutaurwa pane yazvino label.
Amtagvi, kunyangwe yakagadziridza, haina kukanganisa.
Nekuda kwekushandiswa kwemaseru eTIL kubva mubundu remurwere, vanhu vasingakwanise kuvhiyiwa kana vasina akakwana akabviswa bundu tishu havakodzere kurapwa kweAmtagvi.
Mushonga une yambiro yebhokisi yekufa kwakabatana nekurapa, yakaramba yakasimba cytopenia, hutachiona hwakanyanya, uye kukuvara kwemoyo neitsvo. Mushonga uyu unowanikwa chete kunzvimbo dzekurapisa mukati mechipatara chevarwere. Mushonga weFDA-wakatenderwa label inoraira varwere kuti vatariswe mhedzisiro munzvimbo inochengeterwa varwere zvakanyanya uye inoda kuti nyanzvi dzivepo.
Vogt akapokana kuti yambiro yebhokisi yeAmtagvi ndeyekuvandudza kana ichienzaniswa nemamiriro ezvinhu aripo neCAR-Ts iripo. Amtagvi haina kudzorwa pasi peiyo FDA-yakatenderwa kuchengetedza chirongwa chinodaidzwa kuti njodzi yekuongorora uye yekuderedza matanho. Mushonga hauna yambiro cytokine release syndrome kana kuti hemophagocytic lymphohistiocytosis, zvinova zvakakomba zvinokonzerwa neCAR-T cell therapy.
Vogt akataura kuti yambiro yebhokisi yaitarisirwa uye kuti varapi vatoziva nezvemishonga yemushonga.
Iovance yakanyora nzvimbo makumi matatu dzakatarwa dzakagadzirirwa kurapa varwere pakuburitswa kwemushonga, nehurongwa hwekuwedzera nzvimbo dzinopfuura makumi mashanu mukati memazuva angangoita zana, sezvakataurwa nemukuru wezvekutengesa weIovance, Jim Ziegler.
Multiple CAR-T marapirwo akatarisana nekushomeka kwekushandisa, kunyanya panguva yekutanga kuburitswa. Ziegler akataura kuti kune mukana wakakwana wekuvhurwa kweAmtagvi sezvo vari kuwedzera zvishoma nezvishoma aya masayiti nenzira yakarongeka uye nenzira. Vogt akataura kuti nzvimbo yekambani muPhiladelphia uye mugadziri wekondirakiti yakavakidzana aikwanisa kurapa zviuru zvevarwere pagore.
NeChipiri, WuXi STA, mubatsiri weWuXi AppTec, yakazivisa kuti nzvimbo yayo yePhiladelphia yakabvumidzwa neFDA kuti iite ongororo yekuongorora uye kugadzirwa kweAmtagvi.
Amtagvi inogona kunge iine maitiro akareba ekugadzira. Iovance inofungidzira kuti avhareji yekugadzira maitiro, kubva pakusvika bundu panzvimbo yekugadzira kusvika kune yekupedzisira kuburitswa kwechigadzirwa, ichave mazuva makumi matatu nemana. Kusasanganisa nguva yekutumira.
Kumira kwenguva refu kunogona kuunza dambudziko kune vamwe varwere. Mushonga uyu wakasanganiswa kushanda kwekuongorora kwakatanga kuve nevarwere zana nemakumi masere nevapfumbamwe, asi makumi matatu nevatatu havana kuwana mushonga nekuda kwezvikonzero zvakaita sekutadza kugadzira chigadzirwa kuvarwere vasere uye kufambira mberi kwechirwere kana kufa kwevarwere gumi nemumwe.
Varwere vanogashira marapirwo akaomarara pamberi uye mushure mekutonga kweAmtagvi kuti ive yekutanga muviri kuti infusion, kusimudzira kushanda kwesero, kana kugadzirisa mhedzisiro. Varwere vanofanirwa kugara mukati memaawa maviri enzvimbo yekurapa kwe "mavhiki akati wandei" kutarisa mhedzisiro. Aya maitiro anozokonzera kuwedzera mari uye kuomerwa kwemuviri kuvarwere.
Ziegler akataura kuti vanobhadhara vabvuma kukosha kweAmtagvi kunyangwe mutengo wayo wakakwira. Iovance inotarisira kuchengetedza kuvharika kunofananidzwa nearipo eCAR-T marapirwo, aine mvumo yekutanga, zvichibva pahurukuro dzayo nevabhadhara.
Amtagvi yakabvumidzwa neFDA ichishandisa nzira yekukurumidza yekubvumidza. Iovance yave kupedzisa kuyedza kwechikamu chechitatu chinonzi TILVANCE-3 kuratidza kushanda kwemushonga. Muedzo uyu uri kuenzanisa musanganiswa weAmtagvi neMerck & Co.'s PD-301 inhibitor Keytruda nekushandisa Keytruda chete muvarwere vemelanoma vasina kurapwa.
Maitiro ekubvumidza kwaAmtagvi aive akaoma uye akaoma. Iovance akange aronga kuendesa faira muna 2020 asi akarimisa nekuda kwekubvunza kweFDA pamusoro pemayedzo anoshandiswa kuyera simba remushonga wega wega wekurapa. Muna Chivabvu 2023, kambani yakabudirira kukunda chipingamupinyi uye yakaita kuti chikumbiro chayo chigamuchirwe neFDA kuti chiongororwe. Iyo FDA yakawedzera ongororo yayo nekuda kwekuomerwa nezviwanikwa mubazi.
Vogt akatora chinzvimbo cheMutungamiriri wenguva pfupi muna 2021, achitsiva CEO Maria Fardis, Ph.D., panguva yekunonoka. Hapana mubatsiri wechigarire akagadzwa.
Iovance iri kugadzira chirongwa cheTIL chinonzi LN-145, chiri kuita chikamu chechipiri kliniki miedzo ye-post-PD-1 isiri-diki yekenza yemapapu, kuwedzera kune Amtagvi. Gore rapfuura, Iovance akataura kuti kutongwa kwakakosha kweIOV-LUN-202 kunogona kutungamira kubvumidzwa nekukurumidza.
