{"id":4111,"date":"2025-07-16T17:52:36","date_gmt":"2025-07-16T14:52:36","guid":{"rendered":"https:\/\/dmdwarrior.com\/?p=4111"},"modified":"2025-07-16T18:11:10","modified_gmt":"2025-07-16T15:11:10","slug":"fda-rejection-letter-vyondys-53-golodirsen","status":"publish","type":"post","link":"https:\/\/dmdwarrior.com\/tr\/fda-rejection-letter-vyondys-53-golodirsen\/","title":{"rendered":"Vyondys 53: FDA Red Mektubu Ne Anlama Geliyor?"},"content":{"rendered":"<p class=\"wp-block-paragraph\">G\u0131da ve \u0130la\u00e7 Dairesi (FDA), per\u015fembe g\u00fcn\u00fc ila\u00e7lar\u0131 reddedilen \u015firketlere g\u00f6nderdi\u011fi 200&#039;den fazla mektubu yay\u0131mlayarak, ila\u00e7 inceleme s\u00fcrecinin bazen g\u00f6zden ka\u00e7an bir k\u0131sm\u0131na dikkat \u00e7ekti. <strong>Bu ret mektuplar\u0131ndan biri, Sarepta Therapeutics taraf\u0131ndan \u00fcretilen ve ekzon 53 atlama tedavisi i\u00e7in geli\u015ftirilen Vyondys 53 (golodirsen) adl\u0131 ila\u00e7 i\u00e7in g\u00f6nderilmi\u015fti.<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Kurum, yaln\u0131zca \u00fcr\u00fcnleri nihayetinde onaylanan ve \u00e7o\u011fu y\u0131llar i\u00e7inde piyasaya s\u00fcr\u00fclen \u00fcreticilere g\u00f6nderilen mektuplara odakland\u0131. T\u00fcm mektuplar\u0131 tek bir yerde toplayan kurum, bu faaliyetin \u015feffafl\u0131\u011f\u0131 te\u015fvik etmeye y\u00f6nelik daha geni\u015f kapsaml\u0131 bir \u00e7aban\u0131n par\u00e7as\u0131 oldu\u011funu iddia etti.<\/p>\n\n\n\n<div class=\"wp-block-rank-math-toc-block\" id=\"rank-math-toc\"><h2>\u0130\u00e7indekiler<\/h2><nav><ul><li><a href=\"#details-of-fda-rejection-letter-about-vyondys-53\">Vyondys 53 Hakk\u0131nda FDA Red Mektubunun Ayr\u0131nt\u0131lar\u0131<\/a><\/li><li><a href=\"#dystrophin-level-increased-9-parts-in-a-thousand\">Distrofin seviyesi binde 9 oran\u0131nda artt\u0131<\/a><\/li><li><a href=\"#clinical-effect-of-vyondys-53\">Vyondys 53&#039;\u00fcn Klinik Etkisi<\/a><\/li><li><a href=\"#serious-side-effects-of-vyondys-53-according-to-the-fda\">FDA&#039;ye G\u00f6re Vyondys 53&#039;\u00fcn Ciddi Yan Etkileri<\/a><\/li><li><a href=\"#how-was-vyondys-53-approved\">Vyondys 53 Nas\u0131l Onayland\u0131?<\/a><\/li><li><a href=\"#pharmaceutical-companies-dont-publish-all-information\">\u0130la\u00e7 \u015eirketleri T\u00fcm Bilgileri Yay\u0131nlam\u0131yor<\/a><\/li><\/ul><\/nav><\/div>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"details-of-fda-rejection-letter-about-vyondys-53\">Vyondys 53 Hakk\u0131nda FDA Red Mektubunun Ayr\u0131nt\u0131lar\u0131<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">FDA, Duchenne kas distrofisi i\u00e7in ekzon 53 atlama tedavisi olan Vyondys 53 (golodirsen) i\u00e7in 2019 tarihli ret mektubunu yay\u0131nlad\u0131. <strong>FDA, tedaviyle sa\u011flanan \u201ck\u0131salt\u0131lm\u0131\u015f distrofin d\u00fczeylerindeki k\u00fc\u00e7\u00fck art\u0131\u015f\u201d g\u00f6z \u00f6n\u00fcne al\u0131nd\u0131\u011f\u0131nda, Vyondys 53&#039;\u00fcn klinik faydas\u0131n\u0131n muhtemelen \u201corant\u0131l\u0131 olarak k\u00fc\u00e7\u00fck\u201d olaca\u011f\u0131n\u0131 belirtmi\u015ftir.<\/strong><\/p>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"dystrophin-level-increased-9-parts-in-a-thousand\">Distrofin seviyesi binde 9 oran\u0131nda artt\u0131<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>FDA'n\u0131n Vyondys 53 (golodirsen) i\u00e7in yazd\u0131\u011f\u0131 ret mektubunda, ilac\u0131n kullan\u0131m\u0131ndan sonra distrofin seviyelerinde \u00e7ok k\u00fc\u00e7\u00fck bir art\u0131\u015f oldu\u011fu belirtildi<\/strong>:<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u00c7al\u0131\u015fmada de\u011ferlendirilebilen 25 hasta i\u00e7in, Western blot ile de\u011ferlendirilen ba\u015flang\u0131\u00e7 ortalama distrofin seviyesi 0,10 \u00b1 0,07 (normalin y\u00fczdesi; ortalama \u00b1 SD) idi. 48. haftada, ortalama distrofin seviyesi 1,02 \u00b1 1,03 (normalin y\u00fczdesi; ortalama \u00b1 SD) idi ve bu, normalin ortalama %0,92 \u00b1 1,01&#039;lik bir art\u0131\u015f\u0131na kar\u015f\u0131l\u0131k geliyordu.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Distrofindeki bireysel de\u011fi\u015fiklikler, verileri do\u011fru bir perspektife oturtmak ve etki b\u00fcy\u00fckl\u00fc\u011f\u00fcn\u00fcn abart\u0131lmas\u0131n\u0131 \u00f6nlemek i\u00e7in a\u015fa\u011f\u0131daki \u015eekil 1'de normal (100%) bir \u00f6l\u00e7ek kullan\u0131larak g\u00f6sterilmi\u015ftir. Kesik distrofindeki ortalama art\u0131\u015flar\u0131n, s\u0131ras\u0131yla ekson 53 ve ekson 51 atlamas\u0131na yatk\u0131n mutasyonlar\u0131 olan hastalarda golodirsen ve eteplirsen'e yan\u0131t olarak benzer oldu\u011funu fark ettiniz - mutlak ortalama art\u0131\u015flar 0,9%, yani binde 9. Biz de kat\u0131l\u0131yoruz.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Kesik distrofin d\u00fczeyinde binde 9 oran\u0131nda k\u00fc\u00e7\u00fck bir art\u0131\u015f\u0131n klinik fayday\u0131 tahmin etme olas\u0131l\u0131\u011f\u0131n\u0131n makul oldu\u011fu kabul edilirse, klinik faydan\u0131n da buna orant\u0131l\u0131 olarak k\u00fc\u00e7\u00fck olaca\u011f\u0131n\u0131 varsaymak makul g\u00f6r\u00fcnmektedir.<\/strong><\/p>\n\n\n\n<div><a href=\"https:\/\/dmdwarrior.com\/wp-content\/uploads\/2025\/07\/Vyondys-53-Study-4053-101.png\" class=\"td-modal-image\"><figure class=\"wp-block-image size-full\"><img loading=\"lazy\" decoding=\"async\" width=\"975\" height=\"884\" src=\"https:\/\/dmdwarrior.com\/wp-content\/uploads\/2025\/07\/Vyondys-53-Study-4053-101.png\" alt=\"Vyondys 53 (golodirsen) distrofin d\u00fczeyi\" class=\"wp-image-4115\" title=\"\" srcset=\"https:\/\/dmdwarrior.com\/wp-content\/uploads\/2025\/07\/Vyondys-53-Study-4053-101.png 975w, https:\/\/dmdwarrior.com\/wp-content\/uploads\/2025\/07\/Vyondys-53-Study-4053-101-300x272.png 300w, https:\/\/dmdwarrior.com\/wp-content\/uploads\/2025\/07\/Vyondys-53-Study-4053-101-768x696.png 768w, https:\/\/dmdwarrior.com\/wp-content\/uploads\/2025\/07\/Vyondys-53-Study-4053-101-13x12.png 13w, https:\/\/dmdwarrior.com\/wp-content\/uploads\/2025\/07\/Vyondys-53-Study-4053-101-463x420.png 463w, https:\/\/dmdwarrior.com\/wp-content\/uploads\/2025\/07\/Vyondys-53-Study-4053-101-150x136.png 150w, https:\/\/dmdwarrior.com\/wp-content\/uploads\/2025\/07\/Vyondys-53-Study-4053-101-696x631.png 696w\" sizes=\"auto, (max-width: 975px) 100vw, 975px\" \/><figcaption class=\"wp-element-caption\">Kaynak: FDA 211970Orig1s000<\/figcaption><\/figure><\/a><\/div>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"clinical-effect-of-vyondys-53\">Vyondys 53&#039;\u00fcn Klinik Etkisi<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">\u00c7al\u0131\u015fma 4053-101&#039;deki 6 dakikal\u0131k y\u00fcr\u00fcme verileri burada tart\u0131\u015f\u0131lmamakla birlikte, esasen t\u00fcm erkek \u00e7ocuklarda ilerleyici fiziksel i\u015flev kayb\u0131 g\u00f6stermektedir. Dahas\u0131, fiziksel performans\u0131n s\u00fcrd\u00fcr\u00fclmesi ile kesilmi\u015f distrofin \u00fcretiminin b\u00fcy\u00fckl\u00fc\u011f\u00fc aras\u0131nda bir korelasyon yoktur; bu da golodirsen&#039;in ger\u00e7ekten klinik bir etkisi varsa, etki boyutunun k\u00fc\u00e7\u00fck oldu\u011funu g\u00f6stermektedir.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"serious-side-effects-of-vyondys-53-according-to-the-fda\">FDA&#039;ye G\u00f6re Vyondys 53&#039;\u00fcn Ciddi Yan Etkileri<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">Aral\u0131k 2019&#039;da FDA, Sarepta&#039;n\u0131n Vyondys 53&#039;\u00fcn\u00fc, ekzon 53 atlamas\u0131na yatk\u0131n DMD hastalar\u0131 i\u00e7in ilk hedefli tedavi se\u00e7ene\u011fi olarak onaylad\u0131. Ancak ila\u00e7, d\u00f6rt ay \u00f6nce, o d\u00f6nemde \u0130la\u00e7 De\u011ferlendirme ve Ara\u015ft\u0131rma Merkezi&#039;nin \u0130la\u00e7 De\u011ferlendirme Ofisi ba\u015fkan\u0131 olan Ellis Unger taraf\u0131ndan imzalanan bir CRL&#039;de FDA taraf\u0131ndan reddedilmi\u015fti.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">FDA, reddin gerek\u00e7esinde, tedavinin uyand\u0131rd\u0131\u011f\u0131 &quot;kesik distrofin d\u00fczeyindeki k\u00fc\u00e7\u00fck art\u0131\u015f&quot; g\u00f6z \u00f6n\u00fcne al\u0131nd\u0131\u011f\u0131nda, Vyondys 53&#039;\u00fcn terap\u00f6tik etkisinin muhtemelen &quot;orant\u0131l\u0131 olarak k\u00fc\u00e7\u00fck&quot; olaca\u011f\u0131n\u0131 belirtti. Unger, Vyondys 53&#039;\u00fcn \u00e7ocuklarda \u00fcretti\u011fi distrofin miktar\u0131 ile fiziksel performanslar\u0131 aras\u0131nda &quot;bir ili\u015fki&quot; olmad\u0131\u011f\u0131n\u0131 ve ilac\u0131 ald\u0131ktan sonra muayene edilen \u00e7ocuklar\u0131n &quot;esas itibar\u0131yla tamam\u0131nda&quot; artan fiziksel i\u015flev kayb\u0131 g\u00f6r\u00fcld\u00fc\u011f\u00fcn\u00fc a\u00e7\u0131klayarak devam etti.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Sanki \u00e7\u00fcr\u00fckler yetmezmi\u015f gibi, Unger, Vyondys 53 kullan\u0131c\u0131lar\u0131n\u0131n u\u011fra\u015fmak zorunda kald\u0131\u011f\u0131 uzun bir g\u00fcvenlik endi\u015feleri listesi s\u0131ralad\u0131. Bunlar aras\u0131nda &quot;b\u00f6brek toksisitesi&quot; ve &quot;ila\u00e7 kullan\u0131m\u0131na ba\u011fl\u0131 ciddi enfeksiyonlar&quot; da vard\u0131. Her ikisinin de &quot;\u00f6l\u00fcmc\u00fcl olma potansiyeline sahip&quot; oldu\u011funu, ikincisinin ise &quot;izlenmesinin zor veya imkans\u0131z&quot; oldu\u011funu iddia ediyor.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Sarepta&#039;n\u0131n Elevidys gen terapisiyle ba\u011flant\u0131l\u0131 ciddi karaci\u011fer yetmezli\u011finden kaynaklanan iki \u00f6l\u00fcm g\u00f6z \u00f6n\u00fcne al\u0131nd\u0131\u011f\u0131nda, bu ikinci uyar\u0131 \u00f6zellikle endi\u015fe verici. Unger&#039;in mektupta belirtti\u011fi gibi, Vyondys 53, Elevidys gibi adeno-ili\u015fkili vir\u00fcs (AAV) tabanl\u0131 bir gen terapisinin aksine, bir antisens oligon\u00fckleotid (ASO) olmas\u0131na ra\u011fmen, her iki tedavi y\u00f6ntemi de karaci\u011fer hasar\u0131yla ili\u015fkilendirilmi\u015ftir.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Devam\u0131n\u0131 oku<\/strong>: <a href=\"https:\/\/dmdwarrior.com\/wp-content\/uploads\/2025\/07\/Vyondys-53-FDA-Rejection-Letter.pdf\">Vyondys 53 FDA Reddetme Mektubu<\/a><\/p>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"how-was-vyondys-53-approved\">Vyondys 53 Nas\u0131l Onayland\u0131?<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">D\u00fczenleyici kurumun CRL&#039;de dile getirdi\u011fi endi\u015feleri gidermek i\u00e7in Sarepta daha sonra itirazda bulundu ve FDA ile g\u00f6r\u00fc\u015ft\u00fc. Bu g\u00f6r\u00fc\u015fme, o d\u00f6nemde FDA&#039;nin Yeni \u0130la\u00e7lar Ofisi ba\u015fkan\u0131 olan Peter Stein&#039;\u0131n Nisan ay\u0131nda kurumdan ayr\u0131lmas\u0131yla sonu\u00e7land\u0131 ve Vyondys 53 onayland\u0131.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"pharmaceutical-companies-dont-publish-all-information\">\u0130la\u00e7 \u015eirketleri T\u00fcm Bilgileri Yay\u0131nlam\u0131yor<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">&quot;\u0130la\u00e7 geli\u015ftiricileri, FDA&#039;de gezinirken \u00e7ok uzun zamand\u0131r tahmin oyunu oynuyorlar,&quot; dedi FDA Komiseri Dr. Marty Makary, MPH. &quot;Hem ila\u00e7 geli\u015ftiricileri hem de sermaye piyasalar\u0131 \u00f6ng\u00f6r\u00fclebilirlik istiyor. Bu y\u00fczden bug\u00fcn, hastalara daha h\u0131zl\u0131 tedavi ve anlaml\u0131 tedaviler sunma nihai hedefimizle, bunu onlara sunmaya bir ad\u0131m daha yakla\u015ft\u0131k.&quot;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">FDA, bekleyen ba\u015fvurular i\u00e7in CRL yay\u0131nlamaktan tarihsel olarak ka\u00e7\u0131nd\u0131\u011f\u0131 i\u00e7in, sponsorlar genellikle FDA&#039;nin karar\u0131n\u0131n gerek\u00e7esini payda\u015flar\u0131na ve kamuoyuna yanl\u0131\u015f aktarmaktad\u0131r. FDA ara\u015ft\u0131rmac\u0131lar\u0131 taraf\u0131ndan 2015 y\u0131l\u0131nda yap\u0131lan bir analize g\u00f6re, sponsorlar ba\u015fvurular\u0131n\u0131n onaylanmad\u0131\u011f\u0131n\u0131 kamuoyuna duyururken FDA&#039;nin g\u00fcvenlik ve etkililik konusundaki endi\u015felerinden 85%&#039;ye de\u011finmekten ka\u00e7\u0131nm\u0131\u015ft\u0131r. Dahas\u0131, FDA g\u00fcvenlik veya etkililik i\u00e7in yeni bir klinik \u00e7al\u0131\u015fma talep etti\u011finde, bu kritik bilgi yakla\u015f\u0131k 40% zaman\u0131nda a\u00e7\u0131klanmamaktad\u0131r. Onaylanmayan ba\u015fvurulardan al\u0131nan dersler de sekt\u00f6rle payla\u015f\u0131lmamakta ve bu da \u015firketlerin benzer hatalar\u0131 tekrar tekrar yapmas\u0131na yol a\u00e7maktad\u0131r. \u2013 Devam\u0131n\u0131 Oku: <a href=\"https:\/\/www.fda.gov\/news-events\/press-announcements\/fda-embraces-radical-transparency-publishing-complete-response-letters\" target=\"_blank\" rel=\"noreferrer noopener\">FDA, Eksiksiz Yan\u0131t Mektuplar\u0131 Yay\u0131nlayarak Radikal \u015eeffafl\u0131\u011f\u0131 Benimsiyor<\/a> \u2013<\/p>","protected":false},"excerpt":{"rendered":"<p>The Food and Drug Administration published more than 200 letters it sent to companies after their medications were rejected on Thursday, drawing attention to a sometimes overlooked part of the drug review process. One of these rejection letters was sent for Vyondys 53 (golodirsen), a drug manufactured by Sarepta Therapeutics and developed for exon 53 [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":4127,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[282],"tags":[155,154,328,88,395,65,394],"class_list":["post-4111","post","type-post","status-publish","format-standard","has-post-thumbnail","category-editorials","tag-exon-53","tag-exon-53-skipping","tag-exon-53-skipping-therapy","tag-fda","tag-golodirsen","tag-sarepta","tag-vyondys-53"],"_links":{"self":[{"href":"https:\/\/dmdwarrior.com\/tr\/wp-json\/wp\/v2\/posts\/4111","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/dmdwarrior.com\/tr\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/dmdwarrior.com\/tr\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/dmdwarrior.com\/tr\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/dmdwarrior.com\/tr\/wp-json\/wp\/v2\/comments?post=4111"}],"version-history":[{"count":0,"href":"https:\/\/dmdwarrior.com\/tr\/wp-json\/wp\/v2\/posts\/4111\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/dmdwarrior.com\/tr\/wp-json\/wp\/v2\/media\/4127"}],"wp:attachment":[{"href":"https:\/\/dmdwarrior.com\/tr\/wp-json\/wp\/v2\/media?parent=4111"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/dmdwarrior.com\/tr\/wp-json\/wp\/v2\/categories?post=4111"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/dmdwarrior.com\/tr\/wp-json\/wp\/v2\/tags?post=4111"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}