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خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : -45 مورد

CFTR gene mutations approved by the US Food and Drug Administration for each type of CFTR modulator therapy

CFTR gene mutations approved by the US Food and Drug Administration for each type of CFTR modulator therapy
1341G→A D565G G463V L102R Q98R S1159P
1507_1515del9 D579G G480C L1065P R1048G S1235R
1898+3A→G D614G G480S L1077P R1066C S1251N
2183A→G D836Y G551A L1324P R1066H S1255P
2752-26A→G D924N G551D L1335P R1066L S13F
2789+2insA D979V G551S L137P R1066M S341P
2789+5G→A D993Y G576A L1480P R1070Q S364P
296+28A→G E116K G576A;R668C L15P R1070W S492F
3041-15T→G E116Q G622D L165S R1162L S549I
3141del9 E193K G628R L206W R117C S549N
3195del6 E292K G85E L320V R117C;G576A;R668C S549R
3199del6 E403D G91R L333F R117G S589N
3272-26A→G E474K G970D L333H R117H S737F
3600G→A E56K G970S L346P R117L S912L
3849+10kbC→T E588V H1054D L441P R117P S945L
3849+40A→G E60K H1085P L453S R1283M S977F
3849+4A→G E822K H1085R L619S R1283S T1036N
3850-3T→G E831X H1375P L967S R170H T1053I
4005+2T→C E92K H139R L997F R258G T1086I
546insCTA F1016S H199R M1101K R297Q T1246I
5T;TG12 F1052V H199Y M1101R R31C T1299I
5T;TG13 F1074L H609R M1137V R31L T338I
621+3A→G F1099L H620P M150K R334L T351I
711+3A→G F1107L H620Q M152V R334Q T604I
A1006E F191V H939R M265R R347H V1153E
A1067P F200I H939R;H949L M952I R347L V1240G
A1067T F311del I1027T M952T R347P V1293G
A107G F311L I105N N1088D R352Q V201M
A120T F508C I1139V N1303I R352W V232D
A234D F508C;S1251N I1234Vdel6aa N1303K R516G V392G
A309D F508del* I125T N186K R516S V456A
A349V F575Y I1269N N187K R553Q V456F
A455E F587I I1366N N418S R555G V520F
A46D G1047R I1398S P140S R560S V562I
A554E G1061R I148N P205S R560T V603F
A559T G1069R I148T P499A R668C V754M
A559V G1123R I175V P574H R709Q W1098C
A561E G1244E I331N P5L R74Q W1282R
A613T G1247R I336K P67L R74W W361R
A62P G1249R I502T P750L R74W;D1270N Y1014C
A72D G126D I506L P99L R74W;V201M Y1032C
C491R G1349D I506T Q1100P R74W;V201M;D1270N Y109N
D110E G149R I556V Q1291R R751L Y161D
D110H G178E I601F Q1313K R75L Y161S
D1152H G178R I618T Q237E R75Q Y301C
D1270N G194R I807M Q237H R792G Y563N
D1445N G194V I980K Q359R R933G Y569C
D192G G27E K1060T Q372H S1045Y Y913C
D443Y G27R K162E Q452P S108F  
D443Y;G576A;R668C G314E K464E Q493R S1118F
D513G G424S L1011S Q552P S1159F
 
Color key:[1-4]
  Approved for VTD and ETI (118 mutations)
  Approved for VTD, ETI, Tez-Iva, and Iva (97 mutations)
  Approved for VTD, ETI, and Tez-Iva [but not Iva] (57 mutations)
  Approved for VTD only (31 mutations)

A person with CF confirmed by sweat testing and/or genotyping is eligible for VTD if they have 1 or more of the above mutations. In general, if a patient has a genotype that is eligible for more than 1 therapy, we suggest starting on the maximal therapy available for their age group (ie, triple therapy > dual therapy > monotherapy). As of December 2024, the US Food and Drug Administration has approved IVA for children ≥1 month, Lum-Iva for ≥1 year, ETI for ≥2 years, and VTD and Tez-Iva for ≥6 years[1-5].

Indications for ETI are somewhat different in Europe. In March 2025, the European Medicines Agency expanded the indications for ETI (Kaftrio) to include people with CF age ≥2 years who have at least 1 nonclass I CFTR mutation (refer to UpToDate content on genetics of CF)[6]. This includes all of the genotypes approved for ETI in the United States as listed above, plus some additional nonclass I CFTR mutations.

CF: cystic fibrosis; CFTR: cystic fibrosis transmembrane conductance regulator; ETI: elexacaftor-tezacaftor-ivacaftor; Iva: ivacaftor; Lum-Iva: lumacaftor-ivacaftor; Tez-Iva: tezacaftor-ivacaftor; VTD: vanzacaftor-tezacaftor-deutivacaftor.

* F508del is the most common CFTR gene mutation in most populations. Drug eligibility considerations are:

  • F508del heterozygotes – F508del heterozygotes are eligible for ETI or VTD regardless of the mutation at the other allele. To be eligible for Tez-Iva, the mutation at the other allele must be listed as responsive to this drug.
  • F508del homozygotes – F508del homozygotes are eligible for several drug combinations, including VTD, ETI, Tez-Iva, and Lum-Iva. We recommend triple therapy (ETI or VTD) rather than dual therapy (Tez-Iva or Lum-Iva) as soon as they reach an eligible age (ETI at age ≥2 years; VTD at age ≥6 years). We suggest Lum-Iva for children ages ≥1 to <2 years.
Prepared with data from:
  1. ALYFTREK® (vanzacaftor, tezacaftor, and deutivacaftor tablets). Revised December 2024. Vertex Pharmaceuticals Incorporated. https://pi.vrtx.com/files/uspi_vanzacaftor_tezacaftor_deutivacaftor.pdf (Accessed on January 14, 2025).
  2. TRIKAFTA® (elexacaftor/tezacaftor/ivacaftor; ivacaftor tablets and oral granules). Revised December 2024. Vertex Pharmaceuticals Incorporated. https://pi.vrtx.com/files/uspi_elexacaftor_tezacaftor_ivacaftor.pdf (Accessed on January 14, 2025).
  3. SYMDEKO® (tezacaftor/ivacaftor; ivacaftor tablets). Revised August 2023. Vertex Pharmaceuticals Incorporated. https://pi.vrtx.com/files/uspi_tezacaftor_ivacaftor.pdf (Accessed on January 14, 2025).
  4. ORKAMBI® (lumacaftor/ivacaftor; ivacaftor tablets). Revised December 2024. Vertex Pharmaceuticals Incorporated. https://pi.vrtx.com/files/uspi_lumacaftor_ivacaftor.pdf (Accessed on January 14, 2025).
  5. KALYDECO® (ivacaftor tablets and oral granules). Revised August 2023. Vertex Pharmaceuticals Incorporated. https://pi.vrtx.com/files/uspi_ivacaftor.pdf (Accessed on January 14, 2025).
  6. European Medicines Agency. Kaftrio - opinion on variation to marketing authorization. https://www.ema.europa.eu/en/medicines/human/variation/kaftrio-0 (Accessed on March 5, 2025).
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