On 2018 Jan 19, Andrea Messori commented:

Eight gene therapies are already supported by a published clinical trial

by Andrea Messori

HTA Unit, ESTAR

50135 Firenze, Italy

The study by Rangarajan and co-workers shows that gene therapies can be successful for a disease condition where the deficient factor is coded for by a very large gene. As of December 31, 2017, a published clinical trial is already available for the following 8 gene therapies:

-Voretigene neparvovec (LUXTURNA, Spark Therapeutics): trial by Russell et al 2017; approved by FDA [2].

-Tisagenlecleucel (KYMRIAH, Novartis): trial by Oncologic Drugs Advisory Committee[3]; approved by FDA [4].

-Axicabtagene ciloleucel (YESCARTA, Gilead): trial by Neelapu et al [5]; approved by FDA [6].

-STRIMVELIS (GSK): trial by Cicalese et al 2016; approved by EMA [7].

-Gene therapy with a high-specific-activity factor IX variant: trial by George et al. 2017 [9].

-Valoctocogene roxaparvovec: trial by Rangarajan et al 2017 [10].

-Single-dose gene-replacement therapy Spinal Muscular Atrophy: trial by Mendell et al 2017 [11].

-Hematopoietic stem-cell gene therapy for cerebral adrenoleukodystrophy: trial by Eichler et al 2017 [12].

References

1) Russell S, Bennett and co-workers for Cerebral Adrenoleukodystrophy J, Wellman JA, Chung DC, Yu ZF, Tillman A, Wittes J, Pappas J, Elci O, McCague S, Cross D, Marshall KA, Walshire J, Kehoe TL, Reichert H, Davis M, Raffini L, Georg Spinal Muscular Atrophy e LA, Hudson FP, Dingfield L, Zhu X, Haller JA, Sohn EH, Mahajan VB, Pfeifer W, Weckmann M, Johnson C, Gewaily D, Drack A, Stone E, Wachtel K, Simonelli F, Leroy BP, Wright JF, High KA, Maguire AM. Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial. Lancet. 2017 Aug 26;390(10097):849-860. doi: 10.1016/S0140-6736(17)31868-8.

2) FDA. FDA approves hereditary blindness gene therapy. Nat Biotechnol. 2018 Jan 10;36(1):6. doi: 10.1038/nbt0118-6a.

3) Novartis. Oncologic Drugs Advisory Committee Briefing Document. Tisagenlecleucel (CTL019) for the Treatment of Pediatric and Young Adult Patients with Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia. https://www.fda.gov/downloads/advisorycommittees /committeesmeetingmaterials/drugs /oncologicdrugsadvisorycommittee/ucm566168.pdf , July 12, 2017. Accessed September 11, 2017.

4) Bach PB, Giralt SA, Saltz LB. FDA Approval of Tisagenlecleucel: Promise and Complexities of a $475 000 Cancer Drug. JAMA. 2017 Nov 21;318(19):1861-1862. doi:10.1001/jama.2017.15218.

5) Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Ja for a totalcobson CA, Braunschweig I, Oluwole OO, Siddiqi T, Lin Y, Timmerman JM, Stiff PJ, Friedberg JW, Flinn IW, Goy A, Hill BT, Smith MR, Deol A, Farooq U, McSweeney P, Munoz J, Avivi I, Castro JE, Westin JR, Chavez JC, Ghobadi A, Komanduri KV, Levy R, Jacobsen ED, Witzig TE, Reagan P, Bot A, Rossi J, Navale L, Jiang Y, Aycock J, Elias M, Chang D, Wiezorek J, Go WY. Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. N Engl J Med. 2017 Dec 28;377(26):2531-2544. doi: 10.1056/NEJMoa1707447.

6) FDA. U.S. Food & Drug Administration. YESCARTA (axicabtagene ciloleucel), Axicabtagene Ciloleucel (YESCARTA, Gilead). https://www.fda.gov/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/ucm581222.htm

7) Cicalese MP, Ferrua F, Castagnaro L, Pajno R, Barzaghi F, Giannelli S, Dionisio F, Brigida I, Bonopane M, Casiraghi M et al. Update on the safety and efficacy of retroviral gene therapy for immunodeficiency due to adenosine deaminase deficiency. Blood 2016;128: 45 – 54.

8) Aiuti A, Roncarolo MG, Naldini L. Gene therapy for ADA-SCID, the first marketing approval of an ex vivo gene therapy in Europe: paving the road for the next generation of advanced therapy medicinal products. EMBO Mol Med. 2017 Jun;9(6):737-740. doi: 10.15252/emmm.201707573. PubMed PMID: 28396566; URL https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5452047/pdf/EMMM-9-737.pdf

9) George LA, Sullivan SK, Giermasz A, Rasko JEJ, Samelson-Jones BJ, Ducore J, Cuker A, Sullivan LM, Majumdar S, Teitel J, McGuinn CE, Ragni MV, Luk AY, Hui D, Wright JF, Chen Y, Liu Y, Wachtel K, Winters A, Tiefenbacher S, Arruda VR, van der Loo JCM, Zelenaia O, Takefman D, Carr ME, Couto LB, Anguela XM, High KA. Hemophilia B Gene Therapy with a High-Specific-Activity Factor IX Variant. N Engl J Med. 2017 Dec 7;377(23):2215-2227. doi: 10.1056/NEJMoa1708538.

10) Rangarajan S, Walsh L, Lester W, Perry D, Madan B, Laffan M, Yu H, Vettermann C, Pierce GF, Wong WY, Pasi KJ. AAV5-Factor VIII Gene Transfer in Severe Hemophilia A. N Engl J Med. 2017 Dec 28;377(26):2519-2530. doi:10.1056/NEJMoa1708483.

11) Mendell JR, Al-Zaidy S, Shell R, Arnold WD, Rodino-Klapac LR, Prior TW, Lowes L, Alfano L, Berry K, Church K, Kissel JT, Nagendran S, L'Italien J, Sproule DM, Wells C, Cardenas JA, Heitzer MD, Kaspar A, Corcoran S, Braun L, Likhite S, Miranda C, Meyer K, Foust KD, Burghes AHM, Kaspar BK. Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy. N Engl J Med. 2017 Nov 2;377(18):1713-1722. doi: 10.1056/NEJMoa1706198.

12) Eichler F, Duncan C, Musolino PL, Orchard PJ, De Oliveira S, Thrasher AJ, Armant M, Dansereau C, Lund TC, Miller WP, Raymond GV, Sankar R, Shah AJ, Sevin C, Gaspar HB, Gissen P, Amartino H, Bratkovic D, Smith NJC, Paker AM, Shamir E, O'Meara T, Davidson D, Aubourg P, Williams DA. Hematopoietic Stem-Cell Gene Therapy for Cerebral Adrenoleukodystrophy. N Engl J Med. 2017 Oct 26;377(17):1630-1638. doi: 10.1056/NEJMoa1700554.

On 2018 Jan 19, Andrea Messori commented:

Eight gene therapies are already supported by a published clinical trial

by Andrea Messori

HTA Unit, ESTAR

50135 Firenze, Italy

The study by Rangarajan and co-workers shows that gene therapies can be successful for a disease condition where the deficient factor is coded for by a very large gene. As of December 31, 2017, a published clinical trial is already available for the following 8 gene therapies:

-Voretigene neparvovec (LUXTURNA, Spark Therapeutics): trial by Russell et al 2017; approved by FDA [2].

-Tisagenlecleucel (KYMRIAH, Novartis): trial by Oncologic Drugs Advisory Committee[3]; approved by FDA [4].

-Axicabtagene ciloleucel (YESCARTA, Gilead): trial by Neelapu et al [5]; approved by FDA [6].

-STRIMVELIS (GSK): trial by Cicalese et al 2016; approved by EMA [7].

-Gene therapy with a high-specific-activity factor IX variant: trial by George et al. 2017 [9].

-Valoctocogene roxaparvovec: trial by Rangarajan et al 2017 [10].

-Single-dose gene-replacement therapy Spinal Muscular Atrophy: trial by Mendell et al 2017 [11].

-Hematopoietic stem-cell gene therapy for cerebral adrenoleukodystrophy: trial by Eichler et al 2017 [12].

References

1) Russell S, Bennett and co-workers for Cerebral Adrenoleukodystrophy J, Wellman JA, Chung DC, Yu ZF, Tillman A, Wittes J, Pappas J, Elci O, McCague S, Cross D, Marshall KA, Walshire J, Kehoe TL, Reichert H, Davis M, Raffini L, Georg Spinal Muscular Atrophy e LA, Hudson FP, Dingfield L, Zhu X, Haller JA, Sohn EH, Mahajan VB, Pfeifer W, Weckmann M, Johnson C, Gewaily D, Drack A, Stone E, Wachtel K, Simonelli F, Leroy BP, Wright JF, High KA, Maguire AM. Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial. Lancet. 2017 Aug 26;390(10097):849-860. doi: 10.1016/S0140-6736(17)31868-8.

2) FDA. FDA approves hereditary blindness gene therapy. Nat Biotechnol. 2018 Jan 10;36(1):6. doi: 10.1038/nbt0118-6a.

3) Novartis. Oncologic Drugs Advisory Committee Briefing Document. Tisagenlecleucel (CTL019) for the Treatment of Pediatric and Young Adult Patients with Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia. https://www.fda.gov/downloads/advisorycommittees /committeesmeetingmaterials/drugs /oncologicdrugsadvisorycommittee/ucm566168.pdf , July 12, 2017. Accessed September 11, 2017.

4) Bach PB, Giralt SA, Saltz LB. FDA Approval of Tisagenlecleucel: Promise and Complexities of a $475 000 Cancer Drug. JAMA. 2017 Nov 21;318(19):1861-1862. doi:10.1001/jama.2017.15218.

5) Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Ja for a totalcobson CA, Braunschweig I, Oluwole OO, Siddiqi T, Lin Y, Timmerman JM, Stiff PJ, Friedberg JW, Flinn IW, Goy A, Hill BT, Smith MR, Deol A, Farooq U, McSweeney P, Munoz J, Avivi I, Castro JE, Westin JR, Chavez JC, Ghobadi A, Komanduri KV, Levy R, Jacobsen ED, Witzig TE, Reagan P, Bot A, Rossi J, Navale L, Jiang Y, Aycock J, Elias M, Chang D, Wiezorek J, Go WY. Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. N Engl J Med. 2017 Dec 28;377(26):2531-2544. doi: 10.1056/NEJMoa1707447.

6) FDA. U.S. Food & Drug Administration. YESCARTA (axicabtagene ciloleucel), Axicabtagene Ciloleucel (YESCARTA, Gilead). https://www.fda.gov/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/ucm581222.htm

7) Cicalese MP, Ferrua F, Castagnaro L, Pajno R, Barzaghi F, Giannelli S, Dionisio F, Brigida I, Bonopane M, Casiraghi M et al. Update on the safety and efficacy of retroviral gene therapy for immunodeficiency due to adenosine deaminase deficiency. Blood 2016;128: 45 – 54.

8) Aiuti A, Roncarolo MG, Naldini L. Gene therapy for ADA-SCID, the first marketing approval of an ex vivo gene therapy in Europe: paving the road for the next generation of advanced therapy medicinal products. EMBO Mol Med. 2017 Jun;9(6):737-740. doi: 10.15252/emmm.201707573. PubMed PMID: 28396566; URL https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5452047/pdf/EMMM-9-737.pdf

9) George LA, Sullivan SK, Giermasz A, Rasko JEJ, Samelson-Jones BJ, Ducore J, Cuker A, Sullivan LM, Majumdar S, Teitel J, McGuinn CE, Ragni MV, Luk AY, Hui D, Wright JF, Chen Y, Liu Y, Wachtel K, Winters A, Tiefenbacher S, Arruda VR, van der Loo JCM, Zelenaia O, Takefman D, Carr ME, Couto LB, Anguela XM, High KA. Hemophilia B Gene Therapy with a High-Specific-Activity Factor IX Variant. N Engl J Med. 2017 Dec 7;377(23):2215-2227. doi: 10.1056/NEJMoa1708538.

10) Rangarajan S, Walsh L, Lester W, Perry D, Madan B, Laffan M, Yu H, Vettermann C, Pierce GF, Wong WY, Pasi KJ. AAV5-Factor VIII Gene Transfer in Severe Hemophilia A. N Engl J Med. 2017 Dec 28;377(26):2519-2530. doi:10.1056/NEJMoa1708483.

11) Mendell JR, Al-Zaidy S, Shell R, Arnold WD, Rodino-Klapac LR, Prior TW, Lowes L, Alfano L, Berry K, Church K, Kissel JT, Nagendran S, L'Italien J, Sproule DM, Wells C, Cardenas JA, Heitzer MD, Kaspar A, Corcoran S, Braun L, Likhite S, Miranda C, Meyer K, Foust KD, Burghes AHM, Kaspar BK. Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy. N Engl J Med. 2017 Nov 2;377(18):1713-1722. doi: 10.1056/NEJMoa1706198.

12) Eichler F, Duncan C, Musolino PL, Orchard PJ, De Oliveira S, Thrasher AJ, Armant M, Dansereau C, Lund TC, Miller WP, Raymond GV, Sankar R, Shah AJ, Sevin C, Gaspar HB, Gissen P, Amartino H, Bratkovic D, Smith NJC, Paker AM, Shamir E, O'Meara T, Davidson D, Aubourg P, Williams DA. Hematopoietic Stem-Cell Gene Therapy for Cerebral Adrenoleukodystrophy. N Engl J Med. 2017 Oct 26;377(17):1630-1638. doi: 10.1056/NEJMoa1700554.