Advancements in the Treatment of Transthyretin Amyloidosis

Warner AL. Advances in the treatment of transthyretin cardiac amyloidosis: Current and emerging therapies. Pharmacotherapy. 2021 Dec;41(12):1081-1091. doi: 10.1002/phar.2639. Epub 2021 Oct 30. PMID: 34669976.

Yadav JD, Othee H, Chan KA, Man DC, Belliveau PP, Towle J. Transthyretin Amyloid Cardiomyopathy-Current and Future Therapies. Ann Pharmacother. 2021 Dec;55(12):1502-1514. doi: 10.1177/10600280211000351. Epub 2021 Mar 9. PMID: 33685242.

Fine NM, Davis MK, Anderson K, Delgado DH, Giraldeau G, Kitchlu A, Massie R, Narayan J, Swiggum E, Venner CP, Ducharme A, Galant NJ, Hahn C, Howlett JG, Mielniczuk L, Parent MC, Reece D, Royal V, Toma M, Virani SA, Zieroth S. Canadian Cardiovascular Society/Canadian Heart Failure Society Joint Position Statement on the Evaluation and Management of Patients With Cardiac Amyloidosis. Can J Cardiol. 2020 Mar;36(3):322-334. doi: 10.1016/j.cjca.2019.12.034. PMID: 32145862.

Schmidt HH, Waddington-Cruz M, Botteman MF, Carter JA, Chopra AS, Hopps M, Stewart M, Fallet S, Amass L. Estimating the global prevalence of transthyretin familial amyloid polyneuropathy. Muscle Nerve. 2018 May;57(5):829-837. doi: 10.1002/mus.26034. Epub 2018 Feb 1. PMID: 29211930; PMCID: PMC5947118.

Rintell, D., Heath, D., Braga Mendendez, F. et al. Patient and family experience with transthyretin amyloid cardiomyopathy (ATTR-CM) and polyneuropathy (ATTR-PN) amyloidosis: results of two focus groups. Orphanet J Rare Dis 16, 70 (2021). https://doi.org/10.1186/s13023-021-01706-7

Pfizer. Safety and efficacy of tafamidis in patients with transthyretin cardiomyopathy (ATTR-ACT). https://clinicaltrials.gov/ct2/show/results/NCT01994889?term=Tafamidis&cond=Transthyretin Amyloid Cardiopathy&rank=2

Maurer MS, Schwartz JH, Gundapaneni B, et al. Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. N Engl J Med. 2018;379:1007-1016. doi:10.1056/NEJMoal805689

Center for Drug Evaluation and Research. Summary Review for regulatory action—NDA 211996/NDA 212161 (tafamidis meglumine/free acid). Accessed August 9, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211996Orig1s000,%20212161Orig1s000SumR.pdf

American Heart Association. What is transthyretin amyloid cardiomyopathy (ATTR-CM)? Accessed August 9, 2022. https://www.heart.org/-/media/files/health-topics/answers-by-heart/what-is-attrcm.pdf?la=en

Eidos Therapeutics. Efficacy and safety of AG10 in subjects with transthyretin amyloid cardiomyopathy (ATTRIBUTE-CM). Accessed August 9, 2022. https://clinicaltrials.gov/ct2/show/NCT03860935

Rizk M, Tüzmen Ş. Update on the clinical utility of an RNA interference-based treatment: focus on Patisiran. Pharmgenomics Pers Med. 2017 Nov 10;10:267-278. doi: 10.2147/PGPM.S87945. PMID: 29184431; PMCID: PMC5689029.

Fontana M, Martinez-Naharro A, Chacko L, Rowczenio D, Gilbertson JA, Whelan CJ, Strehina S, Lane T, Moon J, Hutt DF, Kellman P, Petrie A, Hawkins PN, Gillmore JD. Reduction in CMR Derived Extracellular Volume With Patisiran Indicates Cardiac Amyloid Regression. JACC Cardiovasc Imaging. 2021 Jan;14(1):189-199. doi: 10.1016/j.jcmg.2020.07.043. Epub 2020 Oct 28. PMID: 33129740.

Tegsedi. Package insert. Akcea Therapeutics Inc; 2019. Accessed August 9, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211172lbl.pdf

Benson MD, Waddington-Cruz M, Berk JL, Polydefkis M, Dyck PJ, Wang AK, Planté-Bordeneuve V, Barroso FA, Merlini G, Obici L, Scheinberg M, Brannagan TH 3rd, Litchy WJ, Whelan C, Drachman BM, Adams D, Heitner SB, Conceição I, Schmidt HH, Vita G, Campistol JM, Gamez J, Gorevic PD, Gane E, Shah AM, Solomon SD, Monia BP, Hughes SG, Kwoh TJ, McEvoy BW, Jung SW, Baker BF, Ackermann EJ, Gertz MA, Coelho T. Inotersen Treatment for Patients with Hereditary Transthyretin Amyloidosis. N Engl J Med. 2018 Jul 5;379(1):22-31. doi: 10.1056/NEJMoa1716793. PMID: 29972757.

Singh, Vandana. “BridgeBio Pharma Highlights Mid-Stage Study Data of ACORAMIDIS in Cardiomyopathy Trial.” Business Insider, Business Insider, 4 Apr. 2022, https://markets.businessinsider.com/news/stocks/bridgebio-pharma-highlights-mid-stage-study-data-of-acoramidis-in-cardiomyopathy-trial-1031330198.

Alnylam Pharmaceuticals. A safety and tolerability study of an investigational drug, ALN-TTRSC02, in healthy subjects. Accessed August 10, 2022. https://clinicaltrials.gov/ct2/show/NCT02797847?term=ALN-TTRSC02&draw=2

Alnylam Pharmaceuticals. “Helios-A: A Study of Vutrisiran (ALN-TTRSC02) in Patients with Hereditary Transthyretin Amyloidosis (Hattr Amyloidosis) - Full Text View.” Full Text View - ClinicalTrials.gov, 6 June 2022, https://clinicaltrials.gov/ct2/show/NCT03759379?term=NCT03759379&draw=2&rank=1.

Nicholas J. Viney, Li-Jung Tai, Shiangtung Jung, Rosie Z. Yu, Spencer Guthrie, Brenda F. Baker, Richard S. Geary, Eugene Schneider, Shuling Guo, Brett P. Monia,

Phase 1 Investigation of a Ligand-Conjugated Antisense Oligonucleotide with Increased Potency for the Treatment of Transthyretin Amyloidosis, Journal of Cardiac Failure, Volume 25, Issue 8, Supplement, 2019, Pages S80-S81, ISSN 1071-9164, https://doi.org/10.1016/j.cardfail.2019.07.228.

Ionis Pharmaceuticals Inc. CARDIO-TTRansform: a study to evaluate the efficacy and safety of AKCEA-TTR-LRx in participants with transthyretin-mediated amyloid cardiomyopathy (ATTRCM). Accessed August 10, 2022. https://clinicaltrials.gov/ct2/show/NCT04136171?lead=ionis+pharmaceuticals&phase=2&draw=2

Prothena Biosciences Limited. A study of PRX004 in subjects with amyloid transthyretin (ATTR) amyloidosis. Accessed August 11, 2022. https://clinicaltrials.gov/ct2/show/NCT03336580

Neurimmune AG. Neurimmune announces the initiation of a phase I study of NI006 for the treatment of ATTR cardiomyopathy. Accessed August 11, 2022. https://www.neurimmune.com/news/neurimmune-announces-the-initiation-of-a-phase-1-study-of-ni006-for-the-treatment-of-attr-cardiomyopathy

Coelho T, Merlini G, Bulawa CE, Fleming JA, Judge DP, Kelly JW, Maurer MS, Planté-Bordeneuve V, Labaudinière R, Mundayat R, Riley S, Lombardo I, Huertas P. Mechanism of Action and Clinical Application of Tafamidis in Hereditary Transthyretin Amyloidosis. Neurol Ther. 2016 Jun;5(1):1-25.

Arnt V Kristen, Senda Ajroud-Driss, Isabel Conceição, Peter Gorevic, Theodoros Kyriakides, Laura Obici. Patisiran, an RNAi therapeutic for the treatment of hereditary transthyretin-mediated amyloidosis. Neurodegenerative Disease Management 2019 9:1, 5-23

MedlinePlus Genetics. “What Are Genome Editing and CRISPR-Cas9?: Medlineplus Genetics.” MedlinePlus, U.S. National Library of Medicine, https://medlineplus.gov/genetics/understanding/genomicresearch/genomeediting/.

Gillmore JD, Gane E, Taubel J, Kao J, Fontana M, Maitland ML, Seitzer J, O'Connell D, Walsh KR, Wood K, Phillips J, Xu Y, Amaral A, Boyd AP, Cehelsky JE, McKee MD, Schiermeier A, Harari O, Murphy A, Kyratsous CA, Zambrowicz B, Soltys R, Gutstein DE, Leonard J, Sepp-Lorenzino L, Lebwohl D. CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis. N Engl J Med. 2021 Aug 5;385(6):493-502. doi: 10.1056/NEJMoa2107454. Epub 2021 Jun 26. PMID: 34215024.

Bennett CF. Therapeutic Antisense Oligonucleotides Are Coming of Age. Annu Rev Med. 2019 Jan 27;70:307-321. doi: 10.1146/annurev-med-041217-010829. PMID: 30691367.

Ackermann EJ, Guo S, Benson MD, Booten S, Freier S, Hughes SG, Kim TW, Jesse Kwoh T, Matson J, Norris D, Yu R, Watt A, Monia BP. Suppressing transthyretin production in mice, monkeys and humans using 2nd-Generation antisense oligonucleotides. Amyloid. 2016 Sep;23(3):148-157. doi: 10.1080/13506129.2016.1191458. Epub 2016 Jun 29. PMID: 27355239.

Gales L. Tegsedi (Inotersen): An Antisense Oligonucleotide Approved for the Treatment of Adult Patients with Hereditary Transthyretin Amyloidosis. Pharmaceuticals (Basel). 2019 May 21;12(2):78. doi: 10.3390/ph12020078. PMID: 31117178; PMCID: PMC6631675.

The Jackson Laboratory. “What Is CRISPR?” The Jackson Laboratory, 2022, https://www.jax.org/personalized-medicine/precision-medicine-and-you/what-is-crispr.

Wang H, Yang H, Shivalila CS, Dawlaty MM, Cheng AW, Zhang F, Jaenisch R (May 2013). "One-step generation of mice carrying mutations in multiple genes by CRISPR/Cas-mediated genome engineering". Cell. 153 (4): 910–8. doi:10.1016/j.cell.2013.04.025. PMC 3969854. PMID 23643243.

Lin Y, Cradick TJ, Brown MT, Deshmukh H, Ranjan P, Sarode N, Wile BM, Vertino PM, Stewart FJ, Bao G (June 2014). "CRISPR/Cas9 systems have off-target activity with insertions or deletions between target DNA and guide RNA sequences". Nucleic Acids Research. 42 (11): 7473–85. doi:10.1093/nar/gku402. PMC 4066799. PMID 24838573.

Cradick TJ, Fine EJ, Antico CJ, Bao G (November 2013). "CRISPR/Cas9 systems targeting β-globin and CCR5 genes have substantial off-target activity". Nucleic Acids Research. 41 (20): 9584–92. doi:10.1093/nar/gkt714. PMC 3814385. PMID 23939622.

Veres A, Gosis BS, Ding Q, Collins R, Ragavendran A, Brand H, Erdin S, Cowan CA, Talkowski ME, Musunuru K (July 2014). "Low incidence of off-target mutations in individual CRISPR-Cas9 and TALEN targeted human stem cell clones detected by whole-genome sequencing". Cell Stem Cell. 15 (1): 27–30. doi:10.1016/j.stem.2014.04.020. PMC 4082799. PMID 24996167.

Kim D, Bae S, Park J, Kim E, Kim S, Yu HR, Hwang J, Kim JI, Kim JS (March 2015). "Digenome-seq: genome-wide profiling of CRISPR-Cas9 off-target effects in human cells". Nature Methods. 12 (3): 237–43, 1 p following 243. doi:10.1038/nmeth.3284. PMID 25664545. S2CID 22626843.