Emerging genetic therapies for rare disorders at high cost, cannot realistically address the global burden of disease. Stakeholders must develop new pathways to ensure safe, fair and sustainable provision of such therapies

Dale, Russell

Hegde, Anaita

Idro, Richard

Kirton, Adam

Samia, Pauline

Tein, Ingrid

Tenembaum, Silvia

Topaloğlu, Haluk

Triki, Chahnez Charfi

Wilmshurst, Jo M.

English

eCommons@AKU

eCommons@AKU Paediatrics and Child Health, East Africa Medical College, East Africa 7-2019 Position Statement:Emerging genetic therapies for rare disorders Pauline Samia Adam Kirton Russell Dale Silvia Tenembaum Chahnez Charfi Triki See next page for additional authors Follow this and additional works at: https://ecommons.aku.edu/eastafrica_fhs_mc_paediatr_child_health  Part of the Pediatrics Commons Authors Pauline Samia, Adam Kirton, Russell Dale, Silvia Tenembaum, Chahnez Charfi Triki, Anaita Hegde, Richard Idro, Jo M. Wilmshurst, Ingrid Tein, and Haluk Topaloğlu LicensedunderthetermsoftheCreativeCommonsAttribution-NonCommercial-ShareAlike4.0InternationalLicence.Downloadedfromhttps://jicna.orgJICNA R©| Journal of the InternationalChild Neurology AssociationA peer reviewed open access e-journal in Child NeurologyPosition Statement:Emerging genetic therapies for rare disordersPauline Samia 1, Adam Kirton2, Russell Dale3, Silvia Tenembaum 4, Chahnez CharfiTriki 5,Anaita Hegde 6,Richard Idro7,Edward Kija 8,Jo M Wilmshurst 9,Ingrid Tein10,HalukTopaloğlu111Aga Khan University, Nairobi, Kenya; 2University of Calgary, Alberta Children’s Hospital, Canada;3The Children’s Hospital at Westmead, The University of Sydney; 4Department of Neurology,National Paediatric Hospital Dr. J.P. Garrahan Buenos Aires; 5Faculté de Médecine de Sfax,Université de Sfax, Sfax; 6Jaslok Hospital and Research Centre, Mumbai; 7Department of Pediatricsand Child Health, Makerere University College of Health Sciences; 8Muhimbili University of Healthand Allied Sciences, University of Dar es Salaam, Tanzania; 9University of Cape Town, South Africa;10University of Toronto, Canada; 11Hacettepe University School of Medicine in Ankara, Turkey.Corresponding author: Pauline Samia; Email: pauline.samia@aku.eduhttps://doi.org/10.17724/jicna.2019.172Received: 03 June 2019Accepted: 25 July 2019AbstractEmerging genetic therapies for rare disorders at high cost, cannot realistically address the global burden of disease.Stakeholders must develop new pathways to ensure safe, fair and sustainable provision of such therapies.Kewords: rare disorders, gene therapy, position statement.c© Samia P; licensee JICNAEmerging genetic therapies for raredisordersA disease or disorder is defined as rare in Europe when itaffects fewer than 1 in 2000 peopleand based on the Foodand drug admistration (FDA) definition from the US, whenit affects less than 200,000 at any one time. Genetic factorscontribute to the etiology in 80% of those with rare dis-eases, and other contributing factors, including infection,account for the remaining the cases. The recent emergenceof gene technologies has led to the development of ther-apies to treat some of the once incurable diseases. Cur-rently, there are more than 230 gene therapy efforts suchas splicing modifiers, exon skipping protocols, monoclonalantibodies, and several ‘molecular plaster’ studies. Increas-ing numbers of these therapies are being demonstrated toshow benefit and are being approved by health care author-ities leading to availability in the market [1][2][3][4].However, although these discoveries have provided thereal possibility of treatment and cure to previously con-sidered untreatable and often life-limiting diseases, at thispoint several concerns have arisen including primarily thehigh cost, access to the intervention and the potential risks[5]. These are mainly based on the following independentfactors. First, clinical studies are conducted on a narrowlydefined group with a minimal number of cases (usually lessthan 200), but the therapy is expected to be applied to amore diverse population. For example, a molecule has beenapproved by the FDA in all types of a given rare genetic dis-order, however the original study was only conducted in ba-bies less than 6 months of age [1][6]. Secondly at this timethe adverse effects portfolio in relation to these treatmentsis still accumulating, adequate data may not be available onchronic and late stage forms of disease, and uncertainitiesexist regarding long term benefits [2][3][4]. The third is-sue is related to cost regulation. These drugs are extremelyexpensive costing up to several million dollars which placesgovernmental bodies and health care providers in a diffi-cult position financially based upon the cumulative cost ofseveral hundred re-imbursements every year causing a trueburden on the health economy globally [5][7]. Last but notleast is the issue of the expectations of families which maynot match with the study end points. In other words, ‘Endpoint goals’ of patients and families in terms of clinicallyrelevant outcomes and improvements in quality of life maydiffer significantly from those included in study protocols1LicensedunderthetermsoftheCreativeCommonsAttribution-NonCommercial-ShareAlike4.0InternationalLicence.Downloadedfromhttps://jicna.orgREFERENCES REFERENCES[8].Since the 1980s there have been enormous developmentsin the whole gene therapy field which has led to significantexpectations in the community. For the time being, theseinnovative therapies act as disease modifying procedures atoften prohibitive costs. But even if they fall short of mit-igating all functional limitations in patients or eliminatingmorbidities and not fulfilling in total the families’ expecta-tions, those involved in the care of affected children con-tinue to think positively. More effective treatments may behere sooner than expected, although we are still years awayfrom definitive treatments. The cost of these interventionswill become an increasing obstacle not only for resourcepoor settings but also for resource-rich regions if the cur-rent trend is maintained. Going forward there needs to becareful consideration of the cost benefit ratio of these inter-ventions given the limited amount of resources available toprovide healthcare to the entire population.The position statement of the ICNA proposes that coun-terparts, regulators, decision makers and other party stake-holders should work in unity to address this serious globalhealth matter for vulnerable children and families. Charac-terizing these perspectives can help support decisions. Highcost is a potential barrier to accessing treatment worldwidenegating the possibility for impact for the majority of thoseafflicted.Competing interestsThe authors are not aware of any financial or non-financialcompeting interests which affect the content of this report.Authors’ contributionsThe Position Statement was compiled by Haluk Topaloğluand reviewed, adapted and endorsed by the ICNA Advo-cacy committee (Pauline Samia (chair), Adam Kirton, Rus-sell Dale, Chahnez Charfi Triki, Anaita Hedge, Helen Cross,Edward Kija, Silvia Tenembaum, Richard Idro and ICNA of-ficers Jo Wilmshurst and Ingrid Tein.This is an Open Access article distributed under theterms of the Creative Commons Attribution License(http://creativecommons.org/licenses/by/4.0), which per-mits unrestricted use, distribution, and reproduction in anymedium, provided the original work is properly credited.The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/)applies to the data made available in this article, unlessotherwise stated.Cite this article as:Samia P, Kirton A, Dale R, Tenembaum S, TrikiCC, Hegde A, Idro R, Kija E, Wilmshurst JM, TeinI, Topaloğlu H. Position Statement:Emerging ge-netic therapies for rare disorders: Genetic therapies.JICNA [Internet]. 2019Jul.25;1(1). Available from:https://jicna.org/index.php/journal/article/view/jicna-2019-172References[1] Finkel RS, Mercuri E, Darras BT, Connolly AM, KuntzNL, Kirschner J, et al. Nusinersen versus Sham Controlin Infantile-Onset Spinal Muscular Atrophy. N Engl JMed. 2017 11;377(18):1723–1732. .[2] Michelson D, Ciafaloni E, Ashwal S, Lewis E,Narayanaswami P, Oskoui M, et al. Evidence in fo-cus: Nusinersen use in spinal muscular atrophy: Reportof the Guideline Development, Dissemination, and Im-plementation Subcommittee of the American Academyof Neurology. Neurology. 2018 11;91(20):923–933..[3] Unger EF, Califf RM. Regarding "Eteplirsen for the treat-ment of Duchenne muscular dystrophy". Ann Neurol.2017 01;81(1):162–164. .[4] Groen EJN, Talbot K, Gillingwater TH. Advances intherapy for spinal muscular atrophy: promises andchallenges. Nat Rev Neurol. 2018 04;14(4):214–224..[5] Burgart AM, Magnus D, Tabor HK, Paquette ED, FraderJ, Glover JJ, et al. Ethical Challenges ConfrontedWhen Providing Nusinersen Treatment for Spinal Mus-cular Atrophy. JAMA Pediatr. 2018 Feb;172(2):188–192. .[6] Parente V, Corti S. Advances in spinal muscu-lar atrophy therapeutics. Ther Adv Neurol Disord.2018;11:1756285618754501. .[7] Shawi F, Perras C, Severn M. Emerging Drugs forDuchenne Muscular Dystrophy; 2016. .[8] Pacione M, Siskind CE, Day JW, Tabor HK. Per-spectives on Spinraza (Nusinersen) Treatment Study:Views of Individuals and Parents of Children Diagnosedwith Spinal Muscular Atrophy. J Neuromuscul Dis.2019;6(1):119–131. .2

Position Statement:Emerging genetic therapies for rare disorders

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Position Statement:Emerging genetic therapies for rare disorders

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