Fletcher, Elaine

Gillingwater, Thomas H.

Hamilton, Mark

Horrocks, Iain

McWilliam, Catherine

McWilliam, Kenneth

Parson, Simon H.

Smith, Sarah

Williams, Nicola

Scottish Medical Journal

English

Gillingwater, Thomas H

Horrocks, Ian

Edinburgh Research Explorer

     Edinburgh Research Explorer                                      A call to introduce newborn screening for spinal muscularatrophy (SMA) in ScotlandCitation for published version:Gillingwater, TH, McWilliam, C, Horrocks, I, McWilliam, K, Hamilton, M, Fletcher, E, Williams, N, Smith, S &Parson, SH 2022, 'A call to introduce newborn screening for spinal muscular atrophy (SMA) in Scotland',Scottish Medical Journal, vol. 67, no. 1, pp. 46-47. https://doi.org/10.1177/00369330221078994Digital Object Identifier (DOI):10.1177/00369330221078994Link:Link to publication record in Edinburgh Research ExplorerDocument Version:Peer reviewed versionPublished In:Scottish Medical JournalGeneral rightsCopyright for the publications made accessible via the Edinburgh Research Explorer is retained by the author(s)and / or other copyright owners and it is a condition of accessing these publications that users recognise andabide by the legal requirements associated with these rights.Take down policyThe University of Edinburgh has made every reasonable effort to ensure that Edinburgh Research Explorercontent complies with UK legislation. If you believe that the public display of this file breaches copyright pleasecontact openaccess@ed.ac.uk providing details, and we will remove access to the work immediately andinvestigate your claim.Download date: 27. Oct. 2022A call to introduce newborn screening for spinal muscular atrophy (SMA) in Scotland  The recent development of three effective therapies for patients with spinal muscular atrophy (SMA) – Nusinersen (Spinraza), Onasemnogene abeparvovec (Zolgensma) and Risdiplam (Evrysdi) - arguably represents one of the great medical achievements of the 21st century1. These treatments, which all work via restoring levels of the SMN protein, have revolutionised the outlook for patients with an otherwise incurable, and mostly fatal, condition. However, all three treatments come at a significant financial cost. For example, Zolgensma (often referred to as “the world’s most expensive drug”) has a list price of nearly £1.8m per dose. Moreover, a large body of pre-clinical research, supported by emerging data from patient clinical trials, makes clear that the effectiveness of all current SMA therapies is largely determined by how early therapy can be delivered1,2. Thus, pre-symptomatic treatment of patients results in significantly better outcomes - both in terms of patient benefits and financial return on investment - than starting treatment after symptom onset.  If pre-symptomatic treatment is a key determinant of success, then it follows that any possibility to identify SMA patients before the onset of symptoms, and hence begin treatment as early as possible, should be taken advantage of. Importantly, just such an opportunity already exists: newborn screening (NBS) to identify genetic defects underlying disease. At present, NBS programmes in the UK routinely screen for conditions such as cystic fibrosis and congenital hypothyroidism, but not SMA. However, NBS for SMA has already been successfully introduced in many other countries. For example, SMA is now included in the Recommended Uniform Screening Panel (RUSP) from the US Department of Health and Human Services3. Likewise, the recent ‘Sun May Arise on SMA’ pilot NBS programme in Belgium led to the official adoption of NBS in Southern Belgium in March 2021, with Northern Belgium including SMA in their official program from 20224. Emerging data from these real-world scenarios confirm that NBS for SMA is both robust and reliable, whilst also representing value for money5.   Recent approvals from the Scottish Medicines Consortium mean that patients with SMA in Scotland now have access to therapies. Importantly, approval has also been given (at least for Zolgensma) for SMA patients in Scotland to receive treatment pre-symptomatically. However, while NICE has recommended use of Zolgensma for presymptomatic use in SMA, this is under a Managed Access Agreement, which leaves financial responsibility for provision of the drug with the drug company and provision of this at the drug company’s discretion. This lack of approved pre-symptomatic treatment is one reason provided by the UK National Screening Committee for not approving NBS for SMA at the UK-wide level. However, the availability of pre-symptomatic treatment for SMA in Scotland leads to a situation whereby Scottish SMA patients and their families are being denied the possibility of accessing NBS, and potentially much better clinical outcomes, due to decisions being taken and applied at the UK-wide level.  NBS does not come without important ethical, societal and financial implications6. There are myriad reasons why NBS is not suitable for many genetic conditions at present. However, as professionals involved in SMA research, diagnosis and patient care in Scotland, we believe that all of the necessary data, evidence, and therapeutic approvals are in place to justify the inclusion of SMA on NBS programmes in Scotland. The inclusion of NBS for SMA would provide the best possible quality of life for SMA patients and their families, whilst maximising the (not insignificant) return on investment that society makes in providing access to SMN-restoring therapies7.  References: 1. Chaytow H, Faller KME, Huang YT, Gillingwater TH. (2021) Spinal muscular atrophy: From approved therapies to future therapeutic targets for personalized medicine. Cell Rep Med. 2(7):100346. 2. De Vivo DC, Bertini E, Swoboda KJ, Hwu WL, Crawford TO, Finkel RS, Kirschner J, Kuntz NL, Parsons JA, Ryan MM, Butterfield RJ, Topaloglu H, Ben-Omran T, Sansone VA, Jong YJ, Shu F, Staropoli JF, Kerr D, Sandrock AW, Stebbins C, Petrillo M, Braley G, Johnson K, Foster R, Gheuens S, Bhan I, Reyna SP, Fradette S, Farwell W; NURTURE Study Group. (2019) Nusinersen initiated in infants during the presymptomatic stage of spinal muscular atrophy: Interim efficacy and safety results from the Phase 2 NURTURE study. Neuromuscul Disord. 29(11):842-856. 3. Kay DM, Stevens CF, Parker A, Saavedra-Matiz CA, Sack V, Chung WK, Chiriboga CA, Engelstad K, Laureta E, Farooq O, Ciafaloni E, Lee BH, Malek S, Treidler S, Anziska Y, Delfiner L, Sakonju A, Caggana M. (2020) Implementation of population-based newborn screening reveals low incidence of spinal muscular atrophy. Genet Med. 22(8):1296-1302. 4. Boemer F, Caberg JH, Beckers P, Dideberg V, di Fiore S, Bours V, Marie S, Dewulf J, Marcelis L, Deconinck N, Daron A, Blasco-Perez L, Tizzano E, Hiligsmann M, Lombet J, Pereira T, Lopez-Granados L, Shalchian-Tehran S, van Assche V, Willems A, Huybrechts S, Mast B, van Olden R, Dangouloff T, Servais L. (2021) Three years pilot of spinal muscular atrophy newborn screening turned into official program in Southern Belgium. Sci Rep. 11(1):19922. 5. Gillingwater TH. (2021) Maximising returns: combining newborn screening with gene therapy for spinal muscular atrophy. J Neurol Neurosurg Psychiatry. In press: jnnp-2021-327459. 6. Esquerda M, Palau F, Lorenzo D, Cambra FJ, Bofarull M, Cusi V, Interdisciplinar En Bioetica G. (2021) Ethical questions concerning newborn genetic screening. Clin Genet. 99(1):93-98. 7. European Alliance for Newborn Screening in SMA (2021) Whitepaper - Spinal muscular atrophy: screen at birth, save lives (version 1, 26 March 2021). https://www.sma-screening-alliance.org/tools/ Accessed 17 November 2021.  Authors: Thomas H. Gillingwater is Professor of Anatomy and an SMA researcher at the University of Edinburgh. He is Chair-Elect of the Clinical & Scientific Advisory Board of SMA Europe.  Catherine McWilliam is a Clinical Geneticist with an interest in neuromuscular disease, based in NHS Tayside. She is Lead Clinician for the Scottish Muscle Network.  Iain Horrocks is a Paediatric Neurologist and lead of the West of Scotland Neuromuscular service delivering Gene Therapy in Scotland.  Kenneth McWilliam is a Paediatric Neurologist and Chair of Scottish Paediatric Neurology Group  Mark Hamilton is a Clinical Geneticist based in the West of Scotland, and member of the Scottish Muscle Network.  Elaine Fletcher is a Clinical Geneticist based in the South East of Scotland, and member of the Scottish Muscle Network  Nicola Williams is a Consultant Clinical Scientist and Head of Service, West of Scotland Centre for Genomic Medicine  Simon H. Parson is Regius Professor of Anatomy and an SMA researcher at the University of Aberdeen.   Sarah Smith is a Consultant Clinical Scientist and Director of the Scottish Newborn Screening Laboratory.   Declaration of Interests: THG has served on SMA global advisory boards for Roche. IH has served on SMA global advisory boards for Roche, Novartis and Biogen. KM has served on SMA advisory boards for Roche and Novartis.  

A call to introduce newborn screening for spinal muscular atrophy (SMA) in Scotland

Discovery Research Portal

                                                                    University of DundeeA call to introduce newborn screening for spinal muscular atrophy (SMA) in ScotlandGillingwater, Thomas H.; McWilliam, Catherine; Horrocks, Iain; McWilliam, Kenneth;Hamilton, Mark; Fletcher, ElainePublished in:Scottish Medical JournalDOI:10.1177/00369330221078994Publication date:2022Licence:CC BY-NC-NDDocument VersionPublisher's PDF, also known as Version of recordLink to publication in Discovery Research PortalCitation for published version (APA):Gillingwater, T. H., McWilliam, C., Horrocks, I., McWilliam, K., Hamilton, M., Fletcher, E., Williams, N., Smith, S.,& Parson, S. H. (2022). A call to introduce newborn screening for spinal muscular atrophy (SMA) in Scotland.Scottish Medical Journal. https://doi.org/10.1177/00369330221078994General rightsCopyright and moral rights for the publications made accessible in Discovery Research Portal are retained by the authors and/or othercopyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated withthese rights. • Users may download and print one copy of any publication from Discovery Research Portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain. • You may freely distribute the URL identifying the publication in the public portal.Take down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Download date: 24. Apr. 2022A call to introduce newborn screening forspinal muscular atrophy (SMA) in ScotlandThomas H. Gillingwater1 , Catherine McWilliam2,Iain Horrocks3, Kenneth McWilliam4, Mark Hamilton3,Elaine Fletcher4, Nicola Williams3, Sarah Smith3and Simon H. Parson5The recent development of three effective therapies forpatients with spinal muscular atrophy (SMA) – Nusinersen(Spinraza), Onasemnogene abeparvovec (Zolgensma) andRisdiplam (Evrysdi) - arguably represents one of the greatmedical achievements of the 21st century.1 These treatments,which all work via restoring levels of the SMN protein,have revolutionised the outlook for patients with an otherwiseincurable, andmostly fatal, condition. However, all three treat-ments come at a significant financial cost For example,Zolgensma (often referred to as “the world’s most expensivedrug”) has a list price of nearly £1.8m per dose. Moreover,a large body of pre-clinical research, supported by emergingdata from patient clinical trials, makes clear that the effective-ness of all current SMA therapies is largely determined byhow early therapy can be delivered.1,2 Thus, pre-symptomatictreatment of patients results in significantly better outcomes -both in terms of patient benefits and financial return on invest-ment - than starting treatment after symptom onset.If pre-symptomatic treatment is a key determinant ofsuccess, then it follows that any possibility to identifySMA patients before the onset of symptoms, and hencebegin treatment as early as possible, should be taken advan-tage of. Importantly, just such an opportunity already exists:newborn screening (NBS) to identify genetic defects under-lying disease. At present, NBS programmes in the UK rou-tinely screen for conditions such as cystic fibrosis andcongenital hypothyroidism, but not SMA. However, NBSfor SMA has already been successfully introduced inmany other countries. For example, SMA is now includedin the Recommended Uniform Screening Panel (RUSP)from the US Department of Health and Human Services.3Likewise, the recent ‘Sun May Arise on SMA’ pilot NBSprogramme in Belgium led to the official adoption of NBSin Southern Belgium in March 2021, with Northern Belgiumincluding SMA in their official program from 2022.4Emerging data from these real-world scenarios confirmthat NBS for SMA is both robust and reliable, whilst alsorepresenting value for money.5Recent approvals from the Scottish Medicines Consortiummean that patients with SMA in Scotland now have access totherapies. Importantly, approval has also been given (at leastfor Zolgensma) for SMA patients in Scotland to receive treat-ment pre-symptomatically. However, while NICE has recom-mended use of Zolgensma for presymptomatic use in SMA,this is under a Managed Access Agreement and thereforenot considered routine care. This lack of approved pre-symptomatic treatment is one reason provided by the UKNational Screening Committee for not approving NBS forSMA at the UK-wide level. However, the availability of pre-symptomatic treatment for SMA in Scotland leads to a situa-tion whereby Scottish SMA patients and their families arebeing denied the possibility of accessing NBS, and potentiallymuch better clinical outcomes, due to decisions being takenand applied at the UK-wide level.NBS does not come without important ethical, societaland financial implications.6 There are myriad reasons whyNBS is not suitable for many genetic conditions atpresent. However, as professionals involved in SMAresearch, diagnosis and patient care in Scotland, webelieve that all of the necessary data, evidence, and thera-peutic approvals are in place to justify the inclusion ofSMA on NBS programmes in Scotland. The inclusion ofNBS for SMA would provide the best possible quality oflife for SMA patients and their families, whilst maximisingthe (not insignificant) return on investment that societymakes in providing access to SMN-restoring therapies.7Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respectto the research, authorship, and/or publication of this article.1Edinburgh Medical School: Biomedical Sciences, The University ofEdinburgh, Edinburgh, UK2NHS Tayside, Dundee, UK3NHS Greater Glasgow and Clyde, Glasgow, UK4NHS Lothian, Edinburgh, UK5University of Aberdeen, Aberdeen, UKCorresponding author:Thomas H. Gillingwater, Edinburgh Medical School: Biomedical Sciences,The University of Edinburgh, Old Medical School (Anatomy), Teviot Place,Edinburgh, EH8 9YL, UK.Email: t.gillingwater@ed.ac.ukLetterScottish Medical Journal1–2© The Author(s) 2022Article reuse guidelines:sagepub.com/journals-permissionsDOI: 10.1177/00369330221078994journals.sagepub.com/home/scmFundingThe author(s) received no financial support for the research,authorship, and/or publication of this article.Declaration of InterestsTHG has served on SMA global advisory boards for Roche. IH hasserved on SMA global advisory boards for Roche, Novartis andBiogen. KM has served on SMA advisory boards for Roche andNovartis.ORCID iDThomas H. Gillingwater https://orcid.org/0000-0002-0306-5577References1. Chaytow H, Faller KME, Huang YT, et al. Spinal muscularatrophy: from approved therapies to future therapeutic targetsfor personalized medicine. Cell Rep Med 2021; 2: 100346.2. De Vivo DC, Bertini E, Swoboda KJ, et al. Nusinersen initiatedin infants during the presymptomatic stage of spinal muscularatrophy: interim efficacy and safety results from the phase 2NURTURE study. Neuromuscul Disord 2019; 29: 842–856.3. Kay DM, Stevens CF, Parker A, et al. Implementation ofpopulation-based newborn screening reveals low incidence ofspinal muscular atrophy. Genet Med 2020; 22: 1296–1302.4. Boemer F, Caberg JH, Beckers P, et al. Three years pilot ofspinal muscular atrophy newborn screening turned into officialprogram in southern Belgium. Sci Rep 2021; 11: 19922.5. Gillingwater TH. Maximising returns: combining newbornscreening with gene therapy for spinal muscular atrophy.J Neurol Neurosurg Psychiatry 2021; 92: 1252.6. Esquerda M, Palau F, Lorenzo D, et al. Ethical questions concern-ing newborn genetic screening. Clin Genet 2021; 99: 93–98.7. European Alliance for Newborn Screening in SMA. Whitepaper -Spinal muscular atrophy: screen at birth, save lives (version 1, 26March 2021). https://www.sma-screening-alliance.org/tools/Accessed 17 November 2021. 2021.2 Scottish Medical Journal 0(0)

Parson, Simon

Aberdeen University Research

A call to introduce newborn screening forspinal muscular atrophy (SMA) in ScotlandThomas H. Gillingwater1 , Catherine McWilliam2,Iain Horrocks3, Kenneth McWilliam4, Mark Hamilton3,Elaine Fletcher4, Nicola Williams3, Sarah Smith3and Simon H. Parson5The recent development of three effective therapies forpatients with spinal muscular atrophy (SMA) – Nusinersen(Spinraza), Onasemnogene abeparvovec (Zolgensma) andRisdiplam (Evrysdi) - arguably represents one of the greatmedical achievements of the 21st century.1 These treatments,which all work via restoring levels of the SMN protein,have revolutionised the outlook for patients with an otherwiseincurable, andmostly fatal, condition. However, all three treat-ments come at a significant financial cost For example,Zolgensma (often referred to as “the world’s most expensivedrug”) has a list price of nearly £1.8m per dose. Moreover,a large body of pre-clinical research, supported by emergingdata from patient clinical trials, makes clear that the effective-ness of all current SMA therapies is largely determined byhow early therapy can be delivered.1,2 Thus, pre-symptomatictreatment of patients results in significantly better outcomes -both in terms of patient benefits and financial return on invest-ment - than starting treatment after symptom onset.If pre-symptomatic treatment is a key determinant ofsuccess, then it follows that any possibility to identifySMA patients before the onset of symptoms, and hencebegin treatment as early as possible, should be taken advan-tage of. Importantly, just such an opportunity already exists:newborn screening (NBS) to identify genetic defects under-lying disease. At present, NBS programmes in the UK rou-tinely screen for conditions such as cystic fibrosis andcongenital hypothyroidism, but not SMA. However, NBSfor SMA has already been successfully introduced inmany other countries. For example, SMA is now includedin the Recommended Uniform Screening Panel (RUSP)from the US Department of Health and Human Services.3Likewise, the recent ‘Sun May Arise on SMA’ pilot NBSprogramme in Belgium led to the official adoption of NBSin Southern Belgium in March 2021, with Northern Belgiumincluding SMA in their official program from 2022.4Emerging data from these real-world scenarios confirmthat NBS for SMA is both robust and reliable, whilst alsorepresenting value for money.5Recent approvals from the Scottish Medicines Consortiummean that patients with SMA in Scotland now have access totherapies. Importantly, approval has also been given (at leastfor Zolgensma) for SMA patients in Scotland to receive treat-ment pre-symptomatically. However, while NICE has recom-mended use of Zolgensma for presymptomatic use in SMA,this is under a Managed Access Agreement and thereforenot considered routine care. This lack of approved pre-symptomatic treatment is one reason provided by the UKNational Screening Committee for not approving NBS forSMA at the UK-wide level. However, the availability of pre-symptomatic treatment for SMA in Scotland leads to a situ-ation whereby Scottish SMA patients and their families arebeing denied the possibility of accessing NBS, and potentiallymuch better clinical outcomes, due to decisions being takenand applied at the UK-wide level.NBS does not come without important ethical, societaland financial implications.6 There are myriad reasons whyNBS is not suitable for many genetic conditions atpresent. However, as professionals involved in SMAresearch, diagnosis and patient care in Scotland, webelieve that all of the necessary data, evidence, and thera-peutic approvals are in place to justify the inclusion ofSMA on NBS programmes in Scotland. The inclusion ofNBS for SMA would provide the best possible quality oflife for SMA patients and their families, whilst maximisingthe (not insignificant) return on investment that societymakes in providing access to SMN-restoring therapies.7Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respectto the research, authorship, and/or publication of this article.1Edinburgh Medical School: Biomedical Sciences, The University ofEdinburgh, Edinburgh, UK2NHS Tayside, Dundee, UK3NHS Greater Glasgow and Clyde, Glasgow, UK4NHS Lothian, Edinburgh, UK5University of Aberdeen, Aberdeen, UKCorresponding author:Thomas H. Gillingwater, Edinburgh Medical School: Biomedical Sciences,The University of Edinburgh, Old Medical School (Anatomy), Teviot Place,Edinburgh, EH8 9YL, UK.Email: t.gillingwater@ed.ac.ukLetterScottish Medical Journal2022, Vol. 67(1) 46–47© The Author(s) 2022Article reuse guidelines:sagepub.com/journals-permissionsDOI: 10.1177/00369330221078994journals.sagepub.com/home/scmFundingThe author(s) received no financial support for the research,authorship, and/or publication of this article.Declaration of InterestsTHG has served on SMA global advisory boards for Roche. IH hasserved on SMA global advisory boards for Roche, Novartis andBiogen. KM has served on SMA advisory boards for Roche andNovartis.ORCID iDThomas H. Gillingwater https://orcid.org/0000-0002-0306-5577References1. Chaytow H, Faller KME, Huang YT, et al. Spinal muscularatrophy: from approved therapies to future therapeutic targetsfor personalized medicine. Cell Rep Med 2021; 2: 100346.2. De Vivo DC, Bertini E, Swoboda KJ, et al. Nusinersen initiatedin infants during the presymptomatic stage of spinal muscularatrophy: interim efficacy and safety results from the phase 2NURTURE study. Neuromuscul Disord 2019; 29: 842–856.3. Kay DM, Stevens CF, Parker A, et al. Implementation ofpopulation-based newborn screening reveals low incidence ofspinal muscular atrophy. Genet Med 2020; 22: 1296–1302.4. Boemer F, Caberg JH, Beckers P, et al. Three years pilot ofspinal muscular atrophy newborn screening turned into officialprogram in southern Belgium. Sci Rep 2021; 11: 19922.5. Gillingwater TH. Maximising returns: combining newbornscreening with gene therapy for spinal muscular atrophy.J Neurol Neurosurg Psychiatry 2021; 92: 1252.6. Esquerda M, Palau F, Lorenzo D, et al. Ethical questions concern-ing newborn genetic screening. Clin Genet 2021; 99: 93–98.7. European Alliance for Newborn Screening in SMA. Whitepaper -Spinal muscular atrophy: screen at birth, save lives (version 1, 26March 2021). https://www.sma-screening-alliance.org/tools/Accessed 17 November 2021. 2021.Gillingwater et al. 47

                                                                    University of DundeeA call to introduce newborn screening for spinal muscular atrophy (SMA) in ScotlandGillingwater, Thomas H.; McWilliam, Catherine; Horrocks, Iain; McWilliam, Kenneth;Hamilton, Mark; Fletcher, ElainePublished in:Scottish Medical JournalDOI:10.1177/00369330221078994Publication date:2022Licence:CC BY-NC-NDDocument VersionPublisher's PDF, also known as Version of recordLink to publication in Discovery Research PortalCitation for published version (APA):Gillingwater, T. H., McWilliam, C., Horrocks, I., McWilliam, K., Hamilton, M., Fletcher, E., Williams, N., Smith, S.,& Parson, S. H. (2022). A call to introduce newborn screening for spinal muscular atrophy (SMA) in Scotland.Scottish Medical Journal, 67(1), 46-47. https://doi.org/10.1177/00369330221078994General rightsCopyright and moral rights for the publications made accessible in Discovery Research Portal are retained by the authors and/or othercopyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated withthese rights.Take down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Download date: 25. Sep. 2025A call to introduce newborn screening forspinal muscular atrophy (SMA) in ScotlandThomas H. Gillingwater1 , Catherine McWilliam2,Iain Horrocks3, Kenneth McWilliam4, Mark Hamilton3,Elaine Fletcher4, Nicola Williams3, Sarah Smith3and Simon H. Parson5The recent development of three effective therapies forpatients with spinal muscular atrophy (SMA) – Nusinersen(Spinraza), Onasemnogene abeparvovec (Zolgensma) andRisdiplam (Evrysdi) - arguably represents one of the greatmedical achievements of the 21st century.1 These treatments,which all work via restoring levels of the SMN protein,have revolutionised the outlook for patients with an otherwiseincurable, andmostly fatal, condition. However, all three treat-ments come at a significant financial cost For example,Zolgensma (often referred to as “the world’s most expensivedrug”) has a list price of nearly £1.8m per dose. Moreover,a large body of pre-clinical research, supported by emergingdata from patient clinical trials, makes clear that the effective-ness of all current SMA therapies is largely determined byhow early therapy can be delivered.1,2 Thus, pre-symptomatictreatment of patients results in significantly better outcomes -both in terms of patient benefits and financial return on invest-ment - than starting treatment after symptom onset.If pre-symptomatic treatment is a key determinant ofsuccess, then it follows that any possibility to identifySMA patients before the onset of symptoms, and hencebegin treatment as early as possible, should be taken advan-tage of. Importantly, just such an opportunity already exists:newborn screening (NBS) to identify genetic defects under-lying disease. At present, NBS programmes in the UK rou-tinely screen for conditions such as cystic fibrosis andcongenital hypothyroidism, but not SMA. However, NBSfor SMA has already been successfully introduced inmany other countries. For example, SMA is now includedin the Recommended Uniform Screening Panel (RUSP)from the US Department of Health and Human Services.3Likewise, the recent ‘Sun May Arise on SMA’ pilot NBSprogramme in Belgium led to the official adoption of NBSin Southern Belgium in March 2021, with Northern Belgiumincluding SMA in their official program from 2022.4Emerging data from these real-world scenarios confirmthat NBS for SMA is both robust and reliable, whilst alsorepresenting value for money.5Recent approvals from the Scottish Medicines Consortiummean that patients with SMA in Scotland now have access totherapies. Importantly, approval has also been given (at leastfor Zolgensma) for SMA patients in Scotland to receive treat-ment pre-symptomatically. However, while NICE has recom-mended use of Zolgensma for presymptomatic use in SMA,this is under a Managed Access Agreement and thereforenot considered routine care. This lack of approved pre-symptomatic treatment is one reason provided by the UKNational Screening Committee for not approving NBS forSMA at the UK-wide level. However, the availability of pre-symptomatic treatment for SMA in Scotland leads to a situa-tion whereby Scottish SMA patients and their families arebeing denied the possibility of accessing NBS, and potentiallymuch better clinical outcomes, due to decisions being takenand applied at the UK-wide level.NBS does not come without important ethical, societaland financial implications.6 There are myriad reasons whyNBS is not suitable for many genetic conditions atpresent. However, as professionals involved in SMAresearch, diagnosis and patient care in Scotland, webelieve that all of the necessary data, evidence, and thera-peutic approvals are in place to justify the inclusion ofSMA on NBS programmes in Scotland. The inclusion ofNBS for SMA would provide the best possible quality oflife for SMA patients and their families, whilst maximisingthe (not insignificant) return on investment that societymakes in providing access to SMN-restoring therapies.7Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respectto the research, authorship, and/or publication of this article.1Edinburgh Medical School: Biomedical Sciences, The University ofEdinburgh, Edinburgh, UK2NHS Tayside, Dundee, UK3NHS Greater Glasgow and Clyde, Glasgow, UK4NHS Lothian, Edinburgh, UK5University of Aberdeen, Aberdeen, UKCorresponding author:Thomas H. Gillingwater, Edinburgh Medical School: Biomedical Sciences,The University of Edinburgh, Old Medical School (Anatomy), Teviot Place,Edinburgh, EH8 9YL, UK.Email: t.gillingwater@ed.ac.ukLetterScottish Medical Journal1–2© The Author(s) 2022Article reuse guidelines:sagepub.com/journals-permissionsDOI: 10.1177/00369330221078994journals.sagepub.com/home/scmFundingThe author(s) received no financial support for the research,authorship, and/or publication of this article.Declaration of InterestsTHG has served on SMA global advisory boards for Roche. IH hasserved on SMA global advisory boards for Roche, Novartis andBiogen. KM has served on SMA advisory boards for Roche andNovartis.ORCID iDThomas H. Gillingwater https://orcid.org/0000-0002-0306-5577References1. Chaytow H, Faller KME, Huang YT, et al. Spinal muscularatrophy: from approved therapies to future therapeutic targetsfor personalized medicine. Cell Rep Med 2021; 2: 100346.2. De Vivo DC, Bertini E, Swoboda KJ, et al. Nusinersen initiatedin infants during the presymptomatic stage of spinal muscularatrophy: interim efficacy and safety results from the phase 2NURTURE study. Neuromuscul Disord 2019; 29: 842–856.3. Kay DM, Stevens CF, Parker A, et al. Implementation ofpopulation-based newborn screening reveals low incidence ofspinal muscular atrophy. Genet Med 2020; 22: 1296–1302.4. Boemer F, Caberg JH, Beckers P, et al. Three years pilot ofspinal muscular atrophy newborn screening turned into officialprogram in southern Belgium. Sci Rep 2021; 11: 19922.5. Gillingwater TH. Maximising returns: combining newbornscreening with gene therapy for spinal muscular atrophy.J Neurol Neurosurg Psychiatry 2021; 92: 1252.6. Esquerda M, Palau F, Lorenzo D, et al. Ethical questions concern-ing newborn genetic screening. Clin Genet 2021; 99: 93–98.7. European Alliance for Newborn Screening in SMA. Whitepaper -Spinal muscular atrophy: screen at birth, save lives (version 1, 26March 2021). https://www.sma-screening-alliance.org/tools/Accessed 17 November 2021. 2021.2 Scottish Medical Journal 0(0)

                                                                    University of DundeeA call to introduce newborn screening for spinal muscular atrophy (SMA) in ScotlandGillingwater, Thomas H.; McWilliam, Catherine; Horrocks, Iain; McWilliam, Kenneth;Hamilton, Mark; Fletcher, ElainePublished in:Scottish Medical JournalDOI:10.1177/00369330221078994Publication date:2022Licence:CC BY-NC-NDDocument VersionPublisher's PDF, also known as Version of recordLink to publication in Discovery Research PortalCitation for published version (APA):Gillingwater, T. H., McWilliam, C., Horrocks, I., McWilliam, K., Hamilton, M., Fletcher, E., Williams, N., Smith, S.,& Parson, S. H. (2022). A call to introduce newborn screening for spinal muscular atrophy (SMA) in Scotland.Scottish Medical Journal, 67(1), 46-47. https://doi.org/10.1177/00369330221078994General rightsCopyright and moral rights for the publications made accessible in Discovery Research Portal are retained by the authors and/or othercopyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated withthese rights. • Users may download and print one copy of any publication from Discovery Research Portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain. • You may freely distribute the URL identifying the publication in the public portal.Take down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Download date: 19. Apr. 2023A call to introduce newborn screening forspinal muscular atrophy (SMA) in ScotlandThomas H. Gillingwater1 , Catherine McWilliam2,Iain Horrocks3, Kenneth McWilliam4, Mark Hamilton3,Elaine Fletcher4, Nicola Williams3, Sarah Smith3and Simon H. Parson5The recent development of three effective therapies forpatients with spinal muscular atrophy (SMA) – Nusinersen(Spinraza), Onasemnogene abeparvovec (Zolgensma) andRisdiplam (Evrysdi) - arguably represents one of the greatmedical achievements of the 21st century.1 These treatments,which all work via restoring levels of the SMN protein,have revolutionised the outlook for patients with an otherwiseincurable, andmostly fatal, condition. However, all three treat-ments come at a significant financial cost For example,Zolgensma (often referred to as “the world’s most expensivedrug”) has a list price of nearly £1.8m per dose. Moreover,a large body of pre-clinical research, supported by emergingdata from patient clinical trials, makes clear that the effective-ness of all current SMA therapies is largely determined byhow early therapy can be delivered.1,2 Thus, pre-symptomatictreatment of patients results in significantly better outcomes -both in terms of patient benefits and financial return on invest-ment - than starting treatment after symptom onset.If pre-symptomatic treatment is a key determinant ofsuccess, then it follows that any possibility to identifySMA patients before the onset of symptoms, and hencebegin treatment as early as possible, should be taken advan-tage of. Importantly, just such an opportunity already exists:newborn screening (NBS) to identify genetic defects under-lying disease. At present, NBS programmes in the UK rou-tinely screen for conditions such as cystic fibrosis andcongenital hypothyroidism, but not SMA. However, NBSfor SMA has already been successfully introduced inmany other countries. For example, SMA is now includedin the Recommended Uniform Screening Panel (RUSP)from the US Department of Health and Human Services.3Likewise, the recent ‘Sun May Arise on SMA’ pilot NBSprogramme in Belgium led to the official adoption of NBSin Southern Belgium in March 2021, with Northern Belgiumincluding SMA in their official program from 2022.4Emerging data from these real-world scenarios confirmthat NBS for SMA is both robust and reliable, whilst alsorepresenting value for money.5Recent approvals from the Scottish Medicines Consortiummean that patients with SMA in Scotland now have access totherapies. Importantly, approval has also been given (at leastfor Zolgensma) for SMA patients in Scotland to receive treat-ment pre-symptomatically. However, while NICE has recom-mended use of Zolgensma for presymptomatic use in SMA,this is under a Managed Access Agreement and thereforenot considered routine care. This lack of approved pre-symptomatic treatment is one reason provided by the UKNational Screening Committee for not approving NBS forSMA at the UK-wide level. However, the availability of pre-symptomatic treatment for SMA in Scotland leads to a situa-tion whereby Scottish SMA patients and their families arebeing denied the possibility of accessing NBS, and potentiallymuch better clinical outcomes, due to decisions being takenand applied at the UK-wide level.NBS does not come without important ethical, societaland financial implications.6 There are myriad reasons whyNBS is not suitable for many genetic conditions atpresent. However, as professionals involved in SMAresearch, diagnosis and patient care in Scotland, webelieve that all of the necessary data, evidence, and thera-peutic approvals are in place to justify the inclusion ofSMA on NBS programmes in Scotland. The inclusion ofNBS for SMA would provide the best possible quality oflife for SMA patients and their families, whilst maximisingthe (not insignificant) return on investment that societymakes in providing access to SMN-restoring therapies.7Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respectto the research, authorship, and/or publication of this article.1Edinburgh Medical School: Biomedical Sciences, The University ofEdinburgh, Edinburgh, UK2NHS Tayside, Dundee, UK3NHS Greater Glasgow and Clyde, Glasgow, UK4NHS Lothian, Edinburgh, UK5University of Aberdeen, Aberdeen, UKCorresponding author:Thomas H. Gillingwater, Edinburgh Medical School: Biomedical Sciences,The University of Edinburgh, Old Medical School (Anatomy), Teviot Place,Edinburgh, EH8 9YL, UK.Email: t.gillingwater@ed.ac.ukLetterScottish Medical Journal1–2© The Author(s) 2022Article reuse guidelines:sagepub.com/journals-permissionsDOI: 10.1177/00369330221078994journals.sagepub.com/home/scmFundingThe author(s) received no financial support for the research,authorship, and/or publication of this article.Declaration of InterestsTHG has served on SMA global advisory boards for Roche. IH hasserved on SMA global advisory boards for Roche, Novartis andBiogen. KM has served on SMA advisory boards for Roche andNovartis.ORCID iDThomas H. Gillingwater https://orcid.org/0000-0002-0306-5577References1. Chaytow H, Faller KME, Huang YT, et al. Spinal muscularatrophy: from approved therapies to future therapeutic targetsfor personalized medicine. Cell Rep Med 2021; 2: 100346.2. De Vivo DC, Bertini E, Swoboda KJ, et al. Nusinersen initiatedin infants during the presymptomatic stage of spinal muscularatrophy: interim efficacy and safety results from the phase 2NURTURE study. Neuromuscul Disord 2019; 29: 842–856.3. Kay DM, Stevens CF, Parker A, et al. Implementation ofpopulation-based newborn screening reveals low incidence ofspinal muscular atrophy. Genet Med 2020; 22: 1296–1302.4. Boemer F, Caberg JH, Beckers P, et al. Three years pilot ofspinal muscular atrophy newborn screening turned into officialprogram in southern Belgium. Sci Rep 2021; 11: 19922.5. Gillingwater TH. Maximising returns: combining newbornscreening with gene therapy for spinal muscular atrophy.J Neurol Neurosurg Psychiatry 2021; 92: 1252.6. Esquerda M, Palau F, Lorenzo D, et al. Ethical questions concern-ing newborn genetic screening. Clin Genet 2021; 99: 93–98.7. European Alliance for Newborn Screening in SMA. Whitepaper -Spinal muscular atrophy: screen at birth, save lives (version 1, 26March 2021). https://www.sma-screening-alliance.org/tools/Accessed 17 November 2021. 2021.2 Scottish Medical Journal 0(0)

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A call to introduce newborn screening for spinal muscular atrophy (SMA) in Scotland

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