Adeno-associated viral vector serotype 9 containing the human SMN gene (AVXS-101) Medicine 12 June 2018 Extended indication Treatment of paediatric patients diagnosed with spinal muscular atrophy Type 1. Therapeutic value No judgement Total cost Registration phase Clinical trials Product Active substance Adeno-associated viral vector serotype 9 containing the human SMN gene (AVXS-101) Domain Neurological disorders Reason of inclusion Main indication Muscular diseases Extended indication Treatment of paediatric patients diagnosed with spinal muscular atrophy Type 1. Current proprietary name Already available biosimilars / generics Proprietary name Manufacturer AveXis Portfolio holder Mechanism of action Unknown Route of administration Intravenous Therapeutical formulation Intravenous drip Budgetting framework Intermural (MSZ) Centre of expertise Additional remarks Non-replicating recombinant AAV9 containing the complimentary deoxyribonucleic acid (cDNA) of the human SMN gene under the control of the cytomegalovirus (CMV) enhancer/chicken-β-actin-hybrid promoter (CB). The AAV inverted terminal repeat (ITR) has been modified to promote intramolecular annealing of the transgene, thus forming a double-stranded transgene ready for transcription. Registration Registration route Centralised (EMA) Type of trajectory Accelerated assessment Particularity New medicine with Priority Medicines (PRIME) ATMP Unknown Submission date 2020 Expected Registration 2020 Orphan drug Yes Registration phase Clinical trials Reimbursement Medicine sluice Additional remarks PRIME granted. AveXis: "AVXS-101, has been granted Orphan Drug Designation for the treatment of all types of spinal muscular atrophy (SMA) and Breakthrough Therapy Designation, as well as Fast Track Designation, for the treatment of SMA Type 1—one of the most life-threatening neurological genetic disorders." Therapeutic value Current treatment options Nusinersen (sluis-product). Therapeutic value No judgement This assessment does not indicate any potential inclusion in the package. Substantiation Ondanks de hele gunstige effecten van dit medicijn op het bewegen en de motoriek, zijn op dit moment de lange termijn effecten en de duurzaamheid van het effect nog niet bekend. Duration of treatment Frequency of administration Dosage per administration References NCT03306277; smaonderzoek.nl/2017/11/09/resultaten-avxs-101-fase-1/ Additional remarks Eenmalige toediening Expected patient volume per year Patient volume 32 - 104 Market share is generally not included unless otherwise stated. Maximum patient volume for sluice References Vergaderstuk Adviescommissie Pakket 26 januari 2018, beoordeling nusinersen (Spinraza®) bij de behandeling van SMA. Additional remarks In de budget impact analyse van nusinersen wordt het volume van patiënten met SMA type 1 bij therapeutische meerwaarde voor 2020 ingeschat op 32. Bij bredere indicatiestelling die alle SMA types omvat kan dit aantal oplopen tot 104. Expected cost per patient per year Cost References Additional remarks Het enige geneesmiddel voor SMA type 1 betreft nusinersen, dit wordt echter nog niet vergoed vanuit het basispakket (sluis). De kosten van dit middel worden geschat tussen de €210.000-270.000 p.p.p.j.. De verwachting is dat AVXS-101 duurder zal zijn gezien dit gaat om een gentherapie met eenmalige toediening. Potential total cost per year Total cost Total cost for sluice Additional remarks Off label use Off label use Unknown Indications off label use References Additional remarks Indication extension Indication extensions Yes Indication extensions SMA Type 2 (intrathecal treatment). References AveXis.com (Phase 1 Trial of AVXS-101 in SMA Type 2 (STRONG)) Additional remarks Planned Trials in SMA: Pivotal Trial of AVXS-101 in SMA Type 1 in Europe (STR1VE EU), Pre-Symptomatic SMA Types 1, 2, 3 (SPRINT), Pediatric “All Comers” with SMA Types 1, 2, 3 (REACH). Other information Additional remarks