Page last updated: 2024-10-15

nusinersen

Description

nusinersen: an antisense oligonucleotide that induces SMN protein expression [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID131801471
MeSH IDM000597138

Synonyms (13)

Synonym
nusinersen
isis 396443
isis-smnrx
1258984-36-9
spinraza
aso-10-27
nusinersen [usan:inn]
5z9sp3x666 ,
rna, (2'-0-(2-methoxyethyi))(p-thio)(m5u-c-a-c-m5u-m5u-m5u-c-a-m5ua- a-m5 u-g-c-m5u-g-g)
unii-5z9sp3x666
isis smnrx
isis-smn(rx)
aso-10-27 ; ionis-smnrx ; isis 396443

Research Excerpts

Overview

Nusinersen is an effective treatment, with gains in motor function occurring particularly in children and SMA type 1, but also in type 2 and 3. The drug specifically binds to the repressor within SMN2 exon 7 to enhance exon7 inclusion and augment production of functional SMN protein.

ExcerptReference
"Nusinersen is a drug used to treat people of all ages who have spinal muscular atrophy. "( Restoration of Nusinersen Levels Following Treatment Interruption in People With Spinal Muscular Atrophy: Simulations Based on a Population Pharmacokinetic Model.
Berger, Z; Farrar, MA; Finkel, RS; Iannaccone, ST; Kirschner, J; Kuntz, NL; MacCannell, D; Mercuri, E; Muntoni, F; Valente, M, 2022
)
"Nusinersen is an effective treatment, with gains in motor function occurring particularly in children and SMA type 1, but also in type 2 and 3, adolescents and adults."( Evaluation of real-life outcome data of patients with spinal muscular atrophy treated with nusinersen in Switzerland.
Baumann, D; Enzmann, C; Hasselmann, O; Jacquier, D; Jung, HH; Klein, A; Kruijshaar, ME; Kuehni, CE; Neuwirth, C; Rüsch, CT; Stettner, GM; Tscherter, A, 2022
)
"Nusinersen is an antisense oligonucleotide, approved by the FDA, which specifically binds to the repressor within SMN2 exon 7 to enhance exon 7 inclusion and augment production of functional SMN protein."( Nusinersen as a Therapeutic Agent for Spinal Muscular Atrophy.
Li, Q, 2020
)
"Nusinersen is a drug approved in December 2016 for treatment of spinal muscular atrophy (SMA). "( Nusinersen injections in adults and children with spinal muscular atrophy: a single-center experience.
Karachunski, P; Nascene, DR; Özütemiz, C, 2020
)
"Nusinersen is an antisense oligonucleotide enhancing the production of the SMN protein."( Efficacy of nusinersen in type 1, 2 and 3 spinal muscular atrophy: Real world data from Hungarian patients.
Andor, I; Czövek, D; Fogarasi, A; Gergely, A; Goschler, Á; Grosz, Z; Herczegfalvi, Á; Jakus, R; Medveczky, E; Molnár, MJ; Schulcz, O; Szabó, L, 2020
)
"Nusinersen is a therapeutic agent for SMA that should be administered intrathecally."( Use of three-dimensional printing of a lumbar skeletal model for intrathecal administration of nusinersen: a brief technical report.
Abe, H; Azuma, K; Hozumi, J; Ino, K; Inoue, R; Konishi, M; Sumitani, M; Tsuchida, R, 2020
)
"Nusinersen is an antisense oligonucleotide that showed dramatic benefits with achievement of motor milestones in infants and improved gross motor function in children."( Delivery of Nusinersen Through an Ommaya Reservoir in Spinal Muscular Atrophy.
Castro, D; Iannaccone, ST; Paul, D; Swift, D; Weprin, B, 2021
)
"Nusinersen is an antisense oligonucleotide drug that was developed for treatment of spinal muscular atrophy (SMA). "( Clinical Outcome of Adult Spinal Muscular Atrophy Patients Treated with Nusinersen: A Case Series Review.
Lam, K; Wu, A, 2020
)
"Nusinersen is an antisense oligonucleotide that increases SMN protein level and is administrated by frequent intrathecal lumbar injections."( Managing intrathecal administration of nusinersen in adolescents and adults with 5q-spinal muscular atrophy and previous spinal surgery.
Fernandes, HDS; Grossklauss, LF; Matsui Júnior, C; Mendonça, RH; Pinto, RBS; Polido, GJ; Reed, UC; Silva, AMSD; Zanoteli, E, 2021
)
"Nusinersen is an antisense oligonucleotide approved for the treatment of spinal muscular atrophy. "( Population pharmacokinetics-based recommendations for a single delayed or missed dose of nusinersen.
Berger, Z; East, L; Farrar, MA; Farwell, W; Finkel, RS; Kirschner, J; MacCannell, D; Mercuri, E; Muntoni, F; Nestorov, I; Peng, J; Zhou, J, 2021
)
"Nusinersen is an intrathecally administered antisense oligonucleotide (ASO) that improves motor function in patients with spinal muscular atrophy (SMA). "( Nusinersen treatment in adult patients with spinal muscular atrophy: a safety analysis of laboratory parameters.
Bolz, S; Deuschl, C; Hagenacker, T; Kizina, K; Kleinschnitz, C; Nonnemacher, M; Stolte, B; Thimm, A; Totzeck, A; Wagner, B, 2021
)
"Nusinersen is an intrathecal antisense oligonucleotide that alters SMN2 pre-mRNA, onasemnogene abeparvovec-xioi is an intravenous SMN1 gene replacement therapy, and risdiplam is an oral small molecule splicing modifier of SMN2."( Selecting disease-modifying medications in 5q spinal muscular atrophy.
Cartwright, MS; Upadhya, S, 2021
)
"Nusinersen is an antisense oligonucleotide that targets intronic splicing silencer N1 (ISS-N1) discovered in 2004 at the University of Massachusetts Medical School."( How the discovery of ISS-N1 led to the first medical therapy for spinal muscular atrophy.
Androphy, EJ; Howell, MD; Singh, NN; Singh, RN, 2017
)
"Nusinersen is a steric block ASO that binds the SMN2 messenger RNA and promotes exon 7 inclusion and thus increases full length SMN expression."( Spinal muscular atrophy: antisense oligonucleotide therapy opens the door to an integrated therapeutic landscape.
Bowerman, M; Talbot, K; Wood, MJA, 2017
)
"Nusinersen is an antisense oligonucleotide drug that modifies pre-messenger RNA splicing of the SMN2 gene and thus promotes increased production of full-length SMN protein."( Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy.
Bennett, CF; Bishop, K; Chiriboga, CA; Connolly, AM; Darras, BT; De Vivo, DC; Farwell, W; Finkel, RS; Gheuens, S; Glanzman, AM; Kirschner, J; Kuntz, NL; Mercuri, E; Montes, J; Saito, K; Schneider, E; Servais, L; Tizzano, E; Topaloglu, H; Tulinius, M; Zhong, ZJ, 2017
)
"Nusinersen is an antisense oligonucleotide drug that modulates pre-messenger RNA splicing of the survival motor neuron 2 ( SMN2) gene. "( Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy.
Bennett, CF; Bishop, KM; Campbell, C; Chiriboga, CA; Connolly, AM; Darras, BT; Day, JW; De Vivo, DC; Farwell, W; Finkel, RS; Foster, R; Gheuens, S; Iannaccone, ST; Kirschner, J; Kuntz, NL; Mazzone, ES; Mercuri, E; Montes, J; Saito, K; Schneider, E; Shieh, PB; Tulinius, M; Yang, Q, 2018
)
"Nusinersen acts as a splicing modifier and has recently been approved for intrathecal treatment of SMA."( Evaluation of Children with SMA Type 1 Under Treatment with Nusinersen within the Expanded Access Program in Germany.
Denecke, J; Giese, K; Hahn, A; Johannsen, J; Kirschner, J; Kölbel, H; Langer, T; Pechmann, A; Schara, U; Schorling, D; Schwartz, O; Stein, S; Theophil, M; Vogt, S; Weiß, C, 2018
)
"Nusinersen is a new treatment for spinal muscular atrophy."( Cost Effectiveness of Nusinersen in the Treatment of Patients with Infantile-Onset and Later-Onset Spinal Muscular Atrophy in Sweden.
Ekelund, M; Forsmark, A; Knight, C; Lloyd, A; Lundqvist, T; Teynor, M; Thompson, R; Vickers, AD; Zuluaga-Sanchez, S, 2019
)
"Nusinersen is a 2'-O-methoxyethyl phosphorothioate-modified antisense drug being developed to treat spinal muscular atrophy. "( Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study.
Bennett, CF; Bishop, KM; Chiriboga, CA; Day, JW; De Vivo, DC; Finkel, RS; Hung, G; Montes, J; Norris, DA; Rigo, F; Schneider, E; Vajsar, J; Xia, S; Yamashita, M, 2016
)
"Nusinersen (SPINRAZA™) is a modified antisense oligonucleotide that binds to a specific sequence in the intron, downstream of exon 7 on the pre-messenger ribonucleic acid (pre-mRNA) of the SMN2 gene."( Nusinersen: First Global Approval.
Hoy, SM, 2017
)

Effects

Nusinersen has been shown to be associated with a significant motor improvement and an increase of the event-free survival. The drug has been covered by public healthcare in France since May 2017.

ExcerptReference
"Nusinersen has been shown to be associated with a significant motor improvement and an increase of the event-free survival."( Sleep architecture and Nusinersen therapy in children with Spinal Muscular Atrophy type 1.
Bruni, O; Cherchi, C; Chiarini Testa, MB; Cutrera, R; D'Amico, A; Ferri, R; Pavone, M; Verrillo, E, 2023
)
"Nusinersen has been covered by public healthcare in France since May 2017."( Effects of nusinersen after one year of treatment in 123 children with SMA type 1 or 2: a French real-life observational study.
Altuzarra, C; Audic, F; Avice, AL; Barnerias, C; Bernoux, D; Beze-Beyrie, P; Cances, C; Chabrol, B; Chouchane, M; Cuisset, JM; de la Banda, MGG; Desguerre, I; Durigneux, J; Espil-Taris, C; Isapof, A; Lagrue, E; Laugel, V; Pauly, V; Pervillé, A; Quijano-Roy, S; Ramirez-Garcia, P; Richelme, C; Ropars, J; Sabouraud, P; Sarret, C; Testard, H; Trommsdorff, V; Vanhulle, C; Vuillerot, C; Walther-Louvier, U, 2020
)
"Nusinersen has been studied for safety, pharmacokinetics, and efficacy in both open-label and randomized controlled trials."( Nusinersen: A Treatment for Spinal Muscular Atrophy.
Claborn, MK; Gildon, BL; Stevens, DL; Walker, CK, 2019
)

Treatment

Nusinersen is the first treatment for spinal muscular atrophy (SMA) Some patients respond well, while others have limited response. Treatment may be effective and safe, even after placement of a VPS.

ExcerptReference
"Nusinersen-treated SMA1 patients may sustain facial deformities, feeding problems, and severe scoliosis, all of which affect their respiratory system. "( Nonrespiratory complications of nusinersen-treated spinal muscular atrophy type 1 patients.
Amirav, I; Be'er, M; Cahal, M; Fattal-Valevski, A; Lavie, M; Ovadia, D; Rochman, M; Sadot, E; Sagi, L; Yerushalmy Feler, A, 2022
)
"Nusinersen treatment ameliorates the clinical outcome of SMA, however, some patients respond well, while others have limited response."( Response of plasma microRNAs to nusinersen treatment in patients with SMA.
Aragon-Gawinska, K; Doreste, B; Muntoni, F; Ridout, D; Scoto, M; Servais, L; Zaharieva, IT; Zhou, H, 2022
)
"Nusinersen treatment is associated with some improvements in adult SMA patients. "( Nusinersen in adult patients with 5q spinal muscular atrophy: A multicenter observational cohorts' study.
Dominguez, R; Exposito, JM; González, L; Hervás, D; Kapetanovic Garcia, S; Marco, C; Medina Castillo, J; Moreno Escribano, A; Muelas, N; Nascimiento-Osorio, AE; Natera de Benito, D; Ñungo Garzón, NC; Pitarch Castellano, I; Povedano, M; Sevilla, T; Vázquez-Costa, JF, 2022
)
"Nusinersen is the first treatment for spinal muscular atrophy (SMA)."( The reimbursement for expensive medicines: stakeholder perspectives on the SMA medicine nusinersen and the Dutch Coverage Lock policy.
Delden, JJMV; Fadaei, S; Onrust, MR; Scheijmans, FEV; van der Graaf, R; van der Pol, WL; van Thiel, GJMW; Zomers, ML, 2022
)
"Nusinersen-treated patients with SMA types 1 and 2 between 2017 and 2022 were retrospectively reviewed. "( Long-term efficacy of nusinersen and its evaluation in adolescent and adult patients with spinal muscular atrophy types 1 and 2.
Azuma, Y; Ito, T; Iwayama, H; Kawahara, K; Kawajiri, H; Kimura, S; Kumagai, T; Kurahashi, H; Numoto, S; Okumura, A; Takagi, M; Yanase, A; Yasue, Y, 2023
)
"Nusinersen treatment may be effective and safe, even after placement of a VPS. "( Intrathecal nusinersen treatment after ventriculo-peritoneal shunt placement: A case report focusing on the neurofilament light chain in cerebrospinal fluid.
Chiyonobu, T; Kasai, T; Nishio, H; Shiomi, K; Tatebe, H; Tokuda, T; Tozawa, T, 2020
)
"Nusinersen treatment was correlated with higher REE both in spontaneously breathing and mechanically ventilated patients."( Predictive energy equations for spinal muscular atrophy type I children.
Agosto, C; Baranello, G; Bassano, M; Battezzati, A; Bedogni, G; Bertini, E; Bertoli, S; Bruno, C; D'Amico, A; De Amicis, R; Foppiani, A; Giaquinto, E; Leone, A; Masson, R; Mastella, C; Pedemonte, M; Ravella, S, 2020
)
"Nusinersen treatment before symptom onset in children with presymptomatic SMA produced near-normal motor development."( Nusinersen treatment of spinal muscular atrophy - a systematic review.
Albrechtsen, SS; Boesen, MS; Born, AP, 2020
)
"Nusinersen, the only treatment approved by the United States Food and Drug Administration for spinal muscular atrophy (SMA), is delivered intrathecally. "( Transforaminal intrathecal delivery of nusinersen using cone-beam computed tomography for children with spinal muscular atrophy and extensive surgical instrumentation: early results of technical success and safety.
Apkon, SD; Koo, KSH; Monroe, EJ; Natarajan, N; Shaw, DWW; Shivaram, GM; Weaver, JJ, 2018
)
"Nusinersen treatment prolongs survival of patients with type 1 SMA and allows motor milestone acquisition."( Nusinersen treatment of spinal muscular atrophy: current knowledge and existing gaps.
Gidaro, T; Servais, L, 2019
)
"Nusinersen is a new treatment for spinal muscular atrophy."( Cost Effectiveness of Nusinersen in the Treatment of Patients with Infantile-Onset and Later-Onset Spinal Muscular Atrophy in Sweden.
Ekelund, M; Forsmark, A; Knight, C; Lloyd, A; Lundqvist, T; Teynor, M; Thompson, R; Vickers, AD; Zuluaga-Sanchez, S, 2019
)
"Nusinersen treatment over ∼3 years resulted in motor function improvements and disease activity stabilization not observed in natural history cohorts. "( Nusinersen in later-onset spinal muscular atrophy: Long-term results from the phase 1/2 studies.
Bennett, CF; Bhan, I; Bishop, KM; Chiriboga, CA; Darras, BT; De Vivo, DC; Farwell, W; Gheuens, S; Green, AM; Iannaccone, ST; Mignon, L; Montes, J; Schneider, E; Shefner, JM; Sun, P; Swoboda, KJ; Xia, S, 2019
)
"Treatment with nusinersen has demonstrated significant and clinically meaningful benefits in clinical trials in infants and children with spinal muscular atrophy (SMA)."( An Integrated Safety Analysis of Infants and Children with Symptomatic Spinal Muscular Atrophy (SMA) Treated with Nusinersen in Seven Clinical Trials.
Bhan, I; Darras, BT; Farrar, MA; Farwell, W; Finkel, RS; Foster, R; Gheuens, S; Hughes, SG; Mercuri, E, 2019
)
"Treatment with nusinersen was initiated when she was 7 years old."( Intrathecal nusinersen treatment after ventriculo-peritoneal shunt placement: A case report focusing on the neurofilament light chain in cerebrospinal fluid.
Chiyonobu, T; Kasai, T; Nishio, H; Shiomi, K; Tatebe, H; Tokuda, T; Tozawa, T, 2020
)
"Treatment with Nusinersen in SMA3 improves motor function in longstanding disease even in clinically advanced stages; however, after discontinuation of treatment, further progression mirroring the natural history of the disease is anticipated."( Effect of Discontinuation of Nusinersen Treatment in Long-Standing SMA3.
Abicht, A; Hiebeler, M; Reilich, P; Walter, MC, 2021
)
"Treatment with Nusinersen was initiated in 20 children aged from 2 to 50 months. "( Single-center experience with intrathecal administration of Nusinersen in children with spinal muscular atrophy type 1.
Kirschner, J; Langer, T; Pechmann, A; Wider, S, 2018
)
"Treatment with nusinersen resulted in overall survival and quality-adjusted life-year benefits but with incremental costs above 21 million SEK (€2 million) [mainly associated with maintenance treatment with nusinersen over a patient's lifespan]. "( Cost Effectiveness of Nusinersen in the Treatment of Patients with Infantile-Onset and Later-Onset Spinal Muscular Atrophy in Sweden.
Ekelund, M; Forsmark, A; Knight, C; Lloyd, A; Lundqvist, T; Teynor, M; Thompson, R; Vickers, AD; Zuluaga-Sanchez, S, 2019
)

Toxicity

Intrathecal nusinersen is generally safe and well-tolerated. Patients with spinal muscular atrophy (SMA) who might benefit from intrathecal antisense oligonucleotide therapy have scoliosis or spinal fusion that precludes safe drug delivery.

ExcerptReference
"Many patients with spinal muscular atrophy (SMA) who might benefit from intrathecal antisense oligonucleotide (nusinersen) therapy have scoliosis or spinal fusion that precludes safe drug delivery."( Preliminary Safety and Tolerability of a Novel Subcutaneous Intrathecal Catheter System for Repeated Outpatient Dosing of Nusinersen to Children and Adults With Spinal Muscular Atrophy.
Brigatti, KW; Carson, VJ; Fox, MD; Hendrickson, C; Mackenzie, W; Miller, F; Puffenberger, EG; Reed, RM; Robinson, DL; Strauss, KA; Young, M,
)
"Preliminary observations reveal the SIC to be relatively safe and well tolerated in SMA patients with advanced disease and spinal fusion."( Preliminary Safety and Tolerability of a Novel Subcutaneous Intrathecal Catheter System for Repeated Outpatient Dosing of Nusinersen to Children and Adults With Spinal Muscular Atrophy.
Brigatti, KW; Carson, VJ; Fox, MD; Hendrickson, C; Mackenzie, W; Miller, F; Puffenberger, EG; Reed, RM; Robinson, DL; Strauss, KA; Young, M,
)
" Safety assessments included incidence of adverse events (AEs), physical and neurological examinations, vital signs, clinical laboratory tests (serum chemistry, hematology, and urinalysis), and electrocardiograms."( An Integrated Safety Analysis of Infants and Children with Symptomatic Spinal Muscular Atrophy (SMA) Treated with Nusinersen in Seven Clinical Trials.
Bhan, I; Darras, BT; Farrar, MA; Farwell, W; Finkel, RS; Foster, R; Gheuens, S; Hughes, SG; Mercuri, E, 2019
)
" Eleven patients reported adverse events that were related to the study procedures, comprising back pain in seven patients and post-lumbar-puncture headache following intrathecal administration in four patients."( Safety and Treatment Effects of Nusinersen in Longstanding Adult 5q-SMA Type 3 - A Prospective Observational Study.
Greckl, E; Hiebeler, M; Kirschner, J; Lochmüller, H; Pechmann, A; Schoser, B; Stahl, K; Stauber, J; Thiele, S; Walter, MC; Wenninger, S, 2019
)
" Eight infants had adverse events considered possibly related to nusinersen by the study investigators."( Nusinersen initiated in infants during the presymptomatic stage of spinal muscular atrophy: Interim efficacy and safety results from the Phase 2 NURTURE study.
Ben-Omran, T; Bertini, E; Bhan, I; Braley, G; Butterfield, RJ; Crawford, TO; De Vivo, DC; Farwell, W; Finkel, RS; Foster, R; Fradette, S; Gheuens, S; Hwu, WL; Johnson, K; Jong, YJ; Kerr, D; Kirschner, J; Kuntz, NL; Parsons, JA; Petrillo, M; Reyna, SP; Ryan, MM; Sandrock, AW; Sansone, VA; Shu, F; Staropoli, JF; Stebbins, C; Swoboda, KJ; Topaloglu, H, 2019
)
" The study's outcome measures were technical success, adverse events and radiation exposure."( Computed-tomography-guided transforaminal intrathecal nusinersen injection in adults with spinal muscular atrophy type 2 and severe spinal deformity. Feasibility, safety and radiation exposure considerations.
Brountzos, E; Efstathopoulos, E; Filippiadis, D; Palaiodimou, L; Palialexis, K; Papadopoulou, M; Ploussi, A; Reppas, L; Spiliopoulos, S; Tsivgoulis, G; Zompola, C, 2020
)
" No adverse events were documented following the procedures."( Computed-tomography-guided transforaminal intrathecal nusinersen injection in adults with spinal muscular atrophy type 2 and severe spinal deformity. Feasibility, safety and radiation exposure considerations.
Brountzos, E; Efstathopoulos, E; Filippiadis, D; Palaiodimou, L; Palialexis, K; Papadopoulou, M; Ploussi, A; Reppas, L; Spiliopoulos, S; Tsivgoulis, G; Zompola, C, 2020
)
" There were no nusinersen-related adverse events (AEs) and no study discontinuations due to nusinersen-related AEs."( Safety and efficacy of nusinersen in spinal muscular atrophy: The EMBRACE study.
Acsadi, G; Castro, D; Crawford, TO; Farwell, W; Gambino, G; Müller-Felber, W; Natarajan, N; Ramirez-Schrempp, D; Richardson, R; Shieh, PB; Sun, P, 2021
)
" One treatment-related serious adverse event (emesis leading to intubation) occurred during general anesthesia."( Laboratory monitoring of nusinersen safety.
Connolly, AM; Gibbons, JL; Goedeker, NL; Varadhachary, AS; Zaidman, CM, 2021
)
"Intrathecal nusinersen is generally safe and well-tolerated, including in patients requiring oral anxiolysis, general sedation, and fluoroscopic guidance."( Laboratory monitoring of nusinersen safety.
Connolly, AM; Gibbons, JL; Goedeker, NL; Varadhachary, AS; Zaidman, CM, 2021
)
" Biogen safety database data up to June 30, 2019 were also included to capture adverse events (AEs) from after the interim analysis cutoff date."( Real-world safety of nusinersen in Japan: results from an interim analysis of a post-marketing surveillance and safety database.
Hoshino, M; Makioka, H; Matsuda, N; Nakamura, G; Takasaki, S; Wataya, T, 2023
)
" The only side effect was post lumbar puncture headache."( Longer-term follow-up of nusinersen efficacy and safety in adult patients with spinal muscular atrophy types 2 and 3.
Abraham, A; Abramovich, B; Ben-Shushan, S; Drory, VE; Fainmesser, Y; Lavon, A; Spector, L, 2022
)
" Except for 2 fatal cases, not related to the treatment, no serious adverse events were reported."( Safety, tolerability, and efficacy of a widely available nusinersen program for Polish children with Spinal Muscular Atrophy.
Biedroń, A; Boćkowski, L; Chmielewski, D; Cichosz, D; Czyżyk, E; Dudzińska, M; Gadowska, E; Jasiński, M; Kempisty, A; Kostera-Pruszczyk, A; Kotulska, K; Masztalerz, A; Mazurkiewicz-Bełdzińska, M; Młynarczyk, E; Pierzchlewicz, K; Pietruszewski, J; Przysło, Ł; Rabczenko, D; Steinborn, B; Tomaszek, K, 2022
)
"The FDA Adverse Event Reporting System database was used to analyze drug safety, and a case (SMA drug)/noncase (all other drugs in the database) approach was employed to estimate safety signals through disproportionality analysis and reporting odds ratio (ROR)."( Safety Concerns with Nusinersen, Risdiplam, and Onasemnogene Abeparvovec in Spinal Muscular Atrophy: A Real-World Pharmacovigilance Study.
Chen, Z; Guan, S; Lin, W; Lu, M; Wang, M; Wang, X; Wu, Y; Zhuang, W, 2023
)

Pharmacokinetics

A pharmacokinetic (PK) model was developed for nusinersen, an antisense oligonucleotide (ASO) That is the first approved treatment for spinal muscular atrophy (SMA)

ExcerptReference
"A pharmacokinetic (PK) model was developed for nusinersen, an antisense oligonucleotide (ASO) that is the first approved treatment for spinal muscular atrophy (SMA)."( A Semi-Mechanistic Population Pharmacokinetic Model of Nusinersen: An Antisense Oligonucleotide for the Treatment of Spinal Muscular Atrophy.
Biliouris, K; Fey, R; Gaitonde, P; Henry, S; Lesko, LJ; Nestorov, I; Norris, DA; Rogge, M; Schmidt, S; Trame, MN; Wang, Y; Yin, W, 2018
)
" This population pharmacokinetic model was developed to clarify how to maintain targeted nusinersen exposure after an unforeseen one-time delay or missed dose."( Population pharmacokinetics-based recommendations for a single delayed or missed dose of nusinersen.
Berger, Z; East, L; Farrar, MA; Farwell, W; Finkel, RS; Kirschner, J; MacCannell, D; Mercuri, E; Muntoni, F; Nestorov, I; Peng, J; Zhou, J, 2021
)
"Population pharmacokinetic models using integrated pharmacokinetic data from ten nusinersen clinical trials that included a broad range of participants with spinal muscular atrophy treated with intrathecal nusinersen were used to investigate different durations of treatment interruptions during maintenance treatment."( Restoration of Nusinersen Levels Following Treatment Interruption in People With Spinal Muscular Atrophy: Simulations Based on a Population Pharmacokinetic Model.
Berger, Z; Farrar, MA; Finkel, RS; Iannaccone, ST; Kirschner, J; Kuntz, NL; MacCannell, D; Mercuri, E; Muntoni, F; Valente, M, 2022
)
"Our pharmacokinetic modeling indicates the following regimen will lead to optimal restoration of nusinersen CSF levels after treatment interruption: two doses of nusinersen should be administered at 14-day intervals following treatment interruptions of ≥ 8 to < 16 months since the last dose, and three doses of nusinersen at 14-day intervals for treatment interruptions of ≥ 16 to < 40 months since the last maintenance dose, with subsequent maintenance dosing every 4 months in both instances."( Restoration of Nusinersen Levels Following Treatment Interruption in People With Spinal Muscular Atrophy: Simulations Based on a Population Pharmacokinetic Model.
Berger, Z; Farrar, MA; Finkel, RS; Iannaccone, ST; Kirschner, J; Kuntz, NL; MacCannell, D; Mercuri, E; Muntoni, F; Valente, M, 2022
)

Dosage Studied

The most common approved dosing regimen is four intrathecal loading doses of nusinersen 12 mg. The first three are administered at 14-day intervals followed by a fourth dose 30 days later, and then 12-mg maintenance doses are administered every 4 months thereafter. Some people may miss dose(s) or may stop nusineren treatment at some point during maintenance dosing.

ExcerptReference
" In addition to the benefit to spinal muscular atrophy patients, there are discoveries from nusinersen that can be applied to other neurological diseases, including method of delivery, doses, tolerability of intrathecally delivered antisense drugs, and the biodistribution of intrathecal dosed antisense drugs."( Antisense Oligonucleotide Therapies for Neurodegenerative Diseases.
Bennett, CF; Cleveland, DW; Krainer, AR, 2019
)
" Treatment of SMA with nusinersen is based on a fixed dosing regimen."( Neurofilament Heavy Chain and Tau Protein Are Not Elevated in Cerebrospinal Fluid of Adult Patients with Spinal Muscular Atrophy during Loading with Nusinersen.
Bolz, S; Hagenacker, T; Kizina, K; Kleinschnitz, C; Schlag, M; Stolte, B; Thimm, A; Totzeck, A, 2019
)
"Onasemnogene abeparvovec was recently approved for the treatment of spinal muscular atrophy (SMA) in children younger than two years; however, clinical trials were primarily completed in children younger than seven months, so practical experience dosing older children began in summer 2019."( Clinical Experience With Gene Therapy in Older Patients With Spinal Muscular Atrophy.
Battista, V; Flickinger, J; Jones, JN; Kichula, EA; Matesanz, SE, 2021
)
" Simulations demonstrated that the impact of a one-time delay in dosing or a missed dose on median cerebrospinal fluid exposures depended on duration of interruption and the regimen phase in which it occurred."( Population pharmacokinetics-based recommendations for a single delayed or missed dose of nusinersen.
Berger, Z; East, L; Farrar, MA; Farwell, W; Finkel, RS; Kirschner, J; MacCannell, D; Mercuri, E; Muntoni, F; Nestorov, I; Peng, J; Zhou, J, 2021
)
" The implanted port permits dosing in an outpatient setting and avoids the need for multiple future radiologic procedures, and it reduces discomfort, procedural costs and potential risks and sequelae of multiple anesthetics and radiation exposures."( Intrathecal catheter and port placement for nusinersen infusion in children with spinal muscular atrophy and spinal fusion.
Berde, CB; Padua, HM; Shashi, KK; Stone, SSD, 2021
)
" Collected data included medical history, dosage and administration, and AEs."( Real-world safety of nusinersen in Japan: results from an interim analysis of a post-marketing surveillance and safety database.
Hoshino, M; Makioka, H; Matsuda, N; Nakamura, G; Takasaki, S; Wataya, T, 2023
)
" The most common approved dosing regimen is four intrathecal loading doses of nusinersen 12 mg; the first three are administered at 14-day intervals followed by a fourth dose 30 days later, and then 12-mg maintenance doses are administered every 4 months thereafter."( Restoration of Nusinersen Levels Following Treatment Interruption in People With Spinal Muscular Atrophy: Simulations Based on a Population Pharmacokinetic Model.
Berger, Z; Farrar, MA; Finkel, RS; Iannaccone, ST; Kirschner, J; Kuntz, NL; MacCannell, D; Mercuri, E; Muntoni, F; Valente, M, 2022
)
"The objective of this report is to describe dosing regimens that allow for the most rapid restoration of steady-state concentrations of nusinersen in the cerebrospinal fluid (CSF) following a treatment interruption during maintenance dosing."( Restoration of Nusinersen Levels Following Treatment Interruption in People With Spinal Muscular Atrophy: Simulations Based on a Population Pharmacokinetic Model.
Berger, Z; Farrar, MA; Finkel, RS; Iannaccone, ST; Kirschner, J; Kuntz, NL; MacCannell, D; Mercuri, E; Muntoni, F; Valente, M, 2022
)
" Potential dosing regimens for re-initiation of nusinersen were evaluated, with the goal of achieving the quickest restoration of steady-state nusinersen CSF concentrations without exceeding maximal CSF exposures observed during the initial loading period."( Restoration of Nusinersen Levels Following Treatment Interruption in People With Spinal Muscular Atrophy: Simulations Based on a Population Pharmacokinetic Model.
Berger, Z; Farrar, MA; Finkel, RS; Iannaccone, ST; Kirschner, J; Kuntz, NL; MacCannell, D; Mercuri, E; Muntoni, F; Valente, M, 2022
)
"Our pharmacokinetic modeling indicates the following regimen will lead to optimal restoration of nusinersen CSF levels after treatment interruption: two doses of nusinersen should be administered at 14-day intervals following treatment interruptions of ≥ 8 to < 16 months since the last dose, and three doses of nusinersen at 14-day intervals for treatment interruptions of ≥ 16 to < 40 months since the last maintenance dose, with subsequent maintenance dosing every 4 months in both instances."( Restoration of Nusinersen Levels Following Treatment Interruption in People With Spinal Muscular Atrophy: Simulations Based on a Population Pharmacokinetic Model.
Berger, Z; Farrar, MA; Finkel, RS; Iannaccone, ST; Kirschner, J; Kuntz, NL; MacCannell, D; Mercuri, E; Muntoni, F; Valente, M, 2022
)
" Some people may miss dose(s) or may stop nusinersen treatment at some point during maintenance dosing and then may want to continue treatment."( Restoration of Nusinersen Levels Following Treatment Interruption in People With Spinal Muscular Atrophy: Simulations Based on a Population Pharmacokinetic Model.
Berger, Z; Farrar, MA; Finkel, RS; Iannaccone, ST; Kirschner, J; Kuntz, NL; MacCannell, D; Mercuri, E; Muntoni, F; Valente, M, 2022
)
" The patients were already in the maintenance phase of the dosing protocol and were prospectively evaluated for US-guided transforaminal approach."( Ultrasound-guided transforaminal approach for nusinersen delivery in adult spinal muscle atrophy patients with challenging access.
Salapura, V; Snoj, Ž, 2022
)
" Most patients followed the dosing schedule across the loading and maintenance dose periods."( Real-world Adherence to Nusinersen in Adults with Spinal Muscular Atrophy in the US: A Multi-site Chart Review Study.
Ajroud-Driss, S; Cartwright, MS; Chandak, A; Choi, JM; Elman, L; Frey, MR; Heiman-Patterson, T; Khachatryan, A; Martinez, M; McCormick, ME; Michelson, D; Paradis, AD; Proud, CM; Youn, B, 2022
)
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (362)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's0 (0.00)29.6817
2010's129 (35.64)24.3611
2020's233 (64.36)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials14 (3.84%)5.53%
Reviews54 (14.79%)6.00%
Case Studies31 (8.49%)4.05%
Observational22 (6.03%)0.25%
Other244 (66.85%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]