Open main menu

Wikipedia β

Nusinersen (INN),[1] marketed as Spinraza,[3] is a drug used in treating spinal muscular atrophy (SMA),[4] a rare neuromuscular disorder. In December 2016, it became the first approved drug used in treating this disorder.

Nusinersen sodium colored.svg
Clinical data
Trade names Spinraza
ATC code
  • None
Legal status
Legal status
Pharmacokinetic data
Metabolism Exonuclease (3’- and 5’)-mediated hydrolysis
Biological half-life 135–177 days (in CSF), 63–87 days (in plasma)
CAS Number
Chemical and physical data
Formula C234H323N61Na17O128P17S17[2]
Molar mass 7501 Da[2]


Medical useEdit

The drug is used to treat spinal muscular atrophy associated with a mutation in the SMN1 gene. It is administered directly to the central nervous system (CNS) using intrathecal injection.[2]

In clinical trials, the drug halted the disease progression. In around 60% of infants affected by type 1 spinal muscular atrophy, the drug also significantly improved motor function.[2]

Side effectsEdit

Like other antisense drugs, there is a risk of abnormalities in blood clotting and a reduction in platelets as well as a risk of kidney damage.[2]

In clinical trials, people treated with nusinersen had an increased risk of upper and lower respiratory infections and congestion, ear infections, constipation, pulmonary aspiration, teething, and scoliosis. One infant in a clinical trial had severe lowering of salt levels and several had rashes. There is a risk that growth of infants and children might be stunted. In older clinical trial subjects, the most common adverse events were headache, back pain, and adverse effects from the spinal injection.[2]

Some people may develop antibodies against the drug; as of December 2016 it was unclear what effect this might have on efficacy or safety.[2]


Spinal muscular atrophy is caused by loss-of-function mutations in the SMN1 gene which codes for survival motor neuron (SMN) protein. Patients survive owing to low amounts of the SMN protein produced from the SMN2 gene. Nusinersen modulates alternate splicing of the SMN2 gene, functionally converting it into SMN1 gene, thus increasing the level of SMN protein in the CNS.[5]

The drug distributes to CNS and to peripheral tissues.[2]

The half-life is estimated to be 135 to 177 days in CSF and 63 to 87 days in blood plasma. The drug is metabolized via exonuclease (3’- and 5’)-mediated hydrolysis and does not interact with CYP450 enzymes.[2] The primary route of elimination is likely by urinary excretion for nusinersen and its metabolites.[2]


Nusinersen is an antisense oligonucleotide in which the 2’-hydroxy groups of the ribofuranosyl rings are replaced with 2’-O-2-methoxyethyl groups and the phosphate linkages are replaced with phosphorothioate linkages.[2][5]


Nusinersen was discovered in a collaboration between Adrian Krainer at Cold Spring Harbor Laboratory and Ionis Pharmaceuticals (formerly called Isis Pharmaceuticals).[6][7][8][9] Partial work was done at University of Massachusetts funded by Cure SMA.[10]

Starting in 2012, Ionis partnered with Biogen on development and in 2015 Biogen acquired an exclusive license to the drug for a US$75 million license fee, milestone payments up to US$150 million, and tiered royalties thereafter; Biogen also paid the costs of development subsequent to taking the license.[11] The license to Biogen included licenses to intellectual property that Ionis had acquired from Cold Spring Harbor Laboratory and University of Massachusetts.[12]

This drug costs 6 million Hong Kong Dollar for one year.[13]

In November 2016, the new drug application was accepted under the FDA's priority review process on the strength of the Phase III trial and the unmet need, and was also accepted for review at the European Medicines Agency (EMA) at that time.[14][15] It was approved by the FDA in December 2016 as the first drug for SMA.[16] Likewise, in April 2017, EMA recommended that nusinersen be approved for marketing in the European Union to treat spinal muscular atrophy.[17] In June 2017, nusinersen was approved for marketing in European Union.[18]

Society and cultureEdit

Nusinersen has orphan drug designation in the United States and the European Union.[19]

According to the New York Times, Spinraza "will be among the most expensive drugs in the world", with an estimated cost US$750,000 in the first year of treatment and "about US$375,000 annually after that."[15] In August 2016 peak annual sales of nusinersen were estimated to reach around $1.7 billion.[20]


  1. ^ a b "International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names: List 74" (PDF). World Health Organization. pp. 413–14. Retrieved 13 March 2017. 
  2. ^ a b c d e f g h i j k "Nusinersen US Label" (PDF). FDA. December 2016.  For updates see FDA index page for NDA 209531
  3. ^ "Nusinersen". AdisInsight. Retrieved 1 January 2017. 
  4. ^ Ottesen, Eric W. (2017-01-01). "ISS-N1 makes the first FDA-approved drug for spinal muscular atrophy". Translational Neuroscience. 8 (1): 1–6. ISSN 2081-6936. PMC 5382937 . PMID 28400976. doi:10.1515/tnsci-2017-0001. 
  5. ^ a b Zanetta, C; Nizzardo, M; Simone, C; Monguzzi, E; Bresolin, N; Comi, GP; Corti, S (1 January 2014). "Molecular Therapeutic Strategies for Spinal Muscular Atrophies: Current and Future Clinical Trials". Clinical Therapeutics. 36 (1): 128–40. PMID 24360800. doi:10.1016/j.clinthera.2013.11.006. 
  6. ^ Garber, K (11 October 2016). "Big win possible for Ionis/Biogen antisense drug in muscular atrophy.". Nature Biotechnology. 34 (10): 1002–1003. PMID 27727217. doi:10.1038/nbt1016-1002. 
  7. ^ Wadman, Meredith (23 December 2016). "Updated: FDA approves drug that rescues babies with fatal neurodegenerative disease". Science. 
  8. ^ Offord, Catherine (December 1, 2016). "Oligonucleotide Therapeutics Near Approval". The Scientist. 
  9. ^ Tarr, Peter (24 December 2016). "CSHL FDA approval of life-saving SMA drug is hailed by its researcher-inventor at CSHL". Cold Spring Harbor Laboratory. 
  10. ^ "Therapeutic Approaches". Cure SMA. Retrieved 1 January 2017. 
  11. ^ "Biogen Shells Out $75M to Develop Ionis' Nusinersen after Positive Phase III Results", Genetic Engineering News, August 1, 2016 
  12. ^ "Press release: Biogen and Ionis Pharmaceuticals Report Nusinersen Meets Primary Endpoint at Interim Analysis of Phase 3 ENDEAR Study in Infantile-Onset Spinal Muscular Atrophy | Biogen Media". Biogen. August 1, 2016. 
  13. ^ "孖仔患罕見病 首年藥費1200萬 每年用藥「賣樓不夠」 母嘆港沒政策支援" (in Chinese). Mingpao Daily. 22 August 2017. Retrieved 22 August 2017. 
  14. ^ "Regulatory Applications for SMA Therapy Nusinersen Accepted in US, EU". BioNews Services, LLC. Retrieved 2016-11-15. 
  15. ^ a b Katie Thomas (December 30, 2016). "Costly Drug for Fatal Muscular Disease Wins F.D.A. Approval". New York Times. 
  16. ^ Grant, Charley (2016-12-27). "Surprise Drug Approval Is Holiday Gift for Biogen". Wall Street Journal. ISSN 0099-9660. Retrieved 2016-12-27. 
  17. ^ "First medicine for spinal muscular atrophy: Orphan medicine Spinraza recommended by CHMP under accelerated assessment" (PDF). European Medicines Agency. 2017-04-21. Retrieved 2017-04-21. 
  18. ^ "SPINRAZA® (Nusinersen) Approved in the European Union as First Treatment for Spinal Muscular Atrophy". AFP. 2017-06-01. Retrieved 2017-06-01. 
  19. ^ "Nusinersen". UK Specialist Pharmacy Service. Retrieved 31 December 2016. 
  20. ^ Lawrence, Stacy (August 1, 2016). "Biogen pays $75M to Ionis on early PhIII antisense results | FierceBiotech". 

Further readingEdit

  • Finkel, Richard S; Chiriboga, Claudia A; Vajsar, Jiri; Day, John W; Montes, Jacqueline; De Vivo, Darryl C; Yamashita, Mason; Rigo, Frank; Hung, Gene; Schneider, Eugene; Norris, Daniel A; Xia, Shuting; Bennett, C Frank; Bishop, Kathie M (2016). "Treatment of infantile-onset spinal muscular atrophy with nusinersen: A phase 2, open-label, dose-escalation study". The Lancet. 388 (10063): 3017. doi:10.1016/S0140-6736(16)31408-8.