Skip to main content

Nusinersen: First Global Approval

Abstract

Spinal muscular atrophy (SMA) is a rare autosomal recessive disorder characterized by muscle atrophy and weakness resulting from motor neuron degeneration in the spinal cord and brainstem. It is most commonly caused by insufficient levels of survival motor neuron (SMN) protein (which is critical for motor neuron maintenance) secondary to deletions or mutations in the SMN1 gene. 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. This modulates the splicing of the SMN2 mRNA transcript to include exon 7, thereby increasing the production of full-length SMN protein. Nusinersen is approved in the USA for intrathecal use in paediatric and adult patients with SMA. Regulatory assessments for nusinersen as a treatment for SMA are underway in the EU and several other countries. This article summarizes the milestones in the development of nusinersen leading to this first approval for SMA in paediatric and adult patients.

This is a preview of subscription content, access via your institution.

References

  1. 1.

    Castro D, Iannaccone ST. Spinal muscular atrophy: therapeutic strategies. Curr Treat Options Neurol. 2014;16(11):316.

    Article  PubMed  Google Scholar 

  2. 2.

    Farrar MA, Park SB, Vucic S, et al. Emerging therapies and challenges in spinal muscular atrophy. Ann Neurol. 2016. doi:10.1002/ana.24864.

  3. 3.

    US National Library of Medicine. Genetics Home Reference: spinal muscular atrophy. 2017. https://ghr.nlm.nih.gov/. Accessed 16 Jan 2017.

  4. 4.

    Lefebvre S, Burglen L, Reboullet S, et al. Identification and characterization of a spinal muscular atrophy-determining gene. Cell. 1995;80(1):155–65.

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Garber K. Big win possible for Ionis/Biogen antisense drug in muscular atrophy. Nat Biotech. 2016;34(10):1002–3.

    CAS  Article  Google Scholar 

  6. 6.

    Biogen Inc. SPINRAZA (nusinersen) injection, for intrathecal use: US prescribing information. 2016. http://www.fda.gov/. Accessed 9 Jan 2017.

  7. 7.

    US Food and Drug Administration. FDA approves first drug for spinal muscular atrophy. 2016. http://www.fda.gov. Accessed 17 Jan 2017.

  8. 8.

    Biogen. US FDA approves Biogen’s SPINRAZA™ (nusinersen), the first treatment for spinal muscular atrophy. 2016. https://www.biogen.com/. Accessed 9 Feb 2017.

  9. 9.

    Biogen. Biogen and Ionis Pharmaceuticals announce SPINRAZA (nusinersen) meets primary endpoint at interim analysis of phase 3 CHERISH study in later-onset spinal muscular atrophy. 2016. http://www.biogen.com/. Accessed 26 Jan 2017.

  10. 10.

    US FDA Center for Drug Evaluation and Research. Medical review(s). 2016. http://www.fda.gov/. Accessed 24 Jan 2017.

  11. 11.

    Finkel RS, Chiriboga CA, Vajsar J, et al. Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study. Lancet. 2017;388(10063):3017–26.

    Article  Google Scholar 

  12. 12.

    US FDA Center for Drug Evaluation and Research. Clinical pharmacology and biopharmaceutics review(s). 2016. http://www.fda.gov/. Accessed 24 Jan 2017.

  13. 13.

    Chiriboga CA, Swoboda KJ, Darras BT, et al. Results from a phase 1 study of nusinersen (ISIS-SMN(Rx)) in children with spinal muscular atrophy. Neurology. 2016;86(10):890–7.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Biogen. Biogen and Ionis Pharmaceuticals report nusinersen meets primary endpoint at interim analysis of phase 3 ENDEAR study in infantile-onset spinal muscular atrophy. 2016. http://www.biogen.com/. Accessed 17 Jan 2017.

  15. 15.

    Biogen. New data presented at World Muscle Society Congress support potential benefit of investigational treatment nusinersen in spinal muscular atrophy. 2016. http://www.biogen.com/. Accessed 26 Jan 2017.

  16. 16.

    Darras B, Chiriboga C, Swoboda K, et al. Results of a phase 2 study of ISIS-SMNRx in children with spinal muscular atrophy [abstract no. G.O.18]. Neuromuscul Disord. 2014;24(9–10):920.

    Article  Google Scholar 

Download references

Disclosure

The preparation of this review was not supported by any external funding. During the peer review process the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from any comments received were made by the author on the basis of scientific completeness and accuracy. Sheridan Hoy is a salaried employee of Adis, Springer SBM.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Sheridan M. Hoy.

Additional information

This profile has been extracted and modified from the AdisInsight database. AdisInsight tracks drug development worldwide through the entire development process, from discovery, through pre-clinical and clinical studies to market launch and beyond.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Hoy, S.M. Nusinersen: First Global Approval. Drugs 77, 473–479 (2017). https://doi.org/10.1007/s40265-017-0711-7

Download citation

Keywords

  • Spinal Muscular Atrophy
  • Survival Motor Neuron
  • Sham Procedure
  • Spinal Muscular Atrophy Patient
  • Motor Milestone