The license to Biogen included licenses to intellectual property that Ionis had acquired from Cold Spring Harbor Laboratory and University of Massachusetts.In November 2016, the new drug application was accepted under the FDAs 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. It was approved by the FDA in December 2016 and by EMA in May 2017 as the first drug to treat SMA. Subsequently, nusinersen was approved to treat SMA in Canada (July 2017), Japan (July 2017), Brasil (August 2017), Switzerland (September 2017), and China (February 2019). Society and culture
Economics
Nusinersen list price in the USA is US$125,000 per injection which puts the treatment cost at US$750,000 in the first year and US$375,000 annually after that. According to The New York Times, this places nusinersen "among the most expensive drugs in the world".In October 2017, the authorities in Denmark recommended nusinersen for use only in a small subset of people with SMA type 1 (young babies) and refused to offer it as a standard treatment for all other people with SMA quoting an "unreasonably high price" compared to the benefit.Norwegian authorities rejected the funding in October 2017 because the price of the medicine was "unethically high".
People survive owing to low amounts of the SMN protein produced from the SMN2 gene. Nusinersen modulates alternative splicing of the SMN2 gene, functionally converting it into SMN1 gene, thus increasing the level of SMN protein in the CNS.The drug distributes to CNS and peripheral tissues.The half-life is estimated to be 135 to 177 days in cerebrospinal fluid (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. The primary route of elimination is likely by urinary excretion for nusinersen and its metabolites. Chemistry
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. History
Nusinersen was developed in a collaboration between Adrian Krainer at Cold Spring Harbor Laboratory and Ionis Pharmaceuticals (formerly called Isis Pharmaceuticals). Initial work of target discovery of nusinersen was done by Dr. Ravindra Singh and co-workers at the University of Massachusetts Medical School funded by Cure SMA.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.