Finkel RS, Mercuri E, Darras BT, Connolly AM, Kuntz NL, Kirschner J, Chiriboga CA, Saito K, Servais L, Tizzano E, Topaloglu H, Tulinius M, Montes J, Glanzman AM, Bishop K, Zhong ZJ, Gheuens S, Bennett CF, Schneider E, Farwell W, De Vivo DC; ENDEAR Study Group.
N Engl J Med. 2017 Nov 2;377(18):1723-1732

Prof. Richard Finkel

No one in the field of oligonucleotide therapeutics should have missed the impressive results achieved with nusinersen (now commercialized as Spinraza) in the treatment of Spinal Muscular Atrophy (SMA). These have previously been discussed in detail as part of the OTS “Perspectives on current Science” series (here and here).

Here is a quick explanation of how nusinersen works:

Prof. Richard Finkel, the lead investigator for a number of the nusinersen clinical trials, has already received the OTS “Paper of the Year 2017” award for his publication on the phase II study of nusinersen in infantile onset SMA. Please see his award lecture:

In this paper, Prof. Finkel and his collaborators from the ENDEAR study group report the final results from the follow-on phase III trial NCT02193074. This trial was terminated early, and all patients rolled over onto open-label nusinersen treatment in the extension study (SHINE, NCT02594124), after a significantly higher number of patients in the nusinersen-treated group had a motor milestone response at a pre-specified interim analysis (41% vs 0%). In the final analysis of ENDEAR, 51% of nusinersen-treated infants had a motor-milestone response versus none in the control group (n=73 vs n=37). The median time to death or permanent ventilation was not reached in the treatment group but was 22.6 weeks in the control group.

Why you should read it

The clinical trial described here was one of the two registration studies that led to the accelerated approval of nusinersen. Nusinersen (Spinraza) is a transformative treatment for SMA that has put oligonucleotide therapeutics back in the spotlight.