Nusinersen / ENDEAR3434. Finkel RS, Mercuri E, Darras BT, Connolly AM, Kuntz NL, Kirschner J et al. Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy. N Engl J Med. 2017 Nov;377(18):1723-32. https://doi.org/10.1056/NEJMoa1702752
https://doi.org/10.1056/NEJMoa1702752...
|
SMA1 / ≤ 6 months / 2 copies |
121 infants / placebo-controlled / phase 3 |
HINE, CHOP-INTEND |
51% of the patients had HINE improvement; major efficacy when illness duration < 12 weeks |
Nusinersen / CHERISH3535. Mercuri E, Finkel RS, Kirschner J, Chiriboga C, Kuntz N, Sun P et al. Efficacy and safety of nusinersen in children with later-onset spinal muscular atrophy (SMA): end of study results from the phase 3 CHERISH study. Neuromuscul Disord. 2017;27 Suppl. 2:S210. https://doi.org/10.1016/j.nmd.2017.06.418
https://doi.org/10.1016/j.nmd.2017.06.41...
|
SMA2 and 3 / 2 to 12 years / 2 or 3 copies |
126 patients / placebo-controlled / phase 3 |
HFMSE |
57.3% of the patients had at least 3 points higher score in HFMSE |
Nusinersen / NURTURE3636. Hwu WL, De Vivo DC, Bertini E, Foster R, Gheuens S, Farwell W et al. Outcomes after 1-year in presymptomatic infants with genetically diagnosed spinal muscular atrophy (SMA) treated with nusinersen: interim results from the NURTURE study. Neuromuscul Disord. 2017;27 Suppl. 2:S212. https://doi.org/10.1016/j.nmd.2017.06.424
https://doi.org/10.1016/j.nmd.2017.06.42...
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Presymptomatic / 2 or 3 copies |
20 infants / phase 2 |
HINE, WHO motor milestones |
No patient died or needed ventilatory support, all achieved some of the expected HINE motor milestones for healthy infants based on age; |
Nusinersen / SHINE, NCT02594124 |
SMA patients from other nusinersen studies |
Open label / extension study |
|
Ongoing |
AVXS-1014242. Mendell JR, Al-Zaidy S, Shell R, Arnold WD, Rodino-Klapac LR, Prior TW et al. Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy. N Engl J Med. 2017 Nov;377(18):1713-22. https://doi.org/10.1056/NEJMoa1706198
https://doi.org/10.1056/NEJMoa1706198...
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SMA1 / < 6 months / 2 copies |
15 infants / open label / phase 1-2 |
Safety and tolerability; death or permanent ventilation; ability to sit; CHOP-INTEND |
Positive impact on the survival and on motor function; 11/12 patients achieved motor milestones not seen in this population; results depended on age at onset and basal motor function |
AVXS-101 / STR1VE, NCT03306277 |
SMA 1 / < 6 months / 1 or 2 copies |
Open label / phase 3 |
Achievement of independent sitting; event-free survival |
Ongoing |
RO7034067 / FIREFISH, NCT02913482 |
SMA1 / 1-7months / 2 copies |
Open label / phase 2 |
Safety; sitting without support (BSID-III) |
Ongoing |
RO7034067 / SUNFISH, NCT02908685 |
SMA2 and 3 / 2 to 25 years |
Placebo-controlled / phase 2 |
Safety; MFM-32 |
Ongoing |
Branaplam / LMI070X2201, NCT02268552 |
SMA1 / 1-7 months |
Phase 1/2 |
|
Ongoing |
Olesoxime / TRO196224444. Bertini E, Dessaud E, Mercuri E, Muntoni F, Kirschner J, Reid C et al. Safety and efficacy of olesoxime in patients with type 2 or non-ambulatory type 3 spinal muscular atrophy: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol. 2017 Jul;16(7):513-22. https://doi.org/10.1016/S1474-4422(17)30085-6
https://doi.org/10.1016/S1474-4422(17)30...
|
SMA2 or 3 / 3 to 25 years |
165 patients / controlled / Phase 2 |
MFM |
Primary endpoint not met. Patients were stable compared to placebo. |
Olesoxime / NCT02628743 |
SMA 2 or 3 / 3 to 25 years |
Open label / Phase 2 |
MFM |
Ongoing |
CK-2127107 / NCT02644668 |
SMA 2 to 4 / > 12years |
Placebo-controlled / phase 2 |
HFMS-E, 6MWT, FVC |
Ongoing |