Clinical Evidence Supporting Early Treatment Of Patients With Spinal Muscular Atrophy: Current Perspectives

Figures & data

Table 1 Summary of the different studies supporting better efficacy of early treatment

		Nusinersen	Zolgensma	Risdiplam	Branaplam
SMA1	Study phase completed	Phase 3 ENDEAR: NCT02193074 (^Citation12)
		Phase 4 EAP: NCT02865109 (^Citation19,Citation18)
	Study phase ongoing	Phase 3 SHINE: NCT02594124 (^Citation28)	Phase 1 NCT NCT03421977 (^Citation22, ^Citation26, ^Citation32)	Phase 2-3 FIREFISH: NCT02913482 (^Citation34)	Phase 1-2 NCT02268552 (^Citation36)
		Phase 3 STR1VE: NCT03306277; STR1VE EU: NCT03461289 (^Citation21)
	Blinding	Double-blinded, placebo-controlled (^Citation12)	Open-label studies	Open-label study	Open-label study
		Open-label study (survivors from ENDEAR)(^Citation28)
		Open-label study (^Citation19,Citation18)
	Status	Terminated, peer-reviewed (^Citation12)	Published peer-reviewed (^Citation22, ^Citation26)	Ongoing, presented	Ongoing, presented
		Ongoing, presented (^Citation28)
		Peer-review (^Citation18,Citation19)	Presented (^Citation32, ^Citation21)
	Outcome	≥ 2 points on HINE scale at day 394 ; time to death or permanent ventilation at day 394 (^Citation12)	Time to reach 40 points on CHOP INTEND; age at sitting position	Acquisition of sitting position	Increase in CHOP INTEND
		CHOP INTEND after 1058 days of treatment; sitting position after 240 days on modified maintenance dosing regimen, assisted walking (^Citation28)
		≥ 4 points increase on CHOP INTEND (^Citation19)
		Increase in CHOP INTEND (^Citation18)
	Number of patients and age at treatment initiation and analysis	80 patients on nusinersen (39 patients with disease duration <13.1 weeks and 41 patients > 13.1) (^Citation12)	12 patients (6 patients < 3 months at treatment and 6 > 6 months	14 patients (4 patients < 5 months at treatment initiation and 10 patients > 5 months)	8 patients (4 patients < 4 months at treatment initiation and 4 patients > 4 months(8 patients followed for at least 85 days)
		41 patients (22 patients < 5.42 months at treatment initiation and 19 patients > 5.42 and ≤ 7.96 months) (^Citation28)
		104 patients (9 patients < 7 months at treatment initiation and 95 patients > 7 months) (^Citation19)
		61 patients (17 patients < 7 months at treatment initiation and 44 > 7 months) (^Citation18)
	Cut off	394 days post the first injection (^Citation12)	18 months	8 months	85 days
		1058 days post the first injection (^Citation28)
		180 days post the first injection (^Citation19)
		180 days post the first injection (^Citation18)
SMA2	Study phase completed	Phase 3 CHERISH: NCT02292537 (^Citation13)
	Study phase ongoing	Phase 3 SHINE: NCT 02594124 (^Citation29)		Phase 2, 3 SUNFISH: NCT02908685 (^Citation35)
	Blinding	Double-blind, placebo-controlled (^Citation13)		Double-blind, placebo-controlled
		Open label study (^Citation29)
	Status	Completed, peer-reviewed (^Citation13)		Ongoing, presented
		Ongoing, presented (^Citation29)
	Outcome in SMA2	Increase ≥ 3 points on HFMSE at 15 months treatments (^Citation13)		Increase in MFM 32 in 1 year
		Increase in HFSME and in RULM score (^Citation29)
	Number of patients and age at treatment initiation and analysis	66 patients with nusinersen / 59 patients under 6 years of age at treatment initiation (^Citation13)		43 patients (19 > 11 years and 24 aged 2-11 years)
		110 patients (39 < 3.69 year at treatment initiation, 35 aged > 3.69 and < 4.92 years and 36 > 4.92 years) (^Citation29)
	Cut off	15 month of treatment (^Citation13)		1 year
		690 days of treatment (^Citation29)
PRE-SYMPTOMATIC	Study phase completed
	Study phase ongoing	Phase 2 NURTURE: NCT02386553 (^Citation30)	Phase 1 SPR1NT: NCT03505099 (^Citation33)
	Blinding	Open-label study	Open-label study
	Status	Ongoing, presented	Ongoing, presented
	Outcome in Pre-symptomatic SMA	Non permanent ventilation, acquisition of sitting position,acquisition of walking with assistance, acquisition of independent walking	Score on CHOP INTEND
	Number of patients and age at treatment initiation and analysis	22 Newborns < 6 weeks	18 Newborns < 6 weeks
	Cut off	14 -34 months	0.8-9.1 months follow-up

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