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P.060 Time to treatment effect in Spinal Muscular Atrophy Type 1 (SMA1): an indirect comparison of treatments

Published online by Cambridge University Press:  05 June 2019

RS Finkel
Affiliation:
(Orlando)
O Dabbous
Affiliation:
(Bannockburn)
R Arjunji
Affiliation:
(Bannockburn)
M Droege
Affiliation:
(Bannockburn)
DE Feltner
Affiliation:
(Bannockburn)
A Novack
Affiliation:
(Bannockburn)
M Menier
Affiliation:
(Bannockburn)
DM Sproule
Affiliation:
(Bannockburn)
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Abstract

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Background: SMA1 is a rapidly progressing disease resulting in death/permanent ventilation by 2 years. This study compared clinical trial data evaluating the relationship between treatment timing, time to treatment effect, and clinical outcomes in SMA1 patients Methods: A post-hoc indirect treatment comparison was conducted to measure time-to-effect differences in AVXS-101 (CL-101, NCT02122952, cohort 2) vs nusinersen (ENDEAR, NCT02193074) or risdiplam (FIREFISH, NCT02913482) using CHOP-INTEND scores. Results: Compared with nusinersen, AVXS-101 more rapidly increased mean CHOP-INTEND score from baseline (9.8- and 14.9-point increase at 1- and 2-months post-AVXS-101 vs ≤5-point increase at 2-months post-nusinersen). Greater survival benefits and lower rates of permanent ventilatory support were also observed in AVXS-101- vs nusinersen-treated patients. Compared with risdiplam treatment, AVXS-101 improved median CHOP-INTEND scores (14.0-point increase at 2-months post-AVXS-101 vs 5.5-point increase at ~2-months post-risdiplam). Treatment differences were maintained through 8-months with additional improvements at all time-points. Conclusions: Although patients in these 3 cohorts are not entirely matched (e.g. age, disease severity), useful comparisons can still be made. Based on CHOP-INTEND scores, the treatment effect of AVXS-101 appears to be more rapid vs nusinersen or risdiplam. These findings suggest that timely restoration of SMN protein may be essential for maximizing outcomes in SMA1 patients.

Type
Poster Presentations
Copyright
© The Canadian Journal of Neurological Sciences Inc. 2019