Dados do Trabalho

Título

RAINBOWFISH: 2-year efficacy and safety data of risdiplam in infants with presymptomatic SMA

Introdução

Risdiplam (EVRYSDI ® ) is a centrally and peripherally distributed, oral survival of motor neuron 2
(SMN2) pre‑mRNA splicing modifier that has been widely approved for the treatment of spinal
muscular atrophy (SMA).

Objetivo

RAINBOWFISH (NCT03779334) is a global, open-label, single-arm, multicentre, Phase 2 study
assessing the efficacy, safety and pharmacokinetics/pharmacodynamics of risdiplam in infants with
genetically diagnosed and presymptomatic SMA from birth to 6 weeks of age (at first dose),
regardless of SMN2 copy number.

Método

The study enrolled 26 infants: eight infants had two SMN2 copies, 13 infants had three SMN2 copies
and five infants had ≥4 SMN2 copies. The primary efficacy (PE) population (n=5) had two SMN2 copies and baseline compound muscle action potential (CMAP) amplitudes ≥1.5mV. Drug dosage
was adjusted to achieve a target exposure of approximately 2,000 ng∙ hr/mL.

Resultados

The primary endpoint was met after 12 months of risdiplam treatment with 4/5 (80%) infants in the PE
population able to sit without support for ≥5 seconds (Item 22 of the Gross Motor Scale of the Bayley
Scales of Infant and Toddler Development, third edition [BSID-III]). Irrespective of CMAP amplitude,
7/8 infants with two SMN2 copies were able to sit without support for ≥30 seconds (BSID‑III Item 26),
including all infants with CMAP amplitude <1.5 mV (n=3). Out of 26 infants, 24 (92%) were able to sit
without support, 13 (50%) were able to stand unaided and 12 (46%) were able to walk independently
at Month 12, as assessed by the Hammersmith Infant Neurological Examination, Module 2.
At Month 12, all infants were alive without permanent ventilation, maintained their swallowing and
feeding abilities and no adverse events (AEs) led to withdrawal or treatment discontinuation. Most
AEs were not considered treatment-related and resolved over time. One infant met the criteria for
development of clinically manifested SMA.

Conclusão

Here we report the 2-year efficacy and safety data from RAINBOWFISH.

Referências

Darras BT, Masson R, Mazurkiewicz-Bełdzińska M, Rose K, Xiong H, Zanoteli E, Baranello G, Bruno C, Vlodavets D, Wang Y, El-Khairi M, Gerber M, Gorni K, Khwaja O, Kletzl H, Scalco RS, Fontoura P, Servais L; FIREFISH Working Group.Risdiplam-Treated Infants with Type 1 Spinal Muscular Atrophy versus Historical Controls. N Engl J Med. 2021 Jul 29;385(5):427-43

Palavras Chave

Risdiplam; spinal muscularatrophy; SMN1