Dados do Trabalho

Título

FIREFISH 5yr FIREFISH Parts 1 and 2: 5-year efficacy and safety of risdiplam in Type 1 SMA

Introdução

Risdiplam (EVRYSDI®) is a centrally and peripherally distributed, oral survival of motor neuron
2 (SMN2) pre-mRNA splicing modifier, approved in over 100 countries worldwide.

Objetivo

FIREFISH (NCT02913482) is a multicenter, open-label, two-part study of risdiplam in children
with Type 1 spinal muscular atrophy (SMA) and two SMN2 gene copies (inclusion criteria: 1–7
months old at enrollment).

Método

In the dose-finding Part 1 of FIREFISH the safety, tolerability, and
pharmacokinetics/pharmacodynamics of different risdiplam doses were assessed. The pivotal
Part 2 assessed the safety and efficacy of risdiplam over 24 months at the dose selected from
Part 1. Thereafter, children entered a 3-year open-label extension phase and continued to
receive risdiplam at the pivotal dose.

Resultados

The FIREFISH results after 4 years of risdiplam treatment showed that 91% of children were
alive and 81% were alive and did not require permanent ventilation. Additionally, children either
maintained or improved their motor skills in terms of developmental milestones and motor
function, which is not observed in the natural history of Type 1 SMA.
Pooled safety and efficacy data were available from 58 enrolled infants who completed
risdiplam treatment over a period of 5 years (Part 1 high-dose cohort, n=17; Part 2, N=41). The
last FIREFISH patient completed their final assessment after 5 years of risdiplam treatment at
the pivotal dose on December 22, 2023. Here we present the final pooled safety and efficacy
results from the FIREFISH study after 5 years of risdiplam treatment.

Conclusão

FIREFISH Parts 1 and 2 provide long-term clinical trial safety and efficacy data on risdiplam in
the treatment of Type 1 SMA.

Referências

Masson R, Mazurkiewicz-Bełdzińska M, Rose K, Servais L, Xiong H, Zanoteli E, Baranello G, Bruno C, Day JW, Deconinck N, Klein A, Mercuri E, Vlodavets D, Wang Y, Dodman A, El-Khairi M, Gorni K, Jaber B, Kletzl H, Gaki E, Fontoura P, Darras BT; FIREFISH Study Group.Safety and efficacy of risdiplam in patients with type 1 spinal muscular atrophy (FIREFISH part 2): secondary analyses from an open-label trial. Lancet Neurol. 2022 Dec;21(12):1110-111

Palavras Chave

Risdiplam; Spinal muscular atrophy; SMN1