Spinal muscular atrophy: Where are we now? Current challenges and high hopes

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Summary of risdiplam clinical trials Roche_ Roche announces 2-year risdiplam data from SUNFISH and new data from JEWELFISH in infants, children and adults with spinal muscular atrophy (SMA) [29, 30, 31, 32, 33] SMN1- survival of motor neuron; SMN2- survival of motor neuron 2; MFM- Motor Function Measure

Clinical trial	Identification number	Characteristics	Patients profile	Main purpose of study	Current status of study
FIREFISH	NCT02913482	Two-part, open label study.	Infants aged 1–7 months of age with SMA type I and two SMN2 gene copies.	Part one: dose-escalation studyPart two: investigation of efficiency at the dose selected in the first part.	The study met its primary endpoint.
SUNFISH	NCT02908685	Two-part, double blind, placebo-controlled study.	People between 2–25 years old with SMA type II or III.	Part one: dose-escalation studyPart two: motor function evaluation using total score of MFM.	The study met its primary endpoint.
JEWELFISH	NCT03032172	Open-label exploratory trial.	People between 6 months – 60 years, previously treated with SMA-directed therapies	Safety and tolerability of daily risdiplam dose in non-naïve patients who have taken nusinersen, olesoxime or onasemnogene abeparvovec-xioi.	The study has completed recruitment.
RAINBOWFISH	NCT03779334	Single-arm, multicentre study.	Babies from birth to six weeks of age (at first dose) with genetically diagnosed SMA, without symptoms.	Efficacy, safety, pharmacokinetics and pharmacodynamics.	The study is currently in phase 2. No results were published yet.

Summary of approved therapeutics and substances under clinical trials for SMA [20, 23, 24, 28, 35, 36, 38]

Therapeutic	Management company	Characteristics	Patient's profile	Dosage and administration
Spinraza**	Biogen	Survival motor neuron 2 (SMN2) splicing modifier	All ages and types	Administered by intrathecal injection at an equivalent dose of 12 mg (4–5 ml based on age)
Zolgensma**	Novartis Gene Therapies*	Gene therapy based on using recombinant adeno-associated virus subtype 9 (AAV9) to overexpression SMN1 gene	Less than two years old paediatric patients with spinal muscular atrophy and bi-allelic mutations in the SMN1 gene	One intravenous infusion; dosage based on patient's body weight
Evrysdi**	Roche, Genetech Inc.	Survival motor neuron 2 (SMN2) splicing modifier	Patients 2 months of age and older suffering from SMA	Administrated orally once a day; dosage is determined by patient age and body weight
Reldesemtiv	Cytokinetics/Astellas	Muscle drug (non-SMN)	Patients with SMA types 2, 3 and 4 who are age 12 or older	Administrated orally; phase 2 trial completed
Apitegromab	Scholar Rock	Muscle drug (non-SMN)	Patient between 2 and 21 who have SMA type 2 or 3.	Administrated by intravenous infusion; phase 2 trial ongoing