RAINBOWFISH: Primary efficacy and safety data in risdiplam-treated infants with presymptomatic spinal muscular atrophy (SMA)

Enrico Bertini

RAINBOWFISH: Primary efficacy and safety data in risdiplam-treated infants with presymptomatic spinal muscular atrophy (SMA)

Autori

RICHARD S FINKEL (CENTER FOR EXPERIMENTAL NEUROTHERAPEUTICS, ST JUDE CHILDREN’S RESEARCH HOSPITAL, MEMPHIS, TN, USA – NEUROPSICHIATRA INFANTILE);
MICHELLE A FARRAR (SYDNEY CHILDREN’S HOSPITAL NETWORK AND UNSW MEDICINE, UNSW SYDNEY, SYDNEY, AUSTRALIA – NEUROPSICHIATRA INFANTILE);
LAURENT SERVAIS (MDUK OXFORD NEUROMUSCULAR CENTRE, DEPARTMENT OF PAEDIATRICS, UNIVERSITY OF OXFORD, OXFORD, UK; DIVISION OF CHILD NEUROLOGY, CENTRE DE RÉFÉRENCES DES MALADIES NEUROMUSCULAIRES, DEPARTMENT OF PEDIATRICS, UNIVERSITY HOSPITAL LIÈGE & UNIVERSITY OF LIÈGE, LIÈGE, BELGIUM; I-MOTION INSTITUT DE MYOLOGIE AP-HP, HÔPITAL ARMAND TROUSSEAU, PARIS, FRANCE – NEUROPSICHIATRA INFANTILE);
DMITRY VLODAVETS (RUSSIAN CHILDREN NEUROMUSCULAR CENTER, VELTISCHEV CLINICAL PEDIATRIC RESEARCH INSTITUTE OF PIROGOV RUSSIAN NATIONAL RESEARCH MEDICAL UNIVERSITY, MOSCOW, RUSSIA – NEUROPSICHIATRA INFANTILE);
EDMAR ZANOTELI (DEPARTMENT OF NEUROLOGY, FACULDADE DE MEDICINA, UNIVERSIDADE DE SÃO PAULO, SÃO PAULO, BRAZIL – NEUROLOGO);
MOHAMMED AL-MUHAIZEA (DEPARTMENT OF NEUROSCIENCES, KING FAISAL SPECIALIST HOSPITAL & RESEARCH CENTER-RIYADH, RIYADH, KINGDOM OF SAUDI ARABIA – NEUROPSICHIATRA INFANTILE);
ALEXANDRA PRUFER (FEDERAL UNI RIO DE JANEIRO, RIO DE JANEIRO, BRAZIL – NEUROPSICHIATRA INFANTILE);
LESLIE NELSON (UT SOUTHWESTERN MEDICAL CENTER, DALLAS, TX, USA – FISIOTERAPISTA);
CAROLYN FISCHER (ROCHE PRODUCTS LTD, WELWYN GARDEN CITY, UK – DATA SCIENTIST);
MARIANNE GERBER (PHARMA DEVELOPMENT, SAFETY, F. HOFFMANN-LA ROCHE LTD, BASEL, SWITZERLAND – SAFETY SCIENTIST);
KSENIJA GORNI (PDMA NEUROSCIENCE AND RARE DISEASE, F. HOFFMANN-LA ROCHE LTD, BASEL, SWITZERLAND – NEUROPSICHIATRA INFANTILE);
HEIDEMARIE KLETZL (ROCHE PHARMACEUTICAL RESEARCH AND EARLY DEVELOPMENT, ROCHE INNOVATION CENTER BASEL, BASEL, SWITZERLAND – CLINICAL PHARMACOLOGIST);
LAURA PALFREEMAN (ROCHE PRODUCTS LTD, WELWYN GARDEN CITY, UK – CLINICAL SCIENTIST);
ELENI GAKI (ROCHE PRODUCTS LTD, WELWYN GARDEN CITY, UK – CLINICAL SCIENTIST);
PAULO FONTOURA (PDMA NEUROSCIENCE AND RARE DISEASE, F. HOFFMANN-LA ROCHE LTD, BASEL, SWITZERLAND – NEUROLOGIST);
ENRICO BERTINI (RESEARCH UNIT OF NEUROMUSCULAR AND NEURODEGENERATIVE DISORDERS, BAMBINO GESÙ CHILDREN’S RESEARCH HOSPITAL IRCCS, ROME, ITALY – NEUROPSICHIATRA INFANTILE);
ON BEHALF OF THE RAINBOWFISH STUDY GROUP

Presentatore

ENRICO BERTINI (RESEARCH UNIT OF NEUROMUSCULAR AND NEURODEGENERATIVE DISORDERS, BAMBINO GESÙ CHILDREN’S RESEARCH HOSPITAL IRCCS, ROME, ITALY)

Modalità

Oral Communication

Abstract

Risdiplam (EVRYSDI®) is a centrally and peripherally distributed, oral survival of motor neuron 2 (SMN2) pre‑mRNA splicing modifier.
RAINBOWFISH (NCT03779334) is an open-label, single-arm, multicenter study assessing the efficacy, safety and PK/PD of risdiplam in infants with genetically diagnosed and presymptomatic spinal muscular atrophy (SMA) from birth–6 weeks of age (at first dose), regardless of SMN2 copy number.
The primary endpoint is the proportion of infants, with two SMN2 copies and baseline CMAP amplitude ≥1.5mV, who are able to sit without support for ≥5 seconds (assessed by Item 22 of the Gross Motor Scale of the Bayley Scales of Infant and Toddler Development, third edition). Secondary endpoints include: the development of clinically manifested SMA; survival and permanent ventilation; motor milestone achievement; motor function; growth measures; nutritional status; CMAP; PK/PD; and safety monitoring.
The median age at first dose was 26.5 days (range: 16–40 days) for the first 18 enrolled infants. No treatment-related serious adverse events were reported in infants treated for ≤22.8 months. A preliminary analysis of seven infants treated for ≥12 months demonstrated that most reached near maximum scores on the CHOP INTEND scale by 4–5 months of age and achieved motor milestones within WHO windows for healthy children. All seven infants treated for ≥12 months were alive without permanent ventilation, maintained swallowing and feeding abilities, and had not required hospitalization. Here we report for the first-time results from the RAINBOWFISH primary analysis conducted at Month 12.