Slide 1: FIREFISH Parts 1 and 2: 5-year efficacy and safety of risdiplam in Type 1 SMA
FIREFISH Parts 1 and 2: 5-year efficacy and safety of risdiplam in Type 1 SMA Maria Mazurkiewicz-Bełdzińska,1* Giovanni Baranello,2,3 Odile Boespflug-Tanguy,4,5 John W Day,6 Nicolas Deconinck,7,8 Andrea Klein,9,10 Riccardo Masson,3 Eugenio Mercuri,11 Kristy Rose,12 Laurent Servais,13,14 Dmitry Vloda
Slide 2: Disclosures
Disclosures MMB has received speaker honoraria and payment for serving on advisory boards for F. Hoffmann-La Roche, Sanofi, Novartis, Biogen, and UCB. GB has received speaker and consultancy honoraria from AveXis, Roche, PTC Therapeutics, and Sarepta Therapeutics. He has received fees for servin
Slide 3: FIREFISH: Risdiplam treatment for Type 1 SMA
FIREFISH: Risdiplam treatment for Type 1 SMA Risdiplam (EVRYSDI®)* is a centrally and peripherally distributed oral SMN2 pre-mRNA splicing modifier1,2 Risdiplam is an oral medicine that crosses the blood-brain barrier Risdiplam uniformly distributes to the central nervous system and peripheral t
Slide 4: Study design
FIREFISH: Study design FIREFISH (NCT02913482) was an open-label, multicenter clinical study that assessed the safety, tolerability, PK, PD, and efficacy of risdiplam in infants with Type 1 SMA END OF THE STUDY PRIMARY ANALYSIS December 22, 2023 Screening Year 1 Year 2 Year 5 Part 1: Dose finding (n=
Slide 5: Patient disposition
FIREFISH: Patient disposition A total of 49 children from the FIREFISH Part 1 and 2 pooled population completed the 5-year study period END OF THE STUDY PRIMARY ANALYSIS December 22, 2023 Screening Year 1 Year 2 Year 5 Part 1: n=17 Pooled population Pooled population OLE (3 years) Part 2: n=41 Poole
Slide 6: Baseline characteristics
FIREFISH pooled population: Baseline characteristics At enrollment, the majority of infants had experienced >3 months of symptomatic Type 1 SMA and had impaired motor function FIREFISH Part 1 FIREFISH Part 2 All children Baseline demographics (n=17) (n=41) (N=58) Gender, n (%) Female/male 11 (65)/6
Slide 7: Event-free survival compared with natural history
FIREFISH pooled population: Efficacy endpoint After 5 years of risdiplam treatment, event-free* survival was greatly improved in treated children compared with natural history 100 100 Probability of endpoint-free‡ Proportion event free* (%) 80 80 survival (%) 60 60 Population All children (N=58) 40
Slide 8: BSID-III: ability to sit without support
FIREFISH pooled population: Efficacy endpoint The majority of children treated with risdiplam over 5 years achieved and maintained the ability to sit without support* Year 1 Year 5 BSID-III (primary analysis) (end of the study) Sitting† 19/58 36/58 Without support for 5 seconds 33% 62% Sitting‡ 11/5
Slide 9: HINE-2 motor milestones
FIREFISH pooled population: Efficacy endpoint The majority of children treated with risdiplam over 5 years maintained or continued to achieve motor milestones* Year 1 Year 5 (primary analysis) (end of the study) 27/58 40/58 HINE-2 Head control ‘All the time maintained upright’ 47% 69% Untreated chil
Slide 10: Swallowing/Feeding
FIREFISH pooled population: Efficacy endpoint The majority of children treated with risdiplam over 5 years maintained swallowing and feeding abilities Swallowing/Feeding Year 1* Year 5 (primary analysis) (end of the study) Ability to swallow† 50/53 46/48 94% 96% Ability to feed orally‡ 49/54 42/46 9
Slide 11: CHOP-INTEND total score
FIREFISH pooled population: Efficacy endpoint Children treated with risdiplam over 5 years showed sustained improvements in CHOP-INTEND total score PRIMARY ANALYSIS END OF THE STUDY CHOP-INTEND Year 1 Year 5 Untreated Pooled population* OLE children with Type 1 SMA Mean CHOP-INTEND total score (±SD)
Slide 12: Hospitalizations declined over the 5-year treatment period
FIREFISH pooled population: Efficacy endpoint Hospitalizations* declined over the 5-year risdiplam treatment period Years 0–1 1.24 In natural history, children with Type 1 SMA Hospitalizations experienced between Years 0–2 0.92 ~4.2 and 7.6 per PY hospitalizations every year1,2 Years 0–3 0.71 13/58
Slide 13: No AEs led to withdrawal or discontinuation of risdiplam
FIREFISH pooled population: Safety endpoint No AEs led to withdrawal or discontinuation of risdiplam treatment over the 5-year study period All patients AEs* (N=58) Total number of AEs 879 Total number of deaths, n (%) 6 (10) No new safety signals AE 58 (100) were observed in the AE leading to withd
Slide 14: Most common AEs and SAEs over the 5-year study period
FIREFISH pooled population: Safety endpoint The most common AEs and SAEs over the 5-year study period were attributed to the MedDRA SOC: Infections and infestations All patients (N=58) Upper respiratory tract infection 37 (64) Pyrexia 37 (64) Pneumonia 29 (50) Skin events were Nasopharyngitis 16 (28
Slide 15: Rate of AEs decreased after the first year
FIREFISH pooled population: Safety endpoint The rate of AEs decreased after the first year of risdiplam treatment and stabilized up to Year 5 800 614.67 600 AEs per 100PY (90% CI) 437.07 COVID-19 restrictions The overall rate of 400 AEs decreased by 66% between Year 1 and the final year of 214.26 21
Slide 16: Rate of SAEs decreased after the first year
FIREFISH pooled population: Safety endpoint The rate of SAEs decreased after the first year of risdiplam treatment and stabilized up to Year 5 150 SAEs 105,17 MedDRA SOC: Infections and infestations The overall rate of SAEs per 100PY (90% CI) SAEs decreased by 100 73% between Year 1 COVID-19 restric
Slide 17: Conclusions
FIREFISH pooled population: Conclusions At the end of the 5-year FIREFISH study, children with symptomatic Type 1 SMA showed improvement or stabilization in disease-related outcomes 91% of children The majority of The majority of No The rates of AEs were alive and 81% children achieved children trea
Slide 18: Thank you to all the patients, families, and healthcare professionals
Thank you to all the patients, families, healthcare professionals and patient organizations who contributed to the success of the FIREFISH trial Mar 2021 Risdiplam was approved by the EC Nov 2019 Primary efficacy endpoint was met (FIREFISH Part 2) Dec 2023 Last patient Nov 2020 completes 5 years Pat
Slide 19: Supplementary Material
Supplementary Material In collaboration with and 19 © 2023 F. Hoffmann-La Roche Ltd. All rights reserved
Slide 20: Children with permanent ventilation had improvements or maintenance in motor function scores
FIREFISH pooled population: Supplementary material Children with symptomatic Type 1 SMA and permanent ventilation* had improvements or maintenance in motor function scores Six children met the definition of permanent ventilation up to Year 5 Patient Permanent Tracheostomy CHOP-INTEND HINE-2 score