Roche Holding Ltd · SIX:RO
Roche — World Muscle Society Congress 2024
19 slides from Roche's conference presentation, 2024
Slide 1: RAINBOWFISH: 2-year efficacy and safety data of risdiplam in infants with presymptomatic SMA
RAINBOWFISH: 2-year efficacy and safety data of risdiplam in infants with presymptomatic SMA Laurent Servais,1,2* Richard S Finkel,3* Dmitry Vlodavets,4 Edmar Zanoteli,5 Mohammad Al-Muhaizea,6 Alexandra Prufer de Queiroz Campos Araújo,7 Leslie Nelson,8 Birgit Jaber,9 Ksenija Gorni,10 Heidemarie Klet
Slide 2: Disclosures
Disclosures Laurent Servais is a principal investigator of SMA studies for F. Hoffmann-La Roche Ltd, Biogen and AveXis; he has attended scientific advisory boards of F. Hoffmann-La Roche Ltd, Biogen and AveXis and received consultancy fees from Biogen; he serves on the board for Cytokinetics; he is
Slide 3: Background
Background In patients with SMA, motor neuron degeneration begins before the onset of symptoms1,2 In clinical studies earlier treatment initiation in symptomatic patients has been established as predictive of improved outcomes3 The timing of treatment initiation is crucial Risdiplam* is a centra
Slide 4: RAINBOWFISH: multicentre, open-label, single-arm study design
RAINBOWFISH: A multicentre, open-label, single-arm study of risdiplam in infants with genetically diagnosed, presymptomatic SMA PRIMARY EFFICACY ANALYSIS Screening Year 1 Year 2 Risdiplam Open-label extension (≥3 years) Inclusion criteria: N=26 Genetic diagnosis of 5q-autosomal Primary endpoint (n=5
Slide 5: Infants enrolled had 2 to ≥4 SMN2 copies and wide range of CMAP amplitudes
Infants enrolled in RAINBOWFISH had 2 to ≥4 SMN2 copies and a wide range of CMAP amplitudes at baseline Intent-to-treat population (including primary efficacy population*) All infants Baseline characteristics (N=26) SMN2 copy number 2 3 ≥4 (n=8) (n=13) (n=5) Age at first dose, days, median (range) 2
Slide 6: 23 infants completed 2 years of risdiplam treatment
23 infants completed 2 years of risdiplam treatment during the RAINBOWFISH study PRIMARY EFFICACY ANALYSIS Screening Year 1 Year 2 Risdiplam Open-label extension (≥3 years) 2 SMN2 copies (n=5) ITT population N=26 Completed Completed Baseline CMAP amplitude ≥1.5 mV (n=4) Baseline CMAP amplitude <1.5
Slide 7: Majority of infants at Year 2 able to sit and walk alone, BSID-III
The majority of infants who performed the Year 2 assessment were able to sit and walk alone, as assessed by the BSID-III* Sitting without Sitting without support for 5 s‡ support for 30 s§ Standing alone‖ Walking alone¶ 2 SMN2 copies 5/5 5/5 3/5 3/5 n=5† infants infants infants infants 3 SMN2 copies
Slide 8: All infants with 2 SMN2 copies who performed Year 2 assessment could sit
All infants with 2 SMN2 copies who performed the Year 2 assessment could sit without support and most were able to stand and walk alone Walking alone Sitting without Standing Walking Support for ≥5 s† alone‡ alone§ Assessed by BSID-III* Standing alone Age at first Withdrawn WHO windows of dose (days
Slide 9: Most infants with 3 SMN2 copies achieved milestones within WHO windows
Most infants with 3 SMN2 copies achieved age-appropriate motor milestones within the WHO windows of typical development Walking alone Sitting without Standing Walking Assessed by BSID-III* Support for ≥5 s† alone‡ alone§ Standing alone Age at first WHO windows of dose (days) achievement in Sitting w
Slide 10: Most infants with ≥4 SMN2 copies achieved milestones within WHO windows
Most infants with ≥4 SMN2 copies achieved age-appropriate motor milestones within the WHO windows of typical development Walking alone Assessed by BSID-III* Sitting without Standing Walking Support for ≥5 s† alone‡ alone§ Standing alone Age at first WHO windows of dose (days) achievement in Sitting
Slide 11: Majority able to sit, stand and walk, as assessed by HINE-2
The majority of infants who performed the Year 2 assessment were able to sit, stand and walk, as assessed by the HINE-2 Sitting (pivots) Standing Walking 5/5 4/5 4/5† 2 SMN2 copies n=5* 1/5 ‘stands 2/5 with support’ ‘cruising’ 3/5 ‘stands 2/5 ‘walking unaided’ independently’ Sitting Standing Walking
Slide 12: Most infants did not exhibit clinically manifested SMA after 2 years
Most infants did not exhibit clinically manifested SMA after 2 years of risdiplam treatment Infants were considered to have developed clinically 6/26 infants met the criteria for manifested SMA at Year 2 if one of A or B were met: clinically manifested SMA (all had 2 SMN2 copies) A: Failure to achie
Slide 13: Majority of infants met CHOP-INTEND completion criteria by Year 2
The majority of infants met the CHOP-INTEND completion criteria by Year 2 22/23 infants met the CHOP-INTEND CHOP-INTEND completion completion criteria at Year 2 criteria: Able to sit without support at two consecutive visits* Achieved a CHOP-INTEND total 4/5 infants with 18/18 infants score of ≥
Slide 14: Infants maintained bulbar function and none required permanent ventilation
All infants who completed 2 years of risdiplam treatment maintained bulbar function and none required permanent ventilation Swallowing and Respiratory Speech feeding support All were able to No infants No abnormal swallow and required findings in speech feed permanent development* exclusively ventil
Slide 15: Infants showed cognitive skills typical of normal child development
Infants taking risdiplam showed cognitive skills typical of normal child development, as assessed by the BSID-III Cognitive Scale* Baseline 1 year 2 years 70 BSID-III Cognitive Scale raw score Raw and scaled scores were 60 similar across the three SMN2 copy number groups (median ±range) 50 Median sc
Slide 16: No treatment-related AEs leading to withdrawal or discontinuation up to Year 2
There have been no treatment-related AEs leading to withdrawal or treatment discontinuation up to Year 2* All infants (N=26) Total number of AEs 281 AE 25 (96) AE leading to withdrawal from treatment 0 AE leading to dose modification/interruption† 5 (19) SAE‡ 4 (15) There were no deaths Number of in
Slide 17: Majority of AEs not treatment related and resolved over time
The majority of AEs were not considered to be treatment related and resolved over time All infants (N=26) Teething 11 (42.3) Gastroenteritis 10 (38.5) COVID-19 9 (34.6) Diarrhoea 9 (34.6) Most common AEs, n (%)* Eczema 8 (30.8) 92% (24/26) of infants (reported in ≥5 infants) Pyrexia 8 (30.8) did not
Slide 18: Conclusions
Conclusions The majority of infants treated presymptomatically with risdiplam over 2 years achieved sitting without support, standing and walking motor milestones The majority of All infants with infants with There were no 2 SMN2 copies who ≥3 SMN2 copies Infants showed deaths and reached Year 2 ach
Slide 19: We thank the individuals with SMA, their families and investigators
We thank the individuals with SMA, their families and the investigators and trial staff involved in the RAINBOWFISH study. We would also like to thank our collaborators at PTC Therapeutics and the SMA Foundation. Please scan using your QR reader application to access the graphs and data presented in