Roche Holding Ltd · SIX:RO
Roche — AAN 2023
17 slides from Roche's conference presentation, 2023
Slide 1: SUNFISH Parts 1 and 2: 4-year efficacy and safety of risdiplam in Types 2 and 3 SMA
SUNFISH Parts 1 and 2: 4-year efficacy and safety of risdiplam in Types 2 and 3 spinal muscular atrophy (SMA) Laurent Servais,1-3* Maryam Oskoui,4 John W Day,5 Nicolas Deconinck,6,7 Elena S Mazzone,8 Andres Nascimento,9 Kayoko Saito,10 Carole Vuillerot,11,12 Giovanni Baranello,13,14 Odile Boespflug-
Slide 2: Disclosures
Disclosures ■ LS is a PI of SMA studies for F. Hoffmann-La Roche Ltd, Biogen, and AveXis; he has attended SAB of F. Hoffmann-La Roche Ltd, Biogen and AveXis and received consultancy fees from Biogen; he serves on the board for Cytokinetics; he is co-inventor in the patent 20190029605 (Method for est
Slide 3: Introduction
Introduction ▪ SMA is a severe, progressive neuromuscular disease leading to loss of motor function and reduced life expectancy 1 ▪ Risdiplam is a centrally and peripherally distributed oral SMN2 pre-mRNA splicing modifier that increases and sustains the levels of functional SMN protein2–5 and has b
Slide 4: A randomized, placebo-controlled, double-blind study with broad inclusion criteria and a large dataset
A randomized, placebo-controlled, double-blind study with broad inclusion criteria and a large dataset Week Month Month Month 12 12 24 48 Dose Part 1 finding Risdiplam Parts 1 Part 2 Risdiplam:placebo 2:1 Risdiplam Extension and 21 N=180 Part 1 primary objective: To evaluate the safety, tolerability
Slide 5: SUNFISH has a diverse patient population including patients with contractures, severe scoliosis and low baseline scores
SUNFISH has a diverse patient population including patients with contractures, severe scoliosis and low baseline motor function scores Part 2 Part 1 Total Patient baseline characteristics (N=51) Risdiplam Placebo* (N=180) (n=120) (n=60) Age at screening, years, median (range) 7 (2–24) 9 (2–25) 9 (2–
Slide 6: Change from baseline in MFM32 total score generally stable over 36 months
Following an initial increase over 12 months the change from baseline in MFM32 total score was generally stable over 36 months Overall population 2–25 years old Overall population 2–25 years old 80 change from baseline in MFM32 3 Percentage of patients with 70 Mean change from baseline 2 60 in MFM32
Slide 7: Increase in RULM total score sustained up to Month 48 with risdiplam
The increase in RULM total score from baseline over 24 months was sustained up to Month 48 with risdiplam treatment Overall population 2–25 years old 4 Mean change from baseline in 3 RULM total score* 2 1 Risdiplam† (Months 0–48) Placebo‡ (Months 0–12) 0 -1 0 6 12 18 24 30 36 42 48 Visit (months) Ri
Slide 8: HFMSE total score change with risdiplam contrasts with natural history decline
Change from baseline in HFMSE total score with risdiplam treatment over 48 months in SUNFISH contrasts with an overall decline in a natural history cohort SUNFISH Part 2 Subset of PNCR population1 4 Overall population 2–25 years old 4 meeting key inclusion criteria of SUNFISH Part 2* 2–25 years old
Slide 9: SMAIS-ULM total score stabilization or improvement over 48 months
Patients and caregivers reported stabilization or continuous improvements in the SMAIS-ULM total score change from baseline with risdiplam treatment over 48 months Patient (≥12 years old) Caregiver (for all patients) 4 4 baseline in SMAIS-ULM 3 3 Mean change from baseline in SMAIS-ULM Mean change fr
Slide 10: Observed AE profile over 48 months reflective of underlying disease
SUNFISH Parts 1 and 2: the observed AE profile over 48 months was reflective of underlying disease Number of AEs per Number of AEs per SUNFISH Part 1 (N=51) 100PY SUNFISH Part 2 (N=179)* 100PY (95% CI) (95% CI) Total PY at risk 247.4 Total PY at risk 662.5 Headache 59.8 (50.6–70.3) Headache 39.9 (35
Slide 11: Overall rate of AEs and SAEs per 100PY
SUNFISH Parts 1 and 2: overall rate of AEs and SAEs per 100PY SUNFISH Part 1 SUNFISH Part 2 900 40 800 35 700 30 SAEs per 100PY† AEs per 100PY† 600 25 500 20 400 15 300 200 10 100 5 0 0 0 to ≤12 >12 to ≤24 >24 to ≤36 >36 to ≤48 0 to ≤12 >12 to ≤24 >24 to ≤36 >36 to ≤48 Time on treatment (months) Tim
Slide 12: Treatment adherence was high in SUNFISH Parts 1 and 2
Treatment adherence was high in SUNFISH Parts 1 and 2 Part 1 Part 2* 99.4 98.7 (80.0–100.0) (34.7–127.4) Adherence/dose intensity†, mean % (95% CI) Adherence/dose intensity†, mean % (95% CI) Proportion of patients with adherence/dose 98 Proportion of patients with adherence/dose 98.3 intensity† ≥80%
Slide 13: Conclusions
Conclusions Increases in motor Patients and caregivers AEs and SAEs were function scores observed reported continuous reflective of in the first year of improvement or underlying disease. risdiplam treatment stabilization in the level The overall rate of were sustained of help needed for AEs decreas
Slide 14: Acknowledgments
Acknowledgments Many thanks to all the patients who participate in these studies, their families, healthcare professionals and the support of patient groups throughout the world 14
Slide 15: 8% of patients discontinued from SUNFISH Part 2 over 48 months
A total of 8% (14/180) of patients discontinued from SUNFISH Part 2 over 48 months Patients enrolled (N=180) Risdiplam Placebo* (n=120) (n=60) Withdrawn due to starting Withdrawn due to Risdiplam Placebo 0 to ≤12 months another treatment† starting another (n=117) (n=3) (n=59) treatment (n=1)‡ Withdr
Slide 16: SUNFISH Part 1 MFM32 increases maintained between Months 12 and 48
In SUNFISH Part 1, increases in MFM32 total score from baseline were maintained between Months 12 and 48 in patients treated with risdiplam Mean change from baseline 5 in MFM32 total score* 4 3 Risdiplam, SUNFISH Part 1† 2 1 0 -1 0 12 24 36 48 Visit (months) Patients (n)‡ 44 44 44 43 43 43 41 36 38
Slide 17: Key demographic variables in SUNFISH Part 2 and the PNCR Network population
Key demographic variables in SUNFISH Part 2 and the PNCR Network population SUNFISH Part 2 PNCR1 (risdiplam arm) n=91* n=120 Gender, female/male, n (%) 51/49 42/58 Ethnicity, Asian/white/black or African American, % 19/67/2 11/68/0 Age at enrollment/screening, years, median (IQR) 9 (5–14) 8 (4–14) A