New four-year data for Evrysdi reinforce long-term efficacy and safety profile in some of the most severely affected people with types 2 and 3 spinal muscular atrophy .- Genentech/Roche

Data confirm increases in motor function were sustained at four years and the overall rate of adverse events continued to decrease over the 48-month period , reinforcing the long-term efficacy and safety of Evrysdi. Participants also reported continuous improvement or stabilization when independently performing activities of daily living such as picking up and moving objects. The data were presented at the Muscular Dystrophy Association (MDA) Clinical and Scientific Conference, March 19-22, 2023.

“Preserving long-term independence and the ability to perform daily tasks is an important measure for people living with SMA and their caregivers. It’s encouraging to see that Evrysdi has meaningfully affected this aspect of their lives,” said Laurent Servais, M.D., Ph.D., Professor of Paediatric Neuromuscular Diseases at the MDUK Oxford Neuromuscular Centre. “This trial included people with Type 2 and 3 SMA, including patients with advanced disease. These latest data make us confident that the improvement observed during the first year of treatment is sustained during four years which contrasts with the decline we would observe in the absence of treatment.”

The increase in motor function from baseline observed during the first year of the study was maintained through the fourth year of treatment with Evrysdi, as measured by changes in Motor Function Measure 32 (MFM-32) and Revised Upper Limb Module (RULM). Without treatment, natural history data show that patients with Type 2 or 3 SMA typically show a decline in motor function over time. Evrysdi was well tolerated over the four-year time period. Adverse events (AEs) and serious adverse events (SAEs) were reflective of the underlying disease. The most commonly reported AEs include headache, fever (pyrexia) and upper respiratory tract infection. No treatment-related AEs led to withdrawal from the study.

In addition to bringing Evrysdi to people around the world, Genentech also leads its clinical development as part of a collaboration with the SMA Foundation and PTC Therapeutics. Genentech is currently investigating Evrysdi in combination with an anti-myostatin molecule targeting muscle growth in the Phase II/III trial MANATEE for the treatment of SMA.

Evrysdi is currently being evaluated in five multicenter trials in people with SMA : i. FIREFISH (NCT02913482) – an open-label, two-part pivotal clinical trial in infants with Type 1 SMA. Part 1 was a dose-escalation study in 21 infants with the primary objective of assessing the safety profile of risdiplam in infants and determining the dose for Part 2. Part 2 is a pivotal, single-arm study of risdiplam in 41 infants with Type 1 SMA treated for two years, followed by an open-label extension. Enrollment for Part 2 was completed in November 2018. The primary objective of Part 2 was to assess efficacy as measured by the proportion of infants sitting without support after 12 months of treatment, as assessed by the Gross Motor Scale of the Bayley Scales of Infant and Toddler Development – Third Edition (BSID-III) (defined as sitting without support for 5 seconds). The study met its primary endpoint. ii SUNFISH (NCT02908685) – a two-part, double-blind, placebo-controlled pivotal study in people aged 2-25 years with Types 2 or 3 SMA. Part 1 (n=51) determined the dose for the confirmatory Part 2. Part 2 (n=180) evaluated motor function using the total score of Motor Function Measure 32 (MFM-32) at 12 months. MFM-32 is a validated scale used to evaluate fine and gross motor function in people with neurological disorders, including SMA. The study met its primary endpoint. iii. JEWELFISH (NCT03032172) – an open-label exploratory trial designed to assess the safety, tolerability, pharmacokinetics and pharmacodynamics in people with SMA aged 6 months to 60 years who received other investigational or approved SMA therapies for at least 90 days prior to receiving Evrysdi. The study has completed recruitment (n=174). iv.RAINBOWFISH (NCT03779334) – an open-label, single-arm, multicenter study, investigating the efficacy, safety, pharmacokinetics, and pharmacodynamics of risdiplam in babies (~n=25), from birth to six weeks of age (at first dose) with genetically diagnosed SMA who are not yet presenting with symptoms. The study is fully enrolled. v. MANATEE (NCT05115110) – a global Phase II/III clinical study to evaluate the safety and efficacy of GYM329 (RG6237), an anti-myostatin molecule targeting muscle growth, in combination with Evrysdi for the treatment of SMA in patients 2-10 years of age. The FDA Office of Orphan Products Development granted GYM329 Orphan Drug Designation for the treatment of patients with SMA in December 2021. The study is currently recruiting.