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Genentech, a member of the Roche Group, today presented 1-year data from the pivotal Part 2 of the SUNFISH study, evaluating risdiplam in people aged 2-25 years with Type 2 or Type 3 spinal muscular atrophy (SMA). The study showed that change from baseline in the primary endpoint of the Motor Function Measure 32 scale (MFM-32)1 was significantly greater in people treated with risdiplam, compared to placebo (1.55 point mean difference; p=0.0156). The Revised Upper Limb Module (RULM),2 a key secondary endpoint, also showed an improvement (1.59 point difference; p=0.0028). Safety for risdiplam in the SUNFISH study was consistent with its known safety profile. Data were presented at the 2nd International Scientific and Clinical Congress on Spinal Muscular Atrophy from February 5-7, 2020, in Evry, France.

As anticipated, exploratory subgroup analyses showed that the strongest responses in MFM-32 versus placebo were observed in the youngest age group (2-5 years) (78.1% vs. 52.9% achieving ≥3 point increase). Importantly, disease stabilization was observed in the 18-25 years age group (57.1% vs. 37.5%, with stabilization defined as a ≥0 point increase), which is the goal of treatment for those with more established disease.

About the SUNFISH Study

SUNFISH is a two-part, double-blind, placebo-controlled pivotal study in people aged 2-25 years with Type 2 or Type 3 SMA. Part 1 (n=51) determined the dose for the confirmatory Part 2. Part 2 (n=180) evaluated motor function using total score of Motor Function Measure 32 (MFM-32) at 12 months.

About risdiplam

Risdiplam is an investigational, oral medicine that is systemically distributed and designed to increase SMN protein levels in the central nervous system (CNS) and throughout the body. It is designed to help the SMN2 gene produce more functional SMN protein, to better support motor neurons and muscle function. Roche and Genentech are leading the clinical development of risdiplam in collaboration with the SMA Foundation and PTC Therapeutics. In November 2019, the U.S. Food and Drug Administration (FDA) granted Priority Review for risdiplam with an expected decision on approval by May 24, 2020. Risdiplam is currently being evaluated in four multicenter trials in people with SMA:

  • SUNFISH (NCT02908685) – as outlined above. 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 and the first two secondary endpoints. The total change from baseline in Hammersmith Functional Motor Scale Expanded (HFMSE) was numerically greater for risdiplam but did not reach significance relative to placebo.
  • 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. The primary objective of Part 1 was to assess the safety profile of risdiplam in infants and determine the dose for Part 2. Part 2 is a pivotal, single-arm study of risdiplam in 41 infants with Type 1 SMA treated for 24 months, followed by an open-label extension. Enrollment for Part 2 was completed in November 2018. The primary objective of Part 2 is to assess efficacy as measured by the proportion of infants sitting without support after 12 months of treatment, as assessed in 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).
  • JEWELFISH (NCT03032172) – an open-label exploratory trial in people with SMA Type 1, 2 or 3 aged 6 months to 60 years who have been previously treated with SMA therapy, gene therapy or olesoxime. The study has completed recruitment.
  • 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 6 weeks of age (at first dose) with genetically diagnosed SMA who are not yet presenting with symptoms. The study is currently recruiting.

Roche/Genentech have opened an expanded access program (EAP) in the U.S. in order to provide access to risdiplam for eligible patients, pending potential commercial availability in the United States. For inquiries regarding the risdiplam EAP, please consult with your healthcare provider. Additional information can be found by calling the Genentech Trial Information Support Line at (888) 662-6728 (Monday-Friday, 5 a.m.-5 p.m. PST).

 

1. MFM-32 is a validated scale used to evaluate fine and gross motor function in people with neurological disorders, including SMA. It assesses 32 different motor functions from standing and walking to the use of hands and fingers.

2. RULM is a scale designed to assess upper limb movement in people with SMA. It can capture progressive muscle weakness across the spectrum of the disease, reflective of the SUNFISH Part 2 study population.