Clinical Trials

Overview

Risdiplam (Evrysdi™) – Roche

Risdiplam was developed in collaboration with Roche, the SMA Foundation and PTC Therapeutics. Marketed as Evrisdy™, it is the third disease-modifying treatment available in Europe for 5q SMA.

Risdiplam is an oral small molecule, designed to increase the amount of SMN protein made by the SMN2 gene. Risdiplam is distributed throughout the body, raising the levels of SMN protein in various organs, not just the central nervous system.

About Evrysdi™

Method of Action

Like nusinersen, risdiplam is a selective SMN2 gene splicing modifier. It works by controlling the SMN2 gene splicing by promoting the inclusion of exon 7, leading to the production of a functional SMN protein.

View Method of Action

Trials of risdiplam (RO7034067)

Trial Name
MANATEE
Age:
Part 1: 2-10 years; Part 2: 2-25 years
Aim:
This trial will study the safety and efficacy of RO7204239 in combination with risdiplam in patients with spinal muscular atrophy (SMA). The trial has two parts; Part 1 is the dose-finding part in SMA patients that are either ambulant (aged 2-10 years) or non-ambulant (aged 5-10 years) within separate cohorts, and Part 2 is the pivotal part in SMA patients aged 2-25 years that are ambulant.
Status:
Part 1 - Active, not recruiting; Part 2: not yet recruiting 
Locations:
Australia, Belgium, Canada, Croatia, Italy, Japan, Netherlands, Poland, Portugal, Spain, UK, USA
Identifier:
NCT05115110
Trial Name
RAINBOWFISH
Age:
Up to 6 weeks old
Aim:
To investigate the efficacy, safety, pharmacokinetics, and pharmacodynamics of risdiplam in infants aged from birth to 6 weeks who have been genetically diagnosed with SMA but are not yet presenting with symptoms
Status:
Active, not recruiting
Locations:
Belgium, Italy, Poland, Russian Federation, Australia, Brazil, China, Saudi Arabia, Taiwan & USA
Identifier:
NCT03779334
Trial Name
JEWELFISH
Age:
6 Months to 60 Years old
Aim:
To investigate the safety, tolerability, PK, and PK/PD relationship of risdiplam in adults, children and infants with SMA previously enrolled in Study BP29420 (Moonfish) with the splicing modifier RO6885247 or previously treated with nusinersen, olesoxime or AVXS-101.
Status:
Active, not recruiting
Locations:
Belgium, France, Germany, Italy, the Netherlands, Poland, Switzerland, UK & USA
Identifier:
NCT03032172
Trial Name
SUNFISH
Age:
2 to 25 Years old
Aim:
To investigate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of Risdiplam in Type 2 and 3 SMA patients
Status:
Complete
Locations:
Belgium, Croatia, France, Italy, Poland, Russian Federation, Serbia, Spain, Switzerland, Turkey, Ukraine, Brazil, Canada, China, Japan, Saudi Arabia and USA
Identifier:
NCT02908685
Trial Name
FIREFISH
Age:
Type 1 SMA – 1 to 7 Months old
Aim:
To investigate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of risdiplam in infants with Type 1 SMA
Status:
Complete
Locations:
Belgium, Croatia, France, Germany, Italy, Poland, Russian Federation, Serbia, Spain, Turkey, UK, Brazil, China, Japan and USA
Identifier:
NCT02913482
Trial Name
PUPFISH
Age:
<20 days at first dose
Aim:
This study will evaluate the pharmacokinetics (PK) and safety of risdiplam in participants with spinal muscular atrophy (SMA) under 20 days of age at first dose.
Status:
Recruiting
Locations:
Belgium, Canada, Germany, Italy, Norway, Poland, US
Identifier:
NCT05808764
Trial Name
HINALEA 1
Age:
< 2 years of age
Aim:
This study will evaluate the effectiveness and safety of risdiplam administered as an early intervention in paediatric patients with spinal muscular atrophy after gene therapy
Status:
Recruiting
Locations:
Poland, US (more sites to be added in coming months)
Identifier:
NCT05861986
Trial Name
HINALEA 2
Age:
< 2 years of age
Aim:
This study will evaluate the effectiveness and safety of risdiplam administered as in paediatric patients with spinal muscular atrophy who experienced a plateau or decline in function after gene therapy
Status:
Recruiting
Locations:
Poland, US (more sites to be added in coming months)
Identifier:
NCT05861999

Community updates

Regulatory

  • March 2024 - Findings on the risdiplam tablet formulation and next steps. Read it here.
  • July 2023 - CHMP positive opinion recommending the approval of an extension of the indication for risdiplam (Evrysdi) to include all ages, including infants with SMA from birth. Read it here.
  • February 2021 - EMA’s CHMP gives positive opinion for approval of Evrysdi™ (risdiplam) for the treatment of 5q SMA
  • August 2020 - EMA has validated the Marketing Authorisation Application (MAA) for risdiplam for the proposed use in people living with SMA
  • August 2020 - Risdiplam approved for the treatment of SMA in the US
  • April 2020 - Update on the clinical development of risdiplam, regulatory filings in certain countries
  • January 2020 - Roche announces global pre-approval access/ compassionate use (PAA/CU) plans for risdiplam
  • November 2019 - FDA grants priority review to risdiplam for the treatment of SMA & Roche’s letter to the community

MANATEE

  • October 2021 - Roche to start MANATEE, a global combination study in early 2022

FISH TRIALS

  • October 2023 - Update on the results from the primary analysis: RAINBOWFISH clinical trial.
  • May 2022 - FDA (U.S. Food and Drug Administration) approves a label expansion for risdiplam
  • April 2022 - Three year data from Roche's Evrysdi (risdiplam) shows long-term improvement in Babies with Type 1 SMA
  • March 2022 - New data for Roche's Evrysdi (risdiplam) demonstrate long-term efficacy and safety in a broad population of people with SMA
  • July 2021 - Data for Evrysdi® published in New England Journal of Medicine shows significant improvement in survival and motor milestones in babies with Type 1 SMA (Firefish)
  • June 2021 - Evrysdi improves motor function in pre-symptomatic babies after one year and its safety profile in previously treated people with SMA is confirmed (Jewelfish & Rainbowfish)
  • March 2021 - update on longterm data from part 2 of the SUNFISH trial
  • December 2020 - Summary of work carried out in 2020 together with lay summaries on FIREFISH & SUNFISH
  • September 2020 - Update on part 1 of the FIREFISH clinical trial
  • June 2020 - Roche presents new data on SUNFISH & JEWELFISH trials at the Cure SMA Annual 2020 virtual Conference
  • April 2020 - Update on the clinical development of risdiplam (Sunfish)
  • February 2020 - Roche completes recruitment for JEWELFISH clinical trial
  • February 2020 - Risdiplam shown to improve motor function in people aged 2 to 25 with type 2 or 3 SMA (sunfish)
  • January 2020 - Risdiplam’s FIREFISH meets primary endpoint in trial in infants with type 1 SMA
  • November 2019 - Roche’s risdiplam meets primary endpoint in pivotal SUNFISH trial in people with type 2 or 3 SMA
  • May 2019 - Update on FIREFISH & SUNFISH presented at the 2019 AAN conference
  • October 2018 - Update of FIREFISH & SUNFISH studies of risdiplam
  • March 2018 - Start of pivotal part of FIREFISH for babies with Type 1 SMA
  • October 2017 - Interim results of Part 1 of the SUNFISH study indicate RG7916 is well tolerated at all doses. The first patient has now been enrolled for Part 2.
  • September 2017 - Start of Part 2 of the SUNFISH study. Enrolment is expected to begin in September 2017 in France and Belgium. Italy, Switzerland, Germany and Spain will begin later in the year.

MOONFISH

  • August 2017 - Eye toxicity finding in RG7800 and its relationship with RG7916.

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