Genentech/Roche Small Molecule
Risdiplam is an investigational SMN2 splicing modifier that is given daily by mouth or by g-tube as a liquid and distributes widely throughout the body. Risdiplam has been designed to help the SMN2 gene produce more SMN protein, as people with SMA have a reduced level of SMN protein. Risdiplam is being developed by Genentech/Roche, in collaboration with PTC Therapeutics and the SMA Foundation. Risdiplam was previously known as RG7916.
Ongoing Clinical Trials
What is FIREFISH?
FIREFISH is a two-part study in babies aged 1 to 7 months with Type 1 SMA. It is an open label study, which means that all babies receive risdiplam and there is no placebo. The objective of Part 1 was to assess the safety and concentration of risdiplam in plasma at several different dose levels.
Next steps for FIREFISH
Part 1 has been completed. Information from Part 1 has allowed us to confirm the dose of risdiplam to be investigated in Part 2, which will assess the safety and effiacy of risdiplam. Participants of Part 1 are receiving risdiplam and are still enrolled in FIREFISH as part of an open-label extension phase.
Part 2 is underway and will assess the safety and efficacy of risdiplam, including an additional 40 babies between the ages of 1 and 7 months. The main analysis of efficacy and safety of risdiplam will occur after all babies have completed one year of treatment, and efficacy will be determined by the number of babies that can sit without assistance after one year of treatment.
What is SUNFISH?
SUNFISH is a two-part study evaluating risdiplam in people with Type 2 and 3 SMA between 2 and 25 years of age. The objective of Part 1 was to assess the safety profile and concentration of risdiplam at several different dose levels as well as the level of SMN protein in blood in this population. Participants were randomized so that 2 out of every 3 people receive risdiplam and one receives placebo.
Next steps for SUNFISH
Information from Part 1 has allowed us to confirm the dose of risdiplam to be investigated in Part 2. Part 2 will assess the efficacy and safety of risdiplam. Enrollment into Part 2 of SUNFISH is almost complete, and approximately 168 participants will be included. The main analysis of the efficacy and safety of risdiplam will take place after all participants receive one year of treatment.
What is JEWELFISH?
JEWELFISH is an exploratory study investigating the safety of risdiplam in people who have Type 2 or 3 SMA, are between 12 and 60 years old and who have previously taken part in a clinical study with another SMN2 targeting therapy.
Next steps for JEWELFISH
The JEWELFISH study is currently ongoing in people aged 12 to 60 years who have previously received an SMN2 targeting therapy as part of a clinical study. We are in conversations with Health Authorities to broaden the inclusion criteria and increase the number of participants in JEWELFISH to include those who:
- received nusinersen as part of their regular medical care for SMA
- have SMA Type I
- are 6 months of age or older.
Further plans for JEWELFISH include eligibility for people who are still actively taking part in the OLEOS study (olesoxime long term safety and effiacacy study). These updates to JEWELFISH will be made subject to approval by Health Authorities and Ethics Committees.
Upcoming Clinical Trials
The RAINBOWFISH study will evaluate risdiplam in pre-symptomatic babies. More details on this study will be available in the coming months.
Resources and Further Information
- July 2018 Community Update on Risdiplam
- Roche SMA Trials
- Roche Releases Community Statement on RG7916 and Olesoxime Programs
- Genentech/Roche to Present New RG7916 Data at the 2018 American Academy of Neurology (AAN) Annual Meeting
- Genentech/Roche Releases Clinical Trial Update for RG7916
- Genentech/Roche Releases Clinical Trial Update for SUNFISH (RG7916)
- Roche Announces New Clinical Trial of RG7916
- Preliminary Data from FIREFISH Trial in Type 1 SMA Infants Presented at the International Scientific Congress on SMA
Data and Study Results
- Genentech Announces New Data for Risdiplam in Spinal Muscular Atrophy (SMA) at the World Muscle Society Congress
- RG7916 Significantly Increases SMN Protein in SMA Type 1 Babies
- Updated pharmacodynamic and safety data from SUNFISH Part 1, a study evaluating the oral SMN2 splicing modifier RG7916 in patients with Type 2 or 3 spinal muscular atrophy
- A long-term, open-label follow-up study of Olesoxime in patients with Type 2 or non-ambulatory Type 3 spinal muscular atrophy who participated in a placebo-controlled phase 2 trial
- Preliminary evidence for pharmacodynamic effects of RG7916 in JEWELFISH
- Relationship between central and peripheral SMN protein increase upon treatment with RG7916 (RO7034067)