Risdiplam (RG7916, RO7034067) is an oral drug being developed as a treatment for SMA by Roche, PTC Pharmaceuticals, and SMA Foundation. The molecule modifies alternative splicing of the SMN2 gene in such a way that the gene starts producing only the SMN protein, which is deficient in all those with SMA.
Risdiplam is a successor to RG7800, an earlier molecule that was trialled in patients in a study called Moonfish but whose development was stopped in 2015 after unexpected toxicity was observed in laboratory animals (but not in humans).
Risdiplam was tested for safety in healthy adult volunteers in early 2016. In October 2016, a phase 2/3 clinical trial started, this time involving actual SMA patients. As of now, the compound’s properties are being tested in three trials:
- Firefish – a clinical trial that will enroll at least 48 babies diagnosed with SMA type 1 aged 1–7 months. This is a 24-month open-label trial where everyone will receive the active substance. The trial consists of two parts. The ongoing Part I tests the drug’s biological activity and safety in two different dosing regimens. Part II, which is yet to start, will primarily measure the compound’s efficacy at the optimal dose. As of September 2018, Firefish Part I is ongoing in Belgium, Brazil, China, France, Germany, Italy, Japan, Poland, Russia, Spain, Switzerland, Turkey and the United States but recruitment is now closing and no new babies can be enrolled.
- Sunfish – a clinical trial that enrolls children and young adults aged 2–25 who have SMA type 2 or 3 and are unable to walk unsupported. Like Firefish, this trial consists of two parts: Part I, which aimed at establishing the optimal dose, and Part II, which is verifying the molecule’s efficacy. Unlike Firefish, Sunfish is a controlled trial in which 67% participants receive the active substance and 33% receive placebo for some time (for 12 months in Part II) before being switched to the active substance for the remainder of the 24-month study. Recruitment for Sunfish has closed; no UK hospital is participating.
- Jewelfish – a clinical trial for participants aged 12–60 who have a history of receiving RG7800 or olseoxime experimentally or who were treated with nusinersen (provided they will discontinue it). As of early 2018, this trial is not open for recruitment anywhere in Europe, although this may change in the coming months.
- Rainbowfish – a planned clinical trial for babies who have been diagnosed prenatally with SMA but do not yet show any symptoms. The trial is planned to be opened across the world. We do not yet know whether UK is on the list.