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 Part I tested the drug’s biological activity and safety in two different dosing regimens. Part II, which is now ongoing, measures the compound’s efficacy at the optimal dose selected in Part I. As of January 2019, Firefish is ongoing in Belgium, Brazil, China, France, Germany, Italy, Japan, Poland, Russia, Spain, Switzerland, Turkey and the United States, however recruitment has now closed 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 closed in July 2018; 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 January 2019, this trial is gradually taking off across Europe and planned to start in the UK.
- Rainbowfish – a clinical trial for babies younger than 6 weeks who have been diagnosed with SMA but do not yet show any symptoms. All babies will receive risdiplam for 24 months and then invited to take part in a 3-year extension trial. As of April 2019, the trial is active in Gdansk, Poland while sites in Australia, Belgium, Brasil, Italy, Russia and USA are awaiting activation.