Risdiplam (or Evrysdi®) obtained marketing authorization in the United States last August for patients with SMA from 2 months old. Under review by the European regulatory authorities, it is still evaluated by several clinical trials conducted in type II or III SMA (NCT02908685), type I SMA (NCT02913482), in patients aged 6 months to 60 years old and who have previously received other treatment for SMA (NCT03032172 ) and in pre-symptomatic infants less than 6 weeks old (RAINBOWFISH trial).
Retinal toxicity reported in monkeys …
Preclinical studies published in 2018 and carried out in the macaque, with several doses of risdiplam had demonstrated retinal toxicity after 5 to 6 months of treatment. This toxicity resulted in degeneration of the macula as well as peripheral photoreceptors. In both cases, the monkeys were given higher doses than the dose used in humans. According to the authors, risdiplam has a strong capacity to bind to melanin, which could explain its retention in the cells of the retinal pigment. This retinal toxicity nevertheless appears specific to monkeys.
.. but not in human
Ophthalmologic follow-up was performed every 2 to 6 months in 245 people receiving risdiplam in the SUNFISH, FIREFISH and JEWELFISH trials. No abnormalities of the retina, either functional or structural, have been reported, including in younger patients with normal retinal maturation.
Ophthalmologic monitoring would not be necessary for patients, children and adults, receiving risdiplam at the therapeutic dose.
