Dalia Moawad, MD, Executive Director, Head of Neurological Rare Diseases, Medical Affairs at Genentech, outlines the company’s Evrysdi (risdiplam) clinical development program. This program was designed to represent a broad spectrum of people living with spinal muscular atrophy (SMA). 

Spinal muscular atrophy (SMA) is a rare inherited neuromuscular disorder caused by an inadequate level of the survivor motor neuron (SMN) protein due to mutations in the SMN1 gene. The absence of the SMN protein leads to cellular imbalances in motor neurons that in turn causes the motor neuron endplates to not properly connect to muscle and the motor neurons die.

As Dr. Moawad explains, there are currently 4 clinical trials within this program which together account for SMA patients of various ages with varying experience with previous treatment and who have different forms of SMA.

FIREFISH is a phase 2/3, 2-part, multicenter, open-label trial of risdiplam in infants 2 to 7 months of age with infantile-onset SMA (SMA type 1). Part 1 of this study was designed to be a dose-finding study for risdiplam. The results of part 1 were recently published in the New England Journal of Medicine. In part 2 of the FIREFISH study, the primary endpoint is achievement of a motor milestone at 12 months, as measured by Item 22 of the BSID-III gross motor scale. Results from part 2 will be announced at the AAN 2021 Annual Meeting (April 17-22, 2021).

SUNFISH is a 2-part, double-blind, placebo controlled pivotal study in people aged 2-25 years with SMA Type 2 or 3. Part 1 determined the dose of risdiplam for the confirmatory Part 2. Part 2 evaluated motor function using total score of Motor Function Measure 32 (MFM-32) at 12 months. MFM-32 is a validated scale used to evaluate fine and gross motor function in people with neurological disorders, including SMA. The study met its primary endpoint.

JEWELFISH is an open-label exploratory trial designed to assess the safety, tolerability, pharmacokinetics and pharmacodynamics in people with SMA aged 6 months to 60 years who received other investigational or approved SMA therapies for at least 90 days prior to receiving Evrysdi. The study has completed recruitment.

RAINBOWFISH is an open-label, single-arm, multicenter study, investigating the efficacy, safety, pharmacokinetics and pharmacodynamics of Evrysdi in infants from birth to 6 weeks of age (at first dose) with genetically diagnosed SMA who are not yet presenting with symptoms. The study is currently recruiting.

To learn more about SMA, click here.