Roche’s spinal muscular atrophy (SMA) drug Evrysdi (risdiplam) has helped pre-symptomatic babies reach rare milestones after two years of treatment in a Phase II trial.
The Rainbowfish trial (NCT03779334), run by the Roche subsidiary Genentech, enrolled babies aged from birth to six weeks who had not yet shown symptoms of SMA. After two years, all 26 children were able to swallow and feed orally, and none required permanent ventilation. This is a significant contrast to untreated Type 1 SMA, where children would typically not reach these milestones and rarely survive past two years old, according to natural history studies.
The cognitive development of the children was also comparable to babies without SMA, as measured by the Bayley Scales of Infant and Toddler Development, third edition (BSID-III). According to Genentech, this is the first clinical trial in SMA to evaluate cognitive skills as an exploratory endpoint using a standardised scale.
The data was presented at the World Muscle Society (WMS) Congress 2024, in Prague, Czech Republic, from 8 to 12 October.
This builds on previously announced one-year data, where the trial met its primary endpoint with 80% of patients sitting without support for at least five seconds after one year of Evrysdi treatment, measured by BSID-III. Of the 26 babies, 81% could sit independently for 30 seconds. Adverse events (AEs) for the drug included teething, Covid-19, fever, eczema, and constipation.
SMA is a genetic disorder characterised by the loss of motor neurons, leading to muscle weakness and progressive physical disability. It is caused by mutations in the SMN1 gene, resulting in a deficiency of SMN protein, which is critical for muscle function.
Evrysdi is an oral survival motor neuron 2 (SMN2) splicing modifier that targets mutations in chromosome 5q, which is implicated in survival motor neuron (SMN) protein deficiency. It was approved by the US Food and Drug Administration (FDA) in 2022 to treat SMA in patients of all ages, including infants under two months with Type 1, Type 2, or Type 3 SMA, or those with one to four SMN2 copies.
Genentech’s chief medical officer Levi Garraway highlighted the potential of Evrysdi in combination with newborn screening programmes: “These two-year findings confirm the potential of early intervention with Evrysdi to meaningfully improve the lives of children with SMA. Working in tandem with newborn screening programs, Evrysdi is the only non-invasive SMA treatment that can be administered during a child’s first hours of life.”
Evrysdi generated CHF 1.4bn ($1.64bn) in 2023 for Genentech, as per the company’s annual report, with projections from GlobalData estimating $2.8bn in revenue by 2030. Evrysdi’s main competitor, Biogen’s Spinraza (nusinersen) won FDA approval in 2016 for infants, children, and adults with SMA. Spinraza is projected to generate less than Evrysdi in 2030, at $1.13bn, mainly due to the favourable oral delivery of Evrysdi compared to the intrathecal route (via a lumbar puncture) for Spinraza.
GlobalData is the parent company of Pharmaceutical Technology.
In addition to SMN-targeting treatments like Evrysdi and Spinraza, Novartis’ gene therapy Zolgensma (onasemnogene abeparvovec) can also be administered to infants with SMA. Zolgensma delivers a new, working copy of a human SMN gene which is administered in a one-time infusion to children under two years of age. Despite its effectiveness, some infants may be unable to access the gene therapy due to its invasive nature, cost, and accessibility.
Evrysdi is also being evaluated in other clinical trials, including the Phase II Jewelfish trial (NCT03032172) in people with SMA aged six months to 60 years who received other investigational or approved SMA therapies for at least 90 days prior to receiving Evrysdi.
