Genentech's Evrysdi aids babies with SMA in achieving rare milestones during Phase II trial

Roche's spinal muscular atrophy (SMA) medication, Evrysdi (risdiplam), has demonstrated significant progress in pre-symptomatic infants over a two-year period according to findings from a Phase II clinical trial. The Rainbowfish study, overseen by Roche's subsidiary Genentech, involved infants from birth to six weeks old who had not yet exhibited SMA symptoms. After two years of Evrysdi treatment, all 26 participating children could swallow and feed orally without the need for permanent ventilation. This is a stark improvement compared to the typical outcomes for untreated Type 1 SMA, where children often do not reach these developmental milestones and rarely survive beyond two years, based on historical data.

The cognitive development of the infants treated with Evrysdi was comparable to that of their peers without SMA, as determined by the Bayley Scales of Infant and Toddler Development, third edition (BSID-III). This trial marks the first instance where an SMA clinical study has assessed cognitive abilities as an exploratory endpoint using a standardized scale. These findings were presented at the World Muscle Society (WMS) Congress 2024, held in Prague, Czech Republic, from October 8 to 12.

The new data builds on previously reported one-year results from the trial, which met its primary endpoint. After one year of treatment with Evrysdi, 80% of the infants could sit without support for at least five seconds, as measured by the BSID-III. Additionally, 81% of the 26 infants were able to sit independently for 30 seconds. Reported adverse events included teething, Covid-19, fever, eczema, and constipation.

Spinal muscular atrophy is a genetic disorder characterized by the loss of motor neurons, leading to progressive muscle weakness and physical disability. It is caused by mutations in the SMN1 gene, resulting in a shortage of the survival motor neuron (SMN) protein, which is essential for muscle function. Evrysdi is an oral medication that modifies the splicing of the SMN2 gene to increase SMN protein production. The drug received approval from the U.S. Food and Drug Administration (FDA) in 2022 for treating SMA in patients of all ages, including infants younger than two months with Type 1, Type 2, or Type 3 SMA, or those with one to four copies of the SMN2 gene.

Levi Garraway, Genentech's chief medical officer, emphasized the potential benefits of Evrysdi when used in conjunction with newborn screening programs. He noted, "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."

In 2023, Evrysdi generated CHF 1.4 billion ($1.64 billion) for Genentech, with projections from GlobalData estimating revenue of $2.8 billion by 2030. Evrysdi's primary competitor, Biogen's Spinraza (nusinersen), received FDA approval in 2016 for treating SMA in infants, children, and adults. Spinraza is projected to generate less revenue than Evrysdi by 2030, primarily due to the convenience of Evrysdi's oral administration compared to Spinraza's intrathecal delivery method.

In addition to SMN-targeting treatments like Evrysdi and Spinraza, Novartis offers a gene therapy called Zolgensma (onasemnogene abeparvovec) for SMA. Zolgensma introduces a functional copy of the SMN gene through a one-time infusion for children under two years old. However, the accessibility of Zolgensma can be limited due to its invasive nature, cost, and availability.

Evrysdi is also being tested in other clinical trials, such as the Phase II Jewelfish trial (NCT03032172), which includes participants with SMA aged six months to 60 years who have previously received other investigational or approved SMA treatments for at least 90 days before starting Evrysdi.