Babies’ Motor Function Improves After 2 Years on Evrysdi

Marisa Wexler MS avatar

by Marisa Wexler MS |

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After two years of treatment with Evrysdi (risdiplam), most babies with spinal muscular atrophy (SMA) type 1 in the FIREFISH clinical trial are still alive without a need for permanent ventilation, and many of the youngsters are showing continual improvements in motor development.

The results were published in The Lancet Neurology in the study “Safety and efficacy of risdiplam in patients with type 1 spinal muscular atrophy (FIREFISH part 2): secondary analyses from an open-label trial.” The work was funded by Roche, which markets Evrysdi through its subsidiary Genentech.

“These findings show meaningful gains in motor function beyond month 12, confirming that longer-term treatment with [Evrysdi] benefited patients with type 1 spinal muscular atrophy,” the researchers wrote.

Evrysdi is an oral treatment that works to boost production of the SMN protein, deficits of which cause SMA. It is approved to treat SMA patients of all ages in the U.S.

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The two-part Phase 2/3 FIREFISH trial (NCT02913482) is testing Evrysdi in babies with SMA type 1. After the first part of the trial identified an optimum dosage, the second part of FIREFISH enrolled 41 babies ages 1 to 7 months, all of whom were treated with Evrysdi.

Results at one year showed the trial met its main goal; most of the infants were alive and able to swallow, without a need for permanent ventilation.

After two years in the study, all 38 children who were alive at one year are still alive. One of these children has progressed to needing permanent ventilation, although the total number of participants requiring any form of respiratory support decreased from 10 (24%) at one year to eight (20%) at two years.

At one year, 34 of the children were able to feed by mouth; at two years, this number increased to 35.

The number of children able to sit unsupported for at least five seconds increased from 12 (29%) at one year to 25 (61%) at two years. Nearly half (44%) of the children could sit unsupported for at least 30 seconds by year two, as compared to 17% after one year.

“By month 24, 13 more infants were able to sit without support for at least 5 [seconds] and 11 more infants were able to sit without support for at least 30 [seconds],” the researchers wrote, adding, “Without treatment, children with type 1 spinal muscular atrophy are never able to sit without support, and thus the ability to achieve sitting is an important motor milestone in treated type 1 spinal muscular atrophy.”

None of the children were able to stand or walk independently at two years, though two were reported to be able to crawl on their hands and knees.


The proportion of patients reaching a score of at least 40 on the CHOP-INTEND, a standardized measure of motor development, increased from 56% after one year to 76% at two years.

“These findings show clinically meaningful gains in motor function and indicate a clear deviation from natural history data, where achievement of major motor milestones and a CHOP-INTEND score of 40 points or greater is rarely observed,” the researchers wrote.

Side effects related to Evrysdi were reported in seven (17%) of the children; these included rashes, skin discoloration, constipation, and altered levels of liver enzymes and blood cells. None of these events led to treatment discontinuation.

“The safety profile seen at 12 months was maintained at 24 months,” Susan Iannaccone, MD, a neurologist at University of Texas Southwestern Medical Center Medical School who has served as a consultant for Genentech, wrote in a commentary accompanying the study.

Compared to Spinraza, Zolgensma

According to Iannaccone, the motor gains seen in this study are somewhat less impressive than have been reported for other SMA therapies, namely Spinraza (nusinersen) and Zolgensma (onasemnogene abeparvovec-xioi).

“Milestones were reached later and fewer patients attained walking ability compared with results from clinical trials of [Spinraza] and [Zolgensma],” Iannaccone wrote. But she said these differences “could be related to the age at which patients were enrolled” — compared to trials of other therapies, FIREFISH included babies who were older when they started treatment and therefore probably had more advanced disease initially.

Iannaccone also noted that the improvements in motor function seen in FIREFISH are similar to improvements seen in trials of Spinraza: “There is a cumulative effect over time—the more doses received, the better the motor outcome,” she wrote.

“Therefore, the two key principles of treating spinal muscular atrophy are (1) the earlier the better and (2) prolonged use of disease-modifying therapy is better,” Iannaccone concluded.

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