Evrysdi found safe, effective for SMA types 1-3 in new analysis

Approved therapy seen to stabilize or improve motor function

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Note: This article was updated Sept. 25 to clarify that respiratory declines were observed in patients with SMA types 2 and 3 and that the type of blood clots observed in Evrysdi-treated patients were deep vein thromboses.

Evrysdi (risdiplam) safely stabilizes or improves motor function for most people with spinal muscular atrophy (SMA) types 1, 2, or 3, according to a new meta-analysis that reviewed more than a half-dozen studies of the approved therapy.

The findings related to respiratory function were less consistent, however, with data indicating that patients with SMA types 2 and 3 still tended to see respiratory declines while on treatment.

“[Evrysdi] is an effective and safe treatment for all three types of SMA,” the scientists wrote, adding, “Although adverse events were common, they were rarely serious and/or required dose modification or discontinuation of the drug.”

The researchers noted that more work is needed to understand how Evrysdi and other SMA therapies, such as Spinraza (nusinersen) and Zolgensma (onasemnogene abeparvovec), could be used together in the clinic.

The study, “Efficacy of risdiplam in spinal muscular atrophy: A systematic review and meta-analysis,” was published in the journal Pharmacotherapy.

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Evrysdi for SMA now approved in Europe for use in all ages

Researchers examine Evrysdi outcomes using 7 published studies

A daily medication that can be given at home, Evrysdi works to increase levels of the SMN protein that is lacking in the most common types of SMA. Its U.S. approval in 2020 made it the third approved SMN-targeted therapy for SMA and the first that could be taken orally.

It is indicated in the U.S. and in Europe for people of any age and with any type of SMA.

A range of clinical trials and real-world studies have demonstrated the potential benefits of Evrysdi in SMA, including stabilizations or improvements in motor function and preserved respiratory function.

Now, scientists conducted a systematic review of previously published studies related to the safety and efficacy of Evrysdi. Their review overall included 11 studies involving 641 patients, and focused on individuals with either SMA type 1 — the most common form of the disorder — or types 2/3.

Across all the studies, Evrysdi generally was associated with motor improvements or stabilizations, with gains particularly observed in presymptomatic SMA babies, but its effects on respiratory function were not as clear. Common side effects included gastrointestinal issues, skin disorders, elevations in liver enzymes, and a type of blood clot called deep vein thrombosis.

A meta-analysis, a statistical approach used to analyze results of multiple studies at once, was then performed using data from seven eligible studies.

The results indicated that, following a year of treatment, more than half (57%) of children with SMA type 1 achieved a score of at least 40 points on the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), a commonly used assessment in SMA. With a maximum score of 64 indicating normal motor abilities, babies with SMA type 1 don’t usually reach a score of 40 if left untreated.

Moreover, 85% could feed orally, 53% had head control, and 32% could sit up for more than five seconds — milestones that generally were maintained for at least two years.

“This improvement represents a dramatic change from historical cohorts [patient groups] where these motor milestones and motor function are rarely achieved,” the researchers wrote.

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Findings not consistent on respiratory function among patients

Among those with SMA types 2 or 3, motor stabilizations or improvements also were observed, as assessed by the 32-item Motor Function Measure (MFM32), Revised Upper Limb Module (RULM), and the Hammersmith Functional Motor Scale – Expanded (HFMSE).

Evrysdi was associated with a 2.09-point improvement in MFM32 and a 1.73-point improvement in RULM after a year relative to the start of treatment. These scores were maintained or further improved after two years. A significant, 1-point elevation in HFMSE scores also were observed after a year.

However, efficacy in terms of respiratory function were not consistent in these patients, with key measures indicating respiratory declines in some while others remained stable.

Overall, 16% of participants experienced adverse events after one year and 19% after two years, but there were too few reports of serious side effects for a statistical analysis.

This [meta-analysis of Evrysdi studies] shows an improvement in the lives of these people beyond the improvement in clinical parameters.


Although not included in the analysis, the researchers also noted that several studies showed gains in patient-reported outcomes relative to fatigue, cognition, strength, dexterity, speech, well-being, and life quality.

“This shows an improvement in the lives of these people beyond the improvement in clinical parameters,” the scientists wrote.

While the findings back the clinical benefits of Evrysdi, the researchers emphasized that they do not allow for a direct comparison to Spinraza or Zolgensma.

Still, Evrysdi could offer some benefits to patients given those therapies, according to the team, particularly because of its oral route of administration.

The scientists believe future work should explore whether Evrysdi is helpful as a maintenance therapy for people treated with Zolgensma or Spinraza, or for patients who don’t completely respond to them.

As with previous studies, the findings also indicated that responses to treatment are “likely to be greater in presymptomatic or early stage patients, although this is a hypothesis that needs to be confirmed in future studies,” the team concluded.