SMA Treatment Risdiplam Demonstrates Continued Improvements in FIREFISH Study


The ability to feed orally and swallow was maintained by an overwhelming number of patients treated with risdiplam at 24 months.

Levi Garraway, MD, PhD

Levi Garraway, MD, PhD

Newly announced 2-year data from part 2 of the FIREFISH study (NCT02913482) of risdiplam (Evrysdi; PTC Therapeutics) in infants with type 1 spinal muscular atrophy (SMA) demonstrated that the treatment continued to improve motor function between months 12 and 24, including the ability to sit without support.1

Results also showed that risdiplam continued to improve survival as well as the ability to feed orally, and reduced the need for permanent ventilation. These longer-term data build upon 1-year pivotal findings from FIREFISH part 2 that will be presented at the upcoming 2021 American Academy of Neurology (AAN) Annual Meeting, April 17-22.

The primary end point, percentage of infants able to sit without support for at least 5 seconds at month 12, was met by 29% (12 of 41) of participants at 12 months and improved to 61% (25 of 41) by month 24. Furthermore, continued improvements in the ability to sit without support for at least 30 seconds were shown at month 24 indicated by 44% (18 of 41) of infants compared to 17% (7 of 41) at 12 months. Researchers used Gross Motor Scale of the Bayley Scales of Infant and Toddler Development Edition 3 (BSID-III) to assess this patient population.

At month 24, 92% (35 of 38) of infants treated with risdiplam maintained the ability to feed orally, contrary to the natural course of the disease where infants with type 1 SMA older than 12 months generally require feeding support. Additionally, exploratory data also showed that 95% (36 of 38) of patients gained the ability to swallow.

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"These data highlight the real-world impact of this transformative medicine in babies with the most severe form of SMA,” Levi Garraway, MD, PhD, chief medical officer, and head, Global Product Development, Roche, said in a statement. “These results increase our understanding of how this first-of-its-kind treatment can extend the lives of babies with type 1 SMA, providing much needed hope for their families.”

After 24 months of treatment, 93% (38 of 41) of infants were alive and 83% (34 of 41) were alive and free from permanent ventilation, an improvement compared to the natural course of the disease. Researchers recorded no deaths between months 12 and 24. Compared to the natural course of the disease, there were fewer hospitalizations during the second year of treatment with risdiplam, with 34% of infants (14 of 41) not requiring hospitalization.

The adverse events (AEs) and serious AEs were consistent with what had been previously observed in other risdiplam studies. All told, upper respiratory tract infection (54%), pneumonia (46%), pyrexia (44%), constipation (29%), nasopharyngitis (17%), bronchitis (15%), diarrhea (15%), and rhinitis (12%) were the most common AEs.

Between the first and second 12-month periods of FIREFISH part 2, the incidence of serious pneumonia declined by approximately 3-fold. Pneumonia (39%) and respiratory distress (7%) were the most common serious AEs observed. Notably, there were no drug-related AEs leading to withdrawal or treatment discontinuation.

"The natural course of type 1 SMA shows us that, sadly, without treatment children are never able to sit without support and typically don’t survive beyond the age of 2,” FIREFISH investigator Basil Darras, MD, professor of neurology, Harvard Medical School, and director, Spinal Muscular Atrophy Program, Boston Children’s Hospital, said in a statement. “Infants treated with Evrysdi also experienced a range of improvements in motor function abilities, a reduction in serious events typically caused by disease progression, such as the need for permanent ventilation or hospitalization, and increased rate of survival.”

Results from part 1 of the FIREFISH study of risdiplam published in March showed that in the 0.2 mg/kg daily high-dose cohort B (n = 17), 88% of infants were event-free after 24 months. Additionally, 59% (n = 10) of those infants were able to sit without support for at least 5 seconds, as measured by the BSID-III scores at 24 months, an improvement from 41% (n = 7) at 12 months. All 7 of the infants achieving that milestone at 12 months maintained it by 24 months.2

Risdiplam received FDA approval for the treatment of SMA in adults and children 2 months of age and older in August 2020. To date, the drug has been approved in 39 countries and submitted in a further 33 countries.1

1. Genentech’s Evrysdi continues to improve motor function and survival in babies with type 1 spinal muscular atrophy (SMA). News release. Genentech. April 15, 2021. Accessed April 15, 2021.
2. Darras BR, Baranello G, Boespflug-Tanguy O, et al. FIREFISH Part 1: 24-month safety and exploratory outcomes of risdiplam in infants with Type 1 spinal muscular atrophy (SMA). Presented at: MDA Clinical and Scientific Conference 2021; March 15-18.
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