FIREFISH Trial Shows Risdiplam Benefits in Infants With Type 1 Spinal Muscular Atrophy - Neurology Advisor

Among infants with type 1 spinal muscular atrophy (SMA), treatment with risdiplam was associated with improvements in motor function and meeting developmental motor milestones, according to study results published in The New England Journal of Medicine.

Children with SMA may not be able to sit without support, walk, or hold their heads up, possibly because of variations in their survival of motor neuron (SMN) genes SMN1 and SMN2, resulting in reduced production of the functional SMN protein. Risdiplam, an orally administered small-molecule that increases the expression of SMN2 messenger RNA and levels of SMN protein, was approved for the treatment of patients with SMA aged 2 months and older.

The objective of the current trial (FIREFISH; ClinicalTrials.gov Identifier: NCT02913482) was to determine the efficacy and safety of risdiplam in infants with type 1 SMA aged between 1 and 7 months at enrollment.

Continue Reading

The open-label study included 41 infants (median age, 5.3 months; 22 girls) who received treatment at 14 centers in 10 countries. All participants had genetic and clinical diagnosis of type 1 SMA with 2 copies of SMN2.

The primary study outcome was the ability to sit without support for at least 5 seconds after 12 months of treatment. Key secondary endpoints were better motor function, defined as a score of 40 or higher on the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), an increase of 4 or more points from baseline in the CHOP-INTEND score, a motor-milestone response as measured by section 2 of the Hammersmith Infant Neurological Examination-2, and survival without permanent ventilation.

After 12 months of treatment with risdiplam, 12 of the 41 infants (29%) were able to sit without support for 5 or more seconds; this rate was significantly higher than the performance criterion rate of 5% from natural history data (P <.001).

Compared with those in the historical cohorts, infants who received treatment with risdiplam showed an improvement in motor function; 56% had a CHOP-INTEND score of 40 or greater, a significantly higher percentage than the performance criterion rate of 17% in the historical cohorts (P <.001). An increase of 4 or more points from baseline was also more common among patients who received risdiplam treatment compared with the historical cohorts (90% vs 17%, respectively; P <.001).

Motor milestone response, according to Hammersmith Infant Neurological Examination-2, was reported in 78% of patients who received risdiplam treatment for 12 months compared with 12% of those in the historical cohorts (P <.001).

Survival without permanent ventilation was also higher among patients who received risdiplam treatment compared with those in the historical cohorts (85% vs 42%, respectively; P <.001).

Overall, 254 adverse events were reported, 48 of which were serious. Serious adverse events included pneumonia (32%), bronchiolitis (5%), hypotonia (5%), and respiratory failure (5%). Fatal respiratory complications were reported in 3 infants.

The study had several potential limitations, including the small sample size of the historical cohorts and the use of historical control participants, which did not allow for comparisons to be made to study outcomes with the same confidence as comparisons in a randomized trial. Another study limitation was the open-label design.

"Oral risdiplam treatment over a period of 12 months in patients with type 1 SMA resulted in higher percentages of infants who met motor milestones, survived without need for ventilation, and showed improvements in motor function than the percentages in natural-history cohorts," the researchers concluded.

Disclosure: This research was supported by F. Hoffmann-La Roche. Please see the original reference for a full list of disclosures.

Reference

Darras BT, Masson R, Mazurkiewicz-Bełdzińska M, et al, for the FIREFISH Working Group. Risdiplam-treated infants with type 1 spinal muscular atrophy versus historical controls. N Engl J Med. 2021;385(5):427-435. doi:10.1056/NEJMoa2102047

Topics:

Neuromuscular Disorders Pediatric Neurology Pediatrics Spinal Muscular Atrophy

Adblock test (Why?)

Comments

Post a Comment

Popular posts from this blog

This fish is worth $300,000 - New York Post

This fish is worth $300,000 - New York Post This fish is worth $300,000 - New York Post Posted: 05 Jun 2016 12:00 AM PDT With exacting precision, the surgeon inserted the scalpel above the eyeball and cut out a snotty deposit of fatty tissue. The routine eye-lift was nearly complete when suddenly the patient awoke, suffocating, and began to flop about on the table. The audience gasped. Knowing time was of the essence, the surgeon scooped up the patient in his arms, raced across the stage, and dropped her into a tank of water. She revived. Because she was a fish. Yes, fish eye-lifts exist. As do fin jobs and tail tucks. The operating theater was a mall in Jakarta, Indonesia, where a pet expo was under way. As for the patient, she survived, her formerly droopy eyes now bright and perky. A good thing, too, as this was no ordinary goldfish but rather an Asian arowana, the world's most expensive aquarium denizen, rumored to sell for as mu
Read more

Catching Dory: selling aquarium fish supports coastal livelihoods in Indonesia | npj Ocean Sustainability - Nature.com

Image
Abstract The global marine aquarium trade has created new local markets across the planet, including in Indonesia, now the second-largest exporting country of marine aquarium fish in the world. Participating in the global aquarium trade has been touted as a potentially sustainable addition to fisher livelihoods, but scant data exist showing the numbers of fish coming off the reef and how those fish contribute to income. To determine how participants in the trade incorporate aquarium species in their livelihoods, we examine source-level aquarium fish collecting and trading data in the Banggai Archipelago, a region in Central Sulawesi that has become a significant source for popular aquarium, also known as ornamental, fish species. Using a sustainable livelihoods lens, we examine this data to understand how participants in the aquarium trade both contribute to as well as benefit from the trade and consider how their participation relates to emerging Blue Justice principles. From one year
Read more

NilocG Launches New Website for the Only All-in-One Thrive Fertilization Solution for Planted Aquariums - PRNewswire

Image
NilocG Launches New Website for the Only All-in-One Thrive Fertilization Solution for Planted Aquariums - PRNewswire NilocG Launches New Website for the Only All-in-One Thrive Fertilization Solution for Planted Aquariums - PRNewswire Posted: 11 Mar 2021 02:00 AM PST ALBANY, Ore. , March 11, 2021 /PRNewswire/ -- NilocG launches a new website for planted tank enthusiasts to gather and make THRIVE, a plant fertilizer that assures planted tank aquascapes flourish while eliminating the need for multiple products more readily available online. The company also takes it a step further in the industry, making its flagship product easy to dose, super-concentrated, and an all-in-one solution based on an effective EL dosing method with all essential micro and macronutrients. Continue Reading Thrive fertilizer: North America's most trusted aquarium plant fertilizer Colin Grice , CEO, a self-described planted tank lover, re
Read more