▎WuXiEdited by Kant Content Team

Recently, Genentech, a subsidiary of Roche, announced the latest long-term data from the pivotal FIREFISH study of its drug Evrysdi (risdiplam). The analysis showed that by the end of the fifth year, 91% of children with Type 1 Spinal Muscular Atrophy (SMA) treated with Evrysdi were still alive.Natural history studies show that, without treatment, children with Type 1 SMA struggle to reach such milestones and typically do not survive beyond the age of 2.

FIREFISH is an open-label pivotal study consisting of two parts, with a median age of infants at enrollment being 5.5 months. Of the 58 infants who completed the first year of treatment, 52 entered the open-label extension study. Analysis showed that the trial met its primary endpoint. By the end of the fifth year,91% of children with Type 1 SMA treated with Evrysdi survived, and 81% survived without permanent ventilation.59%Children can maintain a sitting position without support for at least 30 seconds.By the end of the fifth year, seven children were able to stand, three needed support, four required no assistance, and six could walk with support.

According to the motor scale assessment of the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) and the Hammersmith Infant Neurological Examination-2 (HINE-2), the motor abilities of children treated with Evrysdi were maintained or continued to improve. The FIREFISH results showed,Most children receiving Evrysdi treatment also maintained their ability to eat and swallow. Among the children assessed in the 5th year, 96% were able to swallow, and 80% could eat without a feeding tube.

Moreover, no treatment-related adverse events (AEs) leading to treatment discontinuation or study withdrawal were observed. The overall incidence of AEs decreased by 66% from the first year to the last year of the study. The most common AEs were upper respiratory tract infection (64%), fever (64%), and pneumonia (50%). During the 5-year treatment period, hospitalization rates declined, and since starting Evrysdi treatment, 22% of children did not require any hospitalization at all.

▲EvrysdiBy adjustingSMN2 RNA Splicing Enhances SMN Protein Levels (Image Source:PTC Therapeutics Official Website)

SMA is a severe, progressive, and potentially fatal neuromuscular disease. It affects approximately one in ten thousand infants and is the leading genetic cause of infant mortality. SMA is caused bySMN1Caused by a gene mutation that leads to the deficiency of the survival motor neuron (SMN) protein. This protein is present throughout the body and is crucial for the function of controlling muscles and motor neurons. Although SMA mainly occurs during infancy, patients may be of any age range from infants to adults.

Evrysdi is a targetedSMN2Small molecule mRNA splicing modulator developed jointly by Genentech and PTC Therapeutics. Carried in the human body.SMN2Although the gene can also express SMN protein, due to mRNA splicing errors, the level of normal SMN protein expression is very low and cannot compensate.SMN1SMN protein deficiency caused by gene mutation.Evrysdi modulates throughSMN2Splicing of gene mRNA to increase the level of mRNA capable of expressing normal SMN protein, thereby alleviating symptoms in SMA patients.Evrysdi is a liquid formulation medication that can be taken orally at home or administered through a feeding tube in liquid form. According to the press release,Evrysdi is the first oral, non-invasive small molecule drug for SMA treatment., which can be systematically delivered to the central nervous system (CNS) and peripheral tissues.