Therapy Areas: Respiratory
New Three-Year Data for Genentech's Evrysdi Show Long-Term Improvements in Survival and Motor Milestones in Babies with Type 1 Spinal Muscular Atrophy
29 April 2022 - - US-based biotechnology company Genentech, a member of Switzerland's Roche Group (SIX: RO) (OTCQX: RHHBY) has posted new three-year data from the FIREFISH study, including one-year data from the open label extension, reinforcing the long-term efficacy and safety of Evrysdi (risdiplam) in infants with symptomatic Type 1 spinal muscular atrophy, the company said.

The data showed an estimated 91% of infants treated with Evrysdi were alive after three years of treatment.

The Evrysdi-treated infants continued to improve or maintain motor functions, including the ability to swallow, sit without support, stand with support and walk while holding on, between two and three years of treatment.

Without treatment, children with Type 1 SMA are never able to sit without support. The study also showed overall continued reductions in serious adverse events and hospitalizations over time.

The FIREFISH study evaluated the efficacy and safety of Evrysdi in infants aged 1-7 months at the time of enrollment with Type 1 SMA.

The study was in two parts, with Part 1 being the dose-finding period and Part 2 evaluating the efficacy and safety at the dose selected in Part 1. The pooled population includes participants treated with Evrysdi at the approved dose for a minimum of three years.

These long-term data will be presented at the 14th European Paediatric Neurology Society Congress, April 28 May 2, 2022.

Infants treated with Evrysdi maintained or continued to improve in their ability to sit without support between 24-36 months.

Among the infants with an available assessment treated with Evrysdi, 32 infants maintained and four gained the ability to sit without support for at least five seconds since month 24, as assessed by the Gross Motor Scale of the Bayley Scales of Infant and Toddler Development Third Edition (BSID-III).

In addition, 20 infants maintained and 15 gained the ability to sit without support for at least 30 seconds.

No infant who gained the ability to sit without support lost this ability after three years of treatment.

The majority of infants treated with Evrysdi maintained the ability to feed orally and swallow up to month 36.

Most of the infants treated with Evrysdi continued to improve or maintain measures of the Hammersmith Infant Neurological Examination 2 (HINE-2) between 24-36 months, including being able to hold their heads upright (36 maintained, 3 gained and none lost the ability since month 24), pivot while sitting (15 maintained, 11 gained and none lost the ability), stand with support (6 maintained, 5 gained and 1 lost the ability) and walk while holding on (1 maintained, 2 gained and none lost the ability).

The most common adverse events were pyrexia, upper respiratory tract infection, pneumonia, constipation, nasopharyngitis, diarrhea, rhinitis, vomiting and cough.

The most common SAEs were pneumonia, respiratory distress, viral pneumonia, acute respiratory failure and respiratory failure.

The rate of AEs, including pneumonia, continued to decrease over time.

The rate of SAEs similarly decreased, with a reduction of approximately 50% after each 12-month treatment period and a 78% reduction between the first and third year of treatment.

All AEs and SAEs reported were reflective of the underlying disease and there were no treatment-related AEs leading to withdrawal or treatment discontinuation.

The rate of hospitalizations decreased from 1.24 hospitalizations per patient year over 12 months to 0.70 hospitalizations over 36 months.

No additional deaths have occurred since the primary analysis of FIREFISH, up to the data cut-off of this analysis (November 23, 2021).

Genentech leads the clinical development of Evrysdi as part of a collaboration with the SMA Foundation and PTC Therapeutics.

Evrysdi is a survival motor neuron 2 splicing modifier designed to treat SMA caused by mutations in chromosome 5q that lead to survival motor neuron protein deficiency. Evrysdi is administered daily at home in liquid form by mouth or by feeding tube.

Evrysdi is designed to treat SMA by increasing and sustaining the production of SMN protein in the central nervous system and peripheral tissues as demonstrated in animal models.

SMN protein is found throughout the body and is critical for maintaining healthy motor neurons and movement.

Evrysdi was granted PRIME designation by the European Medicines Agency in 2018 and Orphan Drug Designation by the US Food and Drug Administration in 2017.

In 2021 Evrysdi was awarded Drug Discovery of the Year by the British Pharmacological Society as well as the Society for Medicines Research award for Drug Discovery.

Evrysdi is currently approved in 76 countries and the dossier is under review in a further 29 countries.