- FIREFISH Part 1 data show treatment with Evrysdi at 12 months helped 90% of these infants survive without permanent ventilation and 33% sit without support, a key motor milestone not normally seen in the natural course of the disease
- The FDA approved Evrysdi in
August 2020 as the first and only at home SMA treatment with proven efficacy in adults, children and infants 2 months and older
“Since Evrysdi was FDA approved in August, we have been inspired by the stories and sense of hope that we have heard from people living with SMA and their families about the impact Evrysdi has had in their lives,” said
The exploratory efficacy analysis found that after 12 months of treatment, seven (33%; 7/21) infants were able to sit without support for at least 5 seconds, assessed by the Gross Motor Scale of the Bayley Scales of Infant and
In the low- and high-dose cohorts, no infant lost the ability to swallow over 12 months, and 86% (18/21) were able to feed orally, either exclusively or in combination with a feeding tube at 12 months. In addition, 90% (19/21) of infants were alive without permanent ventilation after 12 months of treatment with Evrysdi. Three infants experienced fatal complications of their disease after approximately one, eight and 13 months of treatment, respectively. An additional infant passed away after the data cut-off with death occurring approximately 3.5 months after receiving the last dose of study drug. None of these have been attributed by the investigator as related to Evrysdi.
The researchers also assessed motor function with the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), a scale used for infants with Type 1 SMA. Results showed that 11 out of the 21 infants (52%) had a CHOP-INTEND total score of 40 points or higher. The CHOP-INTEND scale ranges from 0 to 64, with higher scores indicating better function.
The most common adverse events included fever (pyrexia; 52%), upper respiratory tract infections (43%), diarrhea (29%), cough (24%), vomiting (24%), constipation (19%) and pneumonia (19%). In total, 24 serious adverse events were reported as of the clinical data cut-off, with the most common including pneumonia in three infants and respiratory tract infection, viral respiratory tract infection, acute respiratory failure and respiratory distress in two infants each.
Among the 21 infants enrolled in Part 1 of the FIREFISH study, the median duration of treatment was 14.8 months at the time of analysis. The median age at enrollment was 6.7 months and symptom onset between the ages of 28 days to 3 months.
In
FIREFISH, an open-label, two-part pivotal study, was designed to assess Evrysdi safety, tolerability, efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) in patients aged 1 to 7 months with Type 1 SMA. Part 1 evaluated several doses of Evrysdi and determined the therapeutic dose of 0.2 mg/kg for Part 2.
Evrysdi has been and continues to be studied in more than 450 people as part of a large and robust clinical trial program in SMA.
About Evrysdi™ (risdiplam)
Evrysdi is a survival of motor neuron 2 (SMN2) splicing modifier designed to treat SMA by increasing production of the survival of motor neuron (SMN) protein. SMN protein is found throughout the body and is critical for maintaining healthy motor neurons and movement. Evrysdi is administered daily at home in liquid form by mouth or by feeding tube.
The
Evrysdi is currently being evaluated in four multicenter trials in people with SMA:
- FIREFISH (NCT02913482) – an open-label, two-part pivotal clinical trial in infants with Type 1 SMA. Part 1 was a dose-escalation study in 21 infants with the primary objective of assessing the safety profile of Evrysdi in infants and determining the dose for Part 2. Part 2 is a pivotal, single-arm study of Evrysdi in 41 infants with Type 1 SMA treated for 2 years, followed by an open-label extension. Enrollment for Part 2 was completed in
November 2018 . The primary objective of Part 2 was to assess efficacy as measured by the proportion of infants sitting without support after 12 months of treatment, as assessed in the Gross Motor Scale of the Bayley Scales of Infant andToddler Development – Third Edition (BSID-III) (defined as sitting without support for 5 seconds). The study met its primary endpoint. - SUNFISH (NCT02908685) – SUNFISH is a two-part, double-blind, placebo controlled pivotal study in people aged 2-25 years with Types 2 or 3 SMA. Part 1 (n=51) determined the dose for the confirmatory Part 2. Part 2 (n=180) evaluated motor function using total score of Motor Function Measure 32 (MFM-32) at 12 months. MFM-32 is a validated scale used to evaluate fine and gross motor function in people with neurological disorders, including SMA. The study met its primary endpoint.
- JEWELFISH (NCT03032172) – an open-label exploratory trial designed to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) in people with SMA aged 6 months to 60 years who received other investigational or approved SMA therapies for at least 90 days prior to receiving Evrysdi. The study has completed recruitment (n=174).
- RAINBOWFISH (NCT03779334) – an open-label, single-arm, multicenter study, investigating the efficacy, safety, pharmacokinetics and pharmacodynamics of Evrysdi in babies (~n=25), from birth to six weeks of age (at first dose) with genetically diagnosed SMA who are not yet presenting with symptoms. The study is currently recruiting.
About SMA
SMA is a severe, progressive neuromuscular disease that can be fatal. It affects approximately one in 10,000 babies and is the leading genetic cause of infant mortality. SMA is caused by a mutation of the survival motor neuron 1 (SMN1) gene, which leads to a deficiency of SMN protein. This protein is found throughout the body and is essential to the function of nerves that control muscles and movement. Without it, nerve cells cannot function correctly, leading to muscle weakness over time. Depending on the type of SMA, an individual’s physical strength and their ability to walk, eat or breathe can be significantly diminished or lost.
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