Wednesday, Feb 24, 2021
South San Francisco, CA -- February 24, 2021 --
Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that Evrysdi™ (risdiplam) data from the dose finding Part 1 of the pivotal FIREFISH study in infants with symptomatic Type 1 spinal muscular atrophy (SMA) were published in the February 24, 2021 online issue of the New England Journal of Medicine (NEJM). The data show that treatment with Evrysdi at 12 months helped 90% (19/21) of these infants survive without permanent ventilation and 33% (7/21) sit without support for at least 5 seconds, which is not normally seen in the natural course of the disease. The study also found that treatment with Evrysdi increased the levels of survival of motor neuron (SMN) protein by a median 1.9-fold from baseline in the high-dose cohort at 12 months.
“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 Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “The publication of the data in the New England Journal of Medicine reinforces the value of Evrysdi as an important treatment option for SMA.”
The exploratory efficacy analysis found that after 12 months of treatment, 7 (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 Toddler Development – Third Edition (BSID-III). All 7 infants who achieved this milestone received the high dose (41%; 7/17), which was the dose selected for the confirmatory Part 2 of the study. Nine of the infants in the high-dose cohort (53%; 9/17) had upright head control after 12 months of treatment, and 1 infant (6%; 1/17) was able to stand (bearing weight), as assessed by the Hammersmith Infant Neurological Examination Module 2 (HINE-2).
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 1, 8 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 3 infants and respiratory tract infection, viral respiratory tract infection, acute respiratory failure and respiratory distress in 2 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 September 2020, two-year results from FIREFISH Part 1 were presented and the exploratory efficacy data showed 88% of infants treated with Evrysdi were alive and did not require permanent ventilation at two years, and 59% of infants were able to sit without support for at least 5 seconds.
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 U.S. Food and Drug Administration (FDA) approved Evrysdi for the treatment of SMA in adults and children 2 months of age and older. Evrysdi was granted PRIME designation by the European Medicines Agency (EMA) in 2018 and Orphan Drug Designation by FDA and EMA in 2017 and 2019, respectively. At this time, Evrysdi has been approved in seven countries and submitted in 57, including the EU 27 and Norway and Iceland..
Evrysdi is currently being evaluated in four multicenter trials in people with 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.
What is Evrysdi?
Evrysdi is a prescription medicine used to treat spinal muscular atrophy (SMA) in adults and children 2 months of age and older.
It is not known if Evrysdi is safe and effective in children under 2 months of age.
Important Safety Information
These are not all of the possible side effects of Evrysdi. For more information on the risk and benefits profile of Evrysdi, patients should ask their healthcare provider or pharmacist.
Patients may report side effects to the FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch. Patients may also report side effects to Genentech at 1-888-835-2555.
Please see the full Prescribing Information for additional Important Safety Information.
About Genentech in Neuroscience
Neuroscience is a major focus of research and development at Genentech and Roche. Our goal is to pursue groundbreaking science to develop new treatments that help improve the lives of people with chronic and potentially devastating diseases.
Genentech and Roche are investigating more than a dozen medicines for neurological disorders, including multiple sclerosis, neuromyelitis optica spectrum disorder, Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, Duchenne muscular dystrophy and autism spectrum disorder. Together with our partners, we are committed to pushing the boundaries of scientific understanding to solve some of the most difficult challenges in neuroscience today.
Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com .
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