• Data from ongoing FIREFISH study confirm long-term efficacy and safety profile of Evrysdi in children with Type 1 SMA 
• Ninety-one percent of children were alive at month 48 
• More than 95% maintained the ability to swallow - without treatment they would have required feeding support and majority would have died within 2 years 
• Evrysdi is now approved in 99 countries with more than 8,500 patients treated globally 

SOUTH SAN FRANCISCO, Calif. / Jun 30, 2023 / Business Wire / Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today new long-term data for Evrysdi^® (risdiplam) from the open-label extension (n=50) of the pivotal FIREFISH study, reinforcing its sustained efficacy and safety profile in children with Type 1 spinal muscular atrophy (SMA). FIREFISH is a two-part study in babies aged 1-7 months at the time of enrollment. After four years of treatment with Evrysdi, many of the babies, now young children, continued to improve their ability to sit, stand and walk without support. All the Evrysdi-treated children who were alive at the time of the primary analysis were still alive at month 48.

Additionally, the majority of infants maintained their ability to feed by mouth and swallow up to month 48. Motor function was assessed by the Gross Motor Scale of the Bayley Scales of Infant and Toddler Development Third Edition (BSID-III) and Hammersmith Infant Neurological Examination 2 (HINE-2) and abilities were either maintained or improved over four years of Evrysdi treatment. Without treatment, children with Type 1 SMA are not expected to live past two years of age and are never able to sit without support. These data were presented at the Cure SMA Research & Clinical Care Meeting, June 28 – 30, 2023.

Among the infants treated with Evrysdi (n=58), 37 were able to sit without support for at least 5 seconds at month 48, compared to 35 at month 24 (BSID-III). In addition, 36 infants were able to sit without support for at least 30 seconds at month 48, up from 23 infants at month 24. Between month 24 and month 48, three infants gained the ability to stand alone and one infant gained the ability to walk alone.

“Evrysdi’s oral route of administration allows the medicine to be distributed throughout the body, systemically increasing SMN protein production, the lack of which is the underlying cause of SMA,” said Dr. Giovanni Baranello, UCL Great Ormond Street Institute of Child Health & Great Ormond Street Hospital, London, U.K. “This has shown to help in delivering a meaningful impact on important functions of daily living including motor milestones, feeding and swallowing, which were maintained or improved in this long-term study, while also offering a tolerable safety profile.”

Evrysdi is the first and only small molecule pre-mRNA splicing modifier that targets survival motor neuron-2 (SMN2) for the treatment of SMA, and can be administered at home in liquid form by mouth or by feeding tube.

“The independence that comes with sitting, standing and walking is transformational for children with SMA, and their families, and we are very encouraged by how these skills increased over four years of Evrysdi treatment for many children in this study,” said Levi Garraway, M.D., Ph.D., Genentech’s chief medical officer and head of Global Product Development. “Nine out of 10 patients in our studies remain on Evrysdi long-term and these data underscore its importance as an option for people with SMA across a broad range of age and disease types.”

No treatment-related adverse events (AEs) led to treatment discontinuation or withdrawal from the study, and the rate of AEs decreased by 71% between the first and fourth 12 month periods. The most common AEs were pyrexia (62%), upper respiratory tract infection (62%) and pneumonia (48%). The rate of hospitalizations decreased over the study period. Genentech leads the clinical development of Evrysdi as part of a collaboration with the SMA Foundation and PTC Therapeutics.

About Evrysdi^® (risdiplam)

Evrysdi is a survival motor neuron 2 (SMN2) splicing modifier designed to treat SMA caused by mutations in chromosome 5q that lead to survival motor neuron (SMN) 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 (CNS) and peripheral tissues as demonstrated in animal models. SMN protein is found throughout the body and is critical for maintaining healthy motor neurons and other functions such as swallowing, speaking, breathing and movement.

Evrysdi was granted PRIME designation by the European Medicines Agency (EMA) in 2018 and Orphan Drug Designation by the U.S. 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 99 countries and the dossier is under review in a further 18 countries.

Evrysdi is currently being evaluated in five multicenter trials in people with SMA:

• FIREFISH (NCT02913482) – an open-label, two-part pivotal clinical trial in infants with Type 1 SMA. The study met its primary endpoint.
• SUNFISH (NCT02908685) – a two-part, double-blind, placebo-controlled pivotal study in people aged 2-25 years with Types 2 or 3 SMA. The study met its primary endpoint.
• JEWELFISH (NCT03032172) – an open-label exploratory trial designed to assess the safety, tolerability, pharmacokinetics and pharmacodynamics 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 fully enrolled.
• MANATEE (NCT05115110) – a global Phase II/III clinical study to evaluate the safety and efficacy of GYM329 (RG6237), an anti-myostatin molecule targeting muscle growth, in combination with Evrysdi for the treatment of SMA in patients 2-10 years of age. The FDA Office of Orphan Products Development granted GYM329 Orphan Drug Designation for the treatment of patients with SMA in December 2021. The study is currently recruiting.

About SMA

Spinal Muscular Atrophy (SMA) is a severe, progressive neuromuscular disease that can be fatal. It affects approximately one in 10,000 babies and is among the leading genetic causes 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 other functions such as swallowing, speaking, breathing 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, speak or breathe can be significantly diminished or lost.

What is Evrysdi?

Evrysdi is a prescription medicine used to treat spinal muscular atrophy (SMA) in children and adults.

Important Safety Information

• Before taking Evrysdi, tell your healthcare provider about all of your medical conditions, including if you:
  • are pregnant or plan to become pregnant, as Evrysdi may harm your unborn baby. Ask your healthcare provider for advice before taking this medicine
  • are a woman who can become pregnant:
    • Before you start your treatment with Evrysdi, your healthcare provider may test you for pregnancy
    • Talk to your healthcare provider about birth control methods that may be right for you. Use birth control while on treatment and for at least 1 month after stopping Evrysdi
    • Pregnancy Registry. There is a pregnancy registry for women who take EVRYSDI during pregnancy. The purpose of this registry is to collect information about the health of the pregnant woman and her baby. If you are pregnant or become pregnant while receiving EVRYSDI, tell your healthcare provider right away. Talk to your healthcare provider about registering with the EVRYSDI pregnancy Registry. Your healthcare provider can enroll you in this registry or you can enroll by calling 1-833-760-1098 or visiting https://www.evrysdipregnancyregistry.com.
  • are an adult male. Evrysdi may affect a man's ability to have children (fertility). Ask a healthcare provider for advice before taking this medicine
  • are breastfeeding or plan to breastfeed. It is not known if Evrysdi passes into breast milk and may harm your baby
• Tell your healthcare provider about all the medicines you take
• You should receive Evrysdi from the pharmacy as a liquid. If the medicine in the bottle is a powder, do not use it. Contact your pharmacist for a replacement
• Avoid getting Evrysdi on your skin or in your eyes. If Evrysdi gets on your skin, wash the area with soap and water. If Evrysdi gets in your eyes, rinse your eyes with water
• The most common side effects of Evrysdi include:
  • For later-onset SMA:
    • fever
    • diarrhea
    • rash
  • For infantile-onset SMA:
    • fever
    • diarrhea
    • rash
    • runny nose, sneezing and sore throat (upper respiratory infection)
    • lung infection (lower respiratory infection)
    • constipation
    • vomiting
    • cough

These are not all of the possible side effects of Evrysdi. For more information on the risk and benefits profile of Evrysdi, ask your healthcare provider or pharmacist.

You may report side effects to the FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch. You may also report side effects to Genentech at 1-888-835-2555.

Please see full Prescribing Information for additional Important Safety Information or visit http://www.evrysdi.com/.

About Genentech in Neuroscience

Neuroscience is a major focus of research and development at Genentech. 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, spinal muscular atrophy, neuromyelitis optica spectrum disorder, Alzheimer’s disease, Huntington’s disease, Parkinson’s disease and Duchenne muscular dystrophy. 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.

About Genentech

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.