Evrysdi by Genentech and spinal muscular atrophy types 2 and 3 update

South San Francisco, CA March 20, 2023 Press release

Genentech’s new four-year data on Evrysdi confirms long-term efficacy and safety profile in some of the most severely affected people with spinal muscular atrophy (SMA) types 2 and 3
Data from the pivotal SUNFISH study showed that the increase in motor function observed during the first year was maintained through the fourth year, while the overall incidence of adverse events continued to decrease.

Evidence supports the long-term efficacy and safety profile of Evrysdi in a wide range of people with SMA type 2 and non-ambulatory type 3.

More than 8,500 people, from newborns to over 60s, have been treated with Evrysdi, which is approved in more than 90 countries.

SOUTH SAN FRANCISCO, CA – March 19, 2023

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced new long-term data on Evrysdi.^® (risdiplam) in a wide range of people aged 2 to 25 years with spinal muscular atrophy (SMA) in the pivotal SUNFISH study. The data confirm that the improvement in motor function was sustained over four years, and the overall incidence of adverse events continued to decrease over the 48-month period, enhancing Evrisdi’s long-term efficacy and safety. Participants also reported consistent improvement or stabilization when performing daily activities on their own, such as lifting and moving objects. The data were presented at the Muscular Dystrophy Association (MDA) Clinical and Scientific Conference, March 19-22, 2023.

“Maintaining long-term independence and the ability to perform daily tasks is an important measure for people living with SMA and those caring for them. It is heartening to see that Evrysdi has made a significant difference in this aspect of their lives,” said Laurent Servais, MD, Professor of Pediatric Neuromuscular Diseases at the Oxford Neuromuscular Center MDUK. “This trial involved people with SMA types 2 and 3, including patients with advanced disease. These latest data give us confidence that the improvement seen during the first year of treatment is maintained for four years, in contrast to the decline we would have seen without treatment.”

The increase in motor function from baseline observed during the first year of the study was maintained through the fourth year of treatment with Evrisdi, as measured by changes in Motor Function Measurement 32 (MFM-32) and in the Revised Upper Limb Module (RULM). Untreated natural history data indicate that patients with type 2 or 3 SMA typically experience a decrease in motor function over time. Evrisdi was well tolerated over a four-year period. Adverse events (AEs) and serious adverse events (SAEs) reflected the underlying disease. The most commonly reported AEs include headache, fever (fever), and upper respiratory infections. None of the treatment-related AEs resulted in withdrawal from the study.

“These new data show that treatment with Evrysdi may help people with type 2 or 3 SMA maintain improvements in muscle strength and mobility for several years,” said Levi Garraway, MD, Genentech’s chief medical officer and head of global product development. . “The long-term results of this study complement the robust findings of our broad program of clinical trials that evaluate Evrysdi in different age groups, disease severity, and treatment histories.”

In addition to bringing Evrysdi to people around the world, Genentech is also conducting clinical development in collaboration with the SMA Foundation and PTC Therapeutics. Genentech is currently investigating Evrysdi in combination with a muscle-growth antimyostatin molecule in a Phase II/III MANATEE study for the treatment of SMA.

About Evrisdi^® (risdiplam)
Evrysdi is a surviving motor neuron splicing modifier 2 (SMN2) developed for the treatment of SMA caused by mutations on chromosome 5q that result in a deficiency of the surviving motor neuron (SMN) protein. Evrysdi is administered daily at home in liquid form by mouth or through a tube.

Evrysdi is designed to treat SMA by increasing and maintaining SMN protein production in the central nervous system (CNS) and peripheral tissues, as demonstrated in animal models. The SMN protein is found throughout the body and is critical for maintaining healthy motor neurons and movement.

Evrysdi received PRIME status from the European Medicines Agency (EMA) in 2018 and orphan status from the US Food and Drug Administration in 2017. Drug Research Award for drug discovery. Evrysdi is currently approved in more than 90 countries, and a dossier is pending in 16 other countries.

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

• FIREFISH (NCT02913482) is a two-part, open-label pivotal clinical trial in infants with type 1 SMA. Part 1 was a dose escalation study in 21 infants with the primary objective of evaluating the safety profile of risdiplam in infants and determining the dose for Part 2. Part 2 is a pivotal one-arm study of risdiplam in 41 type 1 infants. SMA was treated for two years followed by an open extension. Enrollment in Part 2 was completed in November 2018. The primary goal of Part 2 was to assess effectiveness, measured by the proportion of infants sitting unsupported after 12 months of treatment, on the Bailey Infant and Infant Gross Motility Scale. Toddler Development – Third Edition (BSID-III) (defined as sitting without support for 5 seconds). The study reached its primary endpoint.
• SUNFISH (NCT02908685) is a double-blind, placebo-controlled, two-part pivotal study in people aged 2 to 25 years with type 2 or 3 SMA. Part 1 (n=51) determined the dose for confirmation part 2. Part 2 (n=180) assessed motor function using the total Motor Function Measure 32 (MFM-32) score at 12 months. The MFM-32 is a validated scale used to assess fine and gross motor skills in people with neurological disorders, including SMA. The study reached its primary endpoint.
• JEWELFISH (NCT03032172) is an open-label investigational study designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics in people with SMA aged 6 months to 60 years who received other investigational or approved drugs for the treatment of SMA for at least 90 days prior to admission Evrisdi drug. The study completed recruitment (n=174).
• RAINBOWFISH (NCT03779334) is an open-label, single-arm, multicenter study investigating the efficacy, safety, pharmacokinetics, and pharmacodynamics of risdiplam in children (~n=25) from birth to six weeks of age (at the first dose) with genetically diagnosed SMA who are not yet symptomatic . The study is fully credited.
• MANATEE (NCT05115110) is a phase II/III global clinical trial to evaluate the safety and efficacy of GYM329 (RG6237), an anti-myostatin molecule that targets muscle growth, in combination with Evrysdi for the treatment of SMA in patients aged 2-10 years. age. In December 2021, the FDA’s Office of Orphan Drug Development granted GYM329 orphan drug designation for the treatment of patients with SMA. The study is currently being recruited.

About SMA
SMA is a severe, progressive neuromuscular disease that can be fatal. It affects about one in 10,000 children and is the leading genetic cause of infant mortality. SMA is caused by a mutation in the survival motor neuron 1 (SMN1) gene, resulting in a deficiency of the SMN protein. This protein is found throughout the body and is essential for the functioning of the nerves that control muscles and movement. Without it, nerve cells cannot function properly, which eventually leads to muscle weakness. Depending on the type of SMA, a person’s physical strength and ability to walk, eat, or breathe can be greatly reduced or lost.

What is Evrisdi?
Evrysdi is a prescription drug used to treat spinal muscular atrophy (SMA) in children and adults.

Important safety information

• Before taking Evrysdi, tell your healthcare provider if you have any medical conditions, including if you:
  • are pregnant or planning to become pregnant, as Evrysdi may harm your unborn baby. Ask your health care provider for advice before taking this medicine.
  • a woman who can become pregnant:
    • Before you start treatment with Evrisdi, your doctor may test you for pregnancy.
    • Talk to your healthcare provider about birth control methods that may be right for you. Use contraceptives during treatment and for at least 1 month after you stop taking Evrisdi.
    • Register of pregnant women. If you become pregnant while taking Evrisdi, contact your doctor immediately. Ask about registration in the Evrysdi Pregnancy Registry, which was created to collect information about your health and the health of your baby. Your health care provider can add you to this registry by calling 1-833-760-1098 or away http://www.evrysdipregnancyregistry.com
  • are an adult male. Evrisdi can affect a man’s ability to have children (fertility). Ask your health care provider for advice before taking this medicine.
  • are breastfeeding or plan to breastfeed. It is not known if Evrisdi passes into breast milk and if it could harm your baby.
• Tell your doctor about all medicines you are taking
• You must get Evrysdi from a pharmacy in liquid form. If the medicine in the vial is a powder, don’t use it. Contact your pharmacist for a replacement
• Avoid getting Evrysdi on the skin or in the eyes. If Evrysdi gets on your skin, wash the area with soap and water. If Evrisdi gets into your eyes, rinse your eyes with water.
• The most common Evrysdi side effects include:
  • For late-onset SMA:
  • For SMA with infantile onset:
    • heat
    • diarrhea
    • rash
    • runny nose, sneezing, and sore throat (upper respiratory infection)
    • lung infection (lower respiratory tract infection)
    • constipation
    • vomit
    • cough

These are not all the possible side effects of Evrisdi. For more information about the risks and benefits of Evrysdi, ask your health care provider or pharmacist.

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

Please see in full Appointment Information for more important security information or visit http://www.evrysdi.com/.

About Genentech in Neuroscience
Neurology is Genentech’s main research and development focus. Our goal is to use cutting-edge science to develop new treatments that help improve the lives of people with chronic and potentially devastating illnesses.

Genentech and Roche are investigating more than a dozen drugs for neurological disorders, including multiple sclerosis, spinal muscular atrophy, neuromyelitis optica spectrum disorders, Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, and Duchenne muscular dystrophy. Together with our partners, we strive to push the boundaries of scientific understanding in order to solve some of the most challenging problems in modern neuroscience.

About Genentech
Founded over 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and markets drugs to treat patients with serious and life-threatening diseases. The company, part of the Roche group, is headquartered in South San Francisco, California. For more information about the company, please visit