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Data for Genentech’s Evrysdi (risdiplam) Published in New England Journal of Medicine Shows Significant Improvement in Survival and Motor Milestones in Babies With Type 1 Spinal Muscular Atrophy (SMA)

July 28, 2021 Off By BusinessWire

– FIREFISH Part 2 study showed treatment with Evrysdi helped babies stay free of permanent ventilation, sit without support and improve across a range of motor milestones –

– Evrysdi has proven efficacy in adults, children and babies 2 months and older with over 4,000 patients treated to date –

– SMA is the leading genetic cause of death in infants –

SOUTH SAN FRANCISCO, Calif.–(BUSINESS WIRE)–Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that the New England Journal of Medicine (NEJM) has published data from FIREFISH Part 2, a pivotal global study evaluating the efficacy and safety of Evrysdi^® (risdiplam) in babies aged 1-7 months old with symptomatic Type 1 spinal muscular atrophy (SMA). The study met its primary endpoint with 29% of infants (12/41) sitting without support for at least 5 seconds* by month 12, a milestone not seen in the natural course of the disease. Safety for Evrysdi in the FIREFISH Part 2 study was consistent with its known safety profile.

“Without treatment, babies with Type 1 SMA are unlikely to survive beyond two years of age,” said Professor Laurent Servais, M.D., Ph.D., FIREFISH investigator and Professor of Pediatric Neuromuscular Diseases at the MDUK Oxford Neuromuscular Center. “Important motor milestones, such as sitting, rolling over and swallowing, are the fundamental building blocks that can help these babies achieve optimal outcomes with Evrysdi, potentially reducing the need for ventilation and increasing the rate of survival.”

At the time of the data analysis, the median duration of treatment with Evrysdi was 15.2 months and the median age was 20.7 months. At month 12, 93% (38/41) of infants were alive and 85% (35/41) were free from permanent ventilation. Without treatment, the median age of death or permanent ventilation was 13.5 months in a natural history cohort. Ninety percent (37/41) had a CHOP-INTEND** score increase of at least 4 points, with 56% (23/41) achieving a score above 40; the median increase was 20 points.

In addition, the study met one of its secondary endpoints with 78% (32/41) of infants classified as HINE-2*** responders, which evaluated motor function through head control, sitting, voluntary grasp, ability to kick, rolling, crawling, standing and walking. Infants were classified as HINE-2 responders if more motor milestones showed improvement than worsened.

“These data published in the New England Journal of Medicine validate results from Part 1 of the FIREFISH study that showed Evrysdi can help babies with SMA reach the significant milestone of sitting without support for at least five seconds,” said Levi Garraway, M.D., Ph.D., Genentech’s chief medical officer and head of Global Product Development. “These results have been further confirmed in the recently presented 24-month data showing Evrysdi continued to improve motor function, doubling the number of babies able to sit without support from month 12. We will continue to work closely with governments and the SMA community to bring Evrysdi to as many people as possible.”

Safety for Evrysdi in the FIREFISH Part 2 study was consistent with its known safety profile. The most common adverse events were upper respiratory tract infection (68%), pneumonia (39%), pyrexia (39%), constipation (20%), diarrhea (10%) and maculopapular rash (10%). The most common serious adverse events were pneumonia (32%), bronchiolitis (5%), hypotonia (5%) and respiratory failure (5%). Three infants experienced fatal complications of their disease within the first 3 months of treatment. None of these were attributed by the investigator as related to Evrysdi.

In February 2021, 12-month results from the dose finding Part 1 of the FIREFISH study were published in NEJM.

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

*As assessed by the Gross Motor Scale of the Bayley Scales of Infant and Toddler Development Third Edition (BSID-III)

**Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders

***Hammersmith Infant Neurological Examination 2

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

Evrysdi was granted orphan designation by the European Medicines Agency (EMA) in 2019, PRIME designation by the EMA in 2018 and Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) in 2017. Evrysdi has been approved in 54 countries and submitted in a further 33 countries.

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 by the Gross Motor Scale of the Bayley Scales of Infant and Toddler 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 the 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 (inclusion criteria) 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, PK and PD of Evrysdi in babies (~n=25), from birth to 6 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.

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

Before taking Evrysdi, patients should tell their healthcare provider about all of their medical conditions, including if they:
- are pregnant or plan to become pregnant. If patients are pregnant, or are planning to become pregnant, they should ask their healthcare provider for advice before taking this medicine. Evrysdi may harm one’s unborn baby.
- are a woman who can become pregnant:
  - Before patients start their treatment with Evrysdi, their healthcare provider may test them for pregnancy. Because Evrysdi may harm one’s unborn baby, one’s healthcare provider will decide if taking Evrysdi is right for them during this time
  - Patients should talk to their healthcare provider about birth control methods that may be right for them. Patients should use birth control while on treatment and for at least 1 month after stopping Evrysdi
- are an adult male planning to have children: Evrysdi may affect a man’s ability to have children (fertility). If this is of concern to patients, they should make sure to ask a healthcare provider for advice
- are breastfeeding or plan to breastfeed. It is not known if Evrysdi passes into breast milk and may harm one’s baby. If patients plan to breastfeed, they should discuss with their healthcare provider about the best way to feed one’s baby while on treatment with Evrysdi
Patients should tell their healthcare provider about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Patients should keep a list of them to show their healthcare provider and pharmacist when they get a new medicine
Patients should receive Evrysdi from the pharmacy as a liquid that can be given by mouth or through a feeding tube. The liquid solution is prepared by the patient’s pharmacist. If the medicine in the bottle is a powder, do not use it. The patient should contact their pharmacist for a replacement
Avoid getting Evrysdi on one’s skin or in one’s eyes. If Evrysdi gets on one’s skin, wash the area with soap and water. If Evrysdi gets in one’s eyes, rinse one’s 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, sore throat, and cough (upper respiratory infection)
  - lung infection
  - constipation
  - vomiting

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.

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.