– Evrysdi (risdiplam) 2-year FIREFISH Part 2 data show improvement in motor function in infants with Type 1 spinal muscular atrophy (SMA) –
– Ocrevus (ocrelizumab) data show its consistent benefit on slowing disease progression in relapsing multiple sclerosis (RMS) and primary progressive MS (PPMS) –
– Data for Enspryng (satralizumab-mwge) in neuromyelitis optica spectrum disorder (NMOSD) reinforce safety and efficacy, including in patients with concomitant autoimmune diseases (CAIDs) –
– Data for investigational MS medicine fenebrutinib support its safety profile and high potency –
– Additional presentations on investigational programs, including Alzheimer’s disease and Huntington’s disease, help advance scientific understanding of neurological disorders –
SOUTH SAN FRANCISCO, Calif.–(BUSINESS WIRE)–Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that new data for its approved and investigational medicines for the treatment of neurological disorders will be presented at the 73rd American Academy of Neurology (AAN) Annual Meeting being held virtually April 17-22, 2021. These new data include 23 abstracts highlighting the expanding Genentech neuroscience portfolio across six therapeutic areas, including Evrysdi™ (risdiplam) for spinal muscular atrophy (SMA), Ocrevus® (ocrelizumab) in relapsing and primary progressive multiple sclerosis (RMS and PPMS), investigational Bruton’s tyrosine kinase inhibitor (BTKi) fenebrutinib in Phase III trials for RMS and PPMS, Enspryng™ (satralizumab-mwge) in neuromyelitis optica spectrum disorder (NMOSD), and data from investigational programs in Alzheimer’s disease (AD) and Huntington’s disease (HD).
“Following U.S. FDA and global approvals for our groundbreaking therapies in SMA and NMOSD, Roche and Genentech’s data at AAN reflect our continued commitment to meaningful therapeutic progress for people living with neurological disorders,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “We are proud to collaborate with patient advocates, academia, industry and the broader healthcare community through cutting-edge research and partnerships to advance the scientific understanding of neurological conditions, which have historically been among the hardest disorders to study, diagnose and treat.”
Spinal Muscular Atrophy (SMA)
Genentech will present data from five studies from the Evrysdi clinical development program, which was designed to represent a broad spectrum of people living with SMA. The program includes infants aged 2 months to adults aged 60 years with varying degrees of disability, including people with scoliosis or joint contractures, and those previously treated for SMA with another medication.
New 2-year findings from Part 2 of the Phase II/III FIREFISH trial show longer-term efficacy and safety of Evrysdi in infants with symptomatic Type 1 SMA treated with Evrysdi. This includes the number of infants able to sit without support for 5 and 30 seconds, a key motor milestone not normally seen in the natural course of the disease, as well as data on event-free survival and reduced hospitalizations.
Additional data being presented across Evrysdi’s broad clinical trial program include updated data from the JEWELFISH trial evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics of Evrysdi in patients previously treated with SMA-targeting therapies, as well as updated pooled safety analyses from the FIREFISH, SUNFISH, RAINBOWFISH and JEWELFISH trials.
Multiple Sclerosis (MS)
Genentech will present data from its MS franchise, including five presentations covering Ocrevus and results from studies on the investigational BTKi fenebrutinib. Real-world data continue to show the highest persistence and adherence to Ocrevus, the only MS therapy with a twice-yearly dosing schedule, over one year compared to other disease-modifying therapies (DMTs). Additionally, a post-hoc analysis of the ORATORIO Phase III PPMS study will be presented, which suggests Ocrevus significantly slowed atrophied T2-lesion volume accumulation, a subclinical measure of disease progression. Furthermore, interim analysis of the open-label Phase IIIb ENSEMBLE study shows Ocrevus treatment provided consistent benefit over one year in patients who were recently diagnosed with relapsing-remitting multiple sclerosis (RRMS) and had not received prior DMT.
Genentech is continuing to advance the science in MS and is exploring the investigational medicine fenebrutinib. Data from fenebrutinib, a highly selective, non-covalent, reversible oral BTKi, support its safety profile in several autoimmune diseases and high potency, which is encouraging for the ongoing Phase III studies in RMS and PPMS. Fenebrutinib is a dual inhibitor of both B-cell and myeloid lineage-cell activation, which may offer a novel approach to slowing disease progression by targeting both acute and chronic inflammatory aspects of MS.
Neuromyelitis Optica Spectrum Disorder (NMOSD)
Genentech will present five sets of data on adults living with NMOSD. Data from the Phase III SAkuraStar and SAkuraSky clinical trials reinforce the favorable safety and efficacy of this therapy for those living with NMOSD, including patients with concomitant autoimmune diseases (CAIDs).
New longitudinal, observational data from the CIRCLES study, conducted in collaboration with the Guthy-Jackson Charitable Foundation, a patient advocacy organization dedicated to funding research on NMOSD epidemiology, pathogenesis and treatment, also will be presented. The CIRCLES study explored factors that influence treatment change in people living with NMOSD, including those who have experienced only one relapse.
Alzheimer’s Disease (AD)
Genentech will present data on the increased use of home nursing capabilities in the Phase III GRADUATE studies of gantenerumab during the COVID-19 pandemic, which enabled home-bound trial participants to continue dosing to maintain medicine exposure.
Gantenerumab is a late-stage investigational anti-beta-amyloid antibody being evaluated in two Phase III studies (GRADUATE I and II), which are the only late-stage AD clinical trials to offer subcutaneous administration. Data from the studies is expected in 2022.
Huntington’s Disease (HD)
Genentech also will present an analysis of the Enroll-HD study and REGISTRY database, which highlight the role that genetic factors and medical history may have in predicting the rate of disease progression in HD. These data may help advance the understanding of HD and inform future treatment approaches for this rare, neurological condition.
The full range of data from Genentech’s clinical development program in neuroscience being presented at AAN 2021 include:
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Medicine and/or |
Abstract Title
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Presentation Number |
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Evrysdi
Muscular |
FIREFISH Part 2: 24-month Efficacy and Safety of Risdiplam in Infants with Type 1 Spinal Muscular Atrophy (SMA) |
P6.062 |
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SUNFISH Part 2: 24-month Efficacy and Safety of Risdiplam in Patients with Type 2 or Non-ambulant Type 3 Spinal Muscular Atrophy (SMA) |
P6.060 |
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JEWELFISH: Safety and Pharmacodynamic Data in Non-naïve Patients with Spinal Muscular Atrophy (SMA) Receiving Treatment with Risdiplam |
P6.064 |
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Pooled Safety Data from the Risdiplam Clinical Trial Development Program |
P6.067 |
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RAINBOWFISH: A study of Risdiplam in Newborns with Presymptomatic Spinal Muscular Atrophy (SMA) |
P6.076 |
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Ocrevus |
B-Cell Subset Depletion Following Ocrelizumab Treatment in Patients with Relapsing Multiple Sclerosis |
P15.206 |
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Evolution of Lesions that Shrink or Disappear into Cerebrospinal Fluid (Atrophied T2 Lesion Volume) in Primary-Progressive Multiple Sclerosis: Results from the Phase III ORATORIO Study |
P15.151 |
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Recently Diagnosed Early-Stage RRMS: NEDA, ARR, Disability Progression, Serum Neurofilament and Safety: 1-Year Interim Data from the Ocrelizumab Phase IIIb ENSEMBLE Study |
P15.099 |
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Adherence and Persistence to Disease-modifying Therapies for Multiple Sclerosis and Their Impact on Clinical and Economic Outcomes in a U.S. Claims Database |
P15.228 |
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Safety of Ocrelizumab in Multiple Sclerosis: Updated Analysis in Patients with Relapsing and Primary Progressive Multiple Sclerosis |
P15.203 |
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Fenebrutinib for |
The Safety of Fenebrutinib in a Large Population of Patients with Diverse Autoimmune Indications Supports Investigation in Multiple Sclerosis (MS)
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S25.005 (oral presentation) |
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Fenebrutinib Demonstrates the Highest Potency of Bruton Tyrosine Kinase Inhibitors (BTKis) in Phase 3 Clinical Development for Multiple Sclerosis (MS) |
P15.091 P15: MS Clinical Trials and Therapeutics |
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Enspryng
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Satralizumab in Patients with Neuromyelitis Optica Spectrum Disorder and Concomitant Autoimmune Disease |
P2.019 |
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Neuromyelitis |
Disease Phenotype Correlates with Treatment Change in NMOSD Patients of the CIRCLES Cohort |
P2.091 |
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Demographic and Relapse Correlates of Treatment Change in NMOSD Patients: Analysis of the CIRCLES Study
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P2.013 |
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Relapse Profile Correlates with Treatment Change in NMOSD Patients of the CIRCLES Cohort
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P2.012 |
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Correlates of Rituximab Discontinuation in Patients with NMOSD: a CIRCLES Cohort Analysis
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P2.014 |
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Alzheimer’s |
Linking Amyloid to Cognition in the Pathogenesis and Treatment of Alzheimer’s Disease: Toward the Development of a “Quantitative A/T/N Model” |
P1.052 |
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Gantenerumab |
Utilization of Home Nursing to Mitigate the Impact of COVID-19 on the Conduct of the Gantenerumab GRADUATE Trials |
P1.014 |
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Semorinemab for Alzheimer’s |
A Disease Progression Model for Alzheimer’s Disease Predicts Longitudinal Trajectory of CDR-SB Score Across Different Stages of the Disease |
P1.061 |
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Huntington’s |
Burden of Illness among U.S. Medicare Beneficiaries with Late-onset Huntington’s Disease |
P14.043
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Clinical Characteristics of Late-onset Huntington’s Disease in North Americans from the Enroll-HD Study |
P14.046
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Clustering and Prediction of Disease Progression Trajectories in Huntington’s Disease: An Analysis of the Enroll-HD and REGISTRY Database Using a Machine Learning Approach |
P14.147 |
About spinal muscular atrophy
Spinal muscular atrophy (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.
About Evrysdi™ (risdiplam)
Evrysdi is a survival of motor neuron 2 (SMN2) splicing modifier designed to treat SMA by increasing and sustaining 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 in August of 2020. In March 2021, the European Commission (EC) approved Evrysdi for the treatment of 5q SMA in patients 2 months of age and older, with a clinical diagnosis of SMA Type 1, Type 2 or Type 3 or with one to four SMN2 copies. Evrysdi has been approved in 38 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 in 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 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 6 weeks of age (at first dose) with genetically diagnosed SMA who are not yet presenting with symptoms. The study is currently recruiting.
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
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Before taking Evrysdi, patients should tell their healthcare provider about all of their medical conditions, including if they:
- have liver problems
- 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.
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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
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The most common side effects of Evrysdi include:
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For later-onset SMA:
- fever
- diarrhea
- rash
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For infantile-onset SMA:
- fever
- diarrhea
- rash
- runny nose, sneezing, sore throat, and cough (upper respiratory infection)
- lung infection
- constipation
- vomiting
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For later-onset SMA:
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 multiple sclerosis
Multiple sclerosis (MS) is a chronic disease that affects nearly one million people in the United States, for which there is currently no cure. MS occurs when the immune system abnormally attacks the insulation and support around nerve cells (myelin sheath) in the brain, spinal cord and optic nerves, causing inflammation and consequent damage. This damage can cause a wide range of symptoms, including muscle weakness, fatigue and difficulty seeing, and may eventually lead to disability. Most people with MS experience their first symptom between 20 and 40 years of age, making the disease the leading cause of non-traumatic disability in younger adults.
Relapsing-remitting MS (RRMS) is the most common form of the disease and is characterized by episodes of new or worsening signs or symptoms (relapses) followed by periods of recovery. Approximately 85% of people with MS are initially diagnosed with RRMS. The majority of people who are diagnosed with RRMS will eventually transition to secondary progressive MS (SPMS), in which they experience steadily worsening disability over time. Relapsing forms of MS (RMS) include people with RRMS and people with SPMS who continue to experience relapses. Primary progressive MS (PPMS) is a debilitating form of the disease marked by steadily worsening symptoms but typically without distinct relapses or periods of remission. Approximately 15% of people with MS are diagnosed with the primary progressive form of the disease. Until the FDA approval of Ocrevus, there had been no FDA approved treatments for PPMS.
People with all forms of MS experience disease activity – inflammation in the nervous system and permanent loss of nerve cells in the brain – even when their clinical symptoms aren’t apparent or don’t appear to be getting worse. An important goal of treating MS is to reduce disease activity as soon as possible to slow how quickly a person’s disability progresses. Despite available disease-modifying treatments (DMTs), some people with RMS continue to experience disease activity and disability progression.
About Ocrevus® (ocrelizumab)
Ocrevus is the first and only therapy approved for both RMS (including clinically isolated syndrome, RRMS and active, or relapsing, SPMS) and PPMS, with dosing every six months. Ocrevus is a humanized monoclonal antibody designed to target CD20-positive B cells, a specific type of immune cell thought to be a key contributor to myelin (nerve cell insulation and support) and axonal (nerve cell) damage. This nerve cell damage can lead to disability in people with MS. Based on preclinical studies, Ocrevus binds to CD20 cell surface proteins expressed on certain B cells, but not on stem cells or plasma cells, suggesting that important functions of the immune system may be preserved.
Ocrevus is administered by intravenous infusion every six months. The initial dose is given as two 300 mg infusions given two weeks apart. Subsequent doses are given as single 600 mg infusions.
Indications and Important Safety Information
What is Ocrevus?
Ocrevus is a prescription medicine used to treat:
- Relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults
- Primary progressive MS, in adults.
It is not known if Ocrevus is safe or effective in children.
Who should not receive Ocrevus?
Do not receive Ocrevus if you have an active hepatitis B virus (HBV) infection.
Do not receive Ocrevus if you have had a life threatening allergic reaction to Ocrevus. Tell your healthcare provider if you have had an allergic reaction to Ocrevus or any of its ingredients in the past.
What is the most important information I should know about Ocrevus?
Ocrevus can cause serious side effects, including:
- Infusion reactions: Infusion reactions are a common side effect of Ocrevus, which can be serious and may require you to be hospitalized. You will be monitored during your infusion and for at least 1 hour after each infusion of Ocrevus for signs and symptoms of an infusion reaction. Tell your healthcare provider or nurse if you get any of these symptoms:
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These infusion reactions can happen for up to 24 hours after your infusion. It is important that you call your healthcare provider right away if you get any of the signs or symptoms listed above after each infusion.
If you get infusion reactions, your healthcare provider may need to stop or slow down the rate of your infusion.
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Infection:
- Ocrevus increases your risk of getting upper respiratory tract infections, lower respiratory tract infections, skin infections, and herpes infections. Infections are a common side effect, which can be serious. Tell your healthcare provider if you have an infection or have any of the following signs of infection including fever, chills, or a cough that does not go away. Signs of herpes include cold sores, shingles, genital sores, skin rash, pain, and itching. Signs of more serious herpes infection include: changes in vision, eye redness or eye pain, severe or persistent headache, stiff neck, and confusion.
Contacts
Media Contact: Justin Hurdle (650) 467-6800
Advocacy Contact: JP Sacksteder (650) 666-7329
Investor Contacts: Lisa Tuomi (650) 467-8737
Karl Mahler 011 41 61 687 8503