Olesoxime

Courtesy gilaxia/Getty Images The World Muscle Society 2022 Congress is ongoing in Halifax, Canada, with numerous companies presenting cutting-edge research in neuromuscular diseases. Here’s a look at presentations from Genentech, Fulcrum Therapeutics and Sarepta Therapeutics. Genentech’s Evrysdi 2-Year Trial for SMA Genentech, a Roche company, presented new two-year data from the JEWELFISH trial of Evrysdi (risdiplam) in patients with Type 1, 2 or 3 spinal muscular atrophy (SMA). The results demonstrated the drug improved or maintained motor function while leading to rapid increases in SMN protein levels that were sustained after two years of receiving Evrysdi. The trial enrolled 174 patients six months to 60 years of age. All had been previously treated with other approved or experimental SMA therapies, including Biogen’s Spinraza (nusinersen). SMA is a genetic disorder beginning in the central nervous system that affects all the muscle in the body. It is the result of a lack of survival motor neuron (SMN) protein, which is essential for muscle development and movement. The company notes that JEWELFISH enrolled “the broadest and most diverse patient population ever studied in an SMA trial.” In addition to the range of ages, two-thirds, or 63%, of the participants were diagnosed as having very severe disease, and 83% had scoliosis. About 44% had previously received Spinraza with olesoxime, and 8% received Novartis’ Zolgensma (onasemnogene abeparvovec) with RG7800. Claudia Chiriboga, M.D., professor of neurology and pediatrics, department of neurology at Columbia University Medical Center, New York, stated the data “reinforces Evrysdi as a meaningful treatment option across SMA populations. The findings add to our confidence when making treatment decisions for previously treated patients in need.” Fulcrum’s FSHD Study of Losmapimod Fulcrum Therapeutics announced new data from the open-label extension (OLE) part of its Phase II ReDUX4 trial of losmapimod for treating FSHD, and it will also host a symposium entitled “Measuring Progression in FSHD: Implications for Clinical Trials.” The data from the OLE support previous results showing the drug modifies FSHD disease progress, preserving or improving muscle function. The ReDUX4 study enrolled 80 patients ages 18 to 65 with genetically confirmed FSHD1. They were randomized 1:1 to receive 15 mg losmapimod twice a day or placebo. After the initial 48-week period, all patients had the choice to enroll in the OLE segment, where all received losmapimod. Of the 77 patients who completed the 48-week segment, 99% enrolled in the OLE. The patients who were originally in the placebo arm who crossed over to losmapimod for the OLE and stayed on the drug through 95 weeks demonstrated trends that the disease was slowing or halting progression as measured by reachable workspace (RWS). The patients who were in the drug cohort initially and stayed for the OLE continued to demonstrate slowing or stopping of disease progression and improvement in muscle function, as measured by RWS. Bryan Stuart, CEO of Fulcrum, emphasized the importance of the data, stating, “The sustained ability to slow or halt the progression of FSHD over two years underscores the significance of our Phase III REACH trial and the potential of losmapimod to be the first approved treatment for FSHD.” Sarepta Presents Range of Programs Across Portfolio Sarepta Therapeutics presented new data from across its genetic medicine portfolio, including real-world evidence on eteplirsen in treated patients with Duchenne muscular dystrophy (DMD) amenable to exon 51 skipping. Sarepta also presented preclinical data from its gene therapy platform in support of the SRP-9001 (delandistrogene moxeparvovec) for treatment of DMD. From its RNA platform, the company presented interim Phase III ESSENCE data on casimersen in DMD patients amenable to Exon 45 skipping and interim analysis of the long-term observational EVOLVE study of eteplirsen, golodirsen or casimersen in routine clinical practice. From the company’s gene therapy programs, Sarepta presented analysis of adeno-associated virus (AAV) vector shedding after treating patients with SRP-9001. The company also presented pharmacokinetic/pharmacodynamic modeling data around AAV gene transfer therapy for DMD, as well as the pharmacology and efficacy of SRP-9001 in rat models of DMD. Sarepta also presented Health Economic Outcomes Research (HEOR) related to DMD treatments.

New two-year Evrysdi data show improvement or maintenance of motor function in people with SMA, a progressive neuromuscular disease that can be fatal The JEWELFISH study enrolled the broadest and most diverse patient population ever studied in an SMA trial Longer-term safety data consistent with that previously seen in earlier trials and low study drop-out rate Evrysdi has proven efficacy in babies, children and adults, with more than 7,000 patients treated to date worldwide SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)-- Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced new two-year data from the JEWELFISH study evaluating Evrysdi® (risdiplam) in people with Type 1, 2 or 3 SMA aged 6 months to 60 years at time of enrollment. Patients had been previously treated with other approved or investigational SMA-targeting therapies, including nusinersen (Spinraza®) or onasemnogene abeparvovec (Zolgensma®). Data showed Evrysdi improved or maintained motor function and led to rapid increases in SMN protein levels which were sustained after two years of treatment. These data will be presented at the 27th World Muscle Society (WMS) congress, October 11-15, 2022. “The consistent safety pro exploratory efficacy we have seen in the JEWELFISH study, the largest ever conducted in previously treated patients, reinforces Evrysdi as a meaningful treatment option across SMA populations,” said Dr. Claudia Chiriboga, Professor of Neurology and Pediatrics, Department of Neurology, Columbia University Medical Center, New York. “The findings add to our confidence when making treatment decisions for previously-treated patients in need.” The JEWELFISH study enrolled the broadest and most diverse patient population ever studied in an SMA trial. Of the 174 people enrolled, 36% (n=63) were adults, 63% (n=105) had a Hammersmith Functional Motor Scale Expanded (HFMSE) score of less than 10 at baseline, meaning their disease was very severe, and 83% (n=139) had scoliosis. Forty-four percent (n=76) of those enrolled had previously been treated with nusinersen (Spinraza), 41% (n=71) with olesoxime*, 8% (n=14) with onasemnogene abeparvovec (Zolgensma) and 7% (n=13) with RG7800*. People with SMA are unable to produce enough survival motor neuron (SMN) protein, leading to debilitating and potentially fatal muscle weakness. The study showed Evrysdi led to a two-fold increase in median SMN protein levels versus baseline after four weeks of treatment in all patient groups, irrespective of previous treatment. The SMN protein levels achieved after four weeks of treatment were maintained for over two years. Observed through exploratory efficacy endpoints, the study also suggests maintenance of motor function was sustained at two years of treatment as measured by change from baseline in Motor Function Measure 32 (MFM-32), Revised Upper Limb Module (RULM) and HFMSE total scores compared to the natural history of SMA in untreated patients. A recent survey conducted by patient advocacy group SMA Europe showed that more than 96% of people with SMA viewed disease stabilization as progress in terms of their expectations of treatment. “These important data demonstrate the safety and efficacy of Evrysdi in a broad, real-world population of people previously treated with an SMA-targeting therapy,” said Levi Garraway, M.D., Ph.D., Genentech’s chief medical officer and head of Global Product Development. “Those enrolled in JEWELFISH had very severe disease, with over 80% having scoliosis, so maintaining motor function–especially for a progressive disease–can be potentially life-changing.” The overall adverse event (AE) and serious adverse event (SAE) profiles observed with Evrysdi treatment in JEWELFISH were reflective of underlying disease. The rate of AEs decreased by more than 50% between the first and second six-month period, and then remained stable thereafter. The rate of SAEs, including pneumonia, decreased throughout the 24-month period, with a total reduction of more than 50% by the second year. The most common AEs (reported in ≥12% of all patients; n=173) were pyrexia (24%), upper respiratory tract infection (21%), headache (18%), nasopharyngitis (16%), diarrhea (14%), nausea (13%) and cough (12%). The most common SAEs (reported in >2% of all patients) were pneumonia (3%), respiratory failure (2%), respiratory distress (2%), lower respiratory tract infection (2%) and upper respiratory tract infection (2%). The most common AEs/SAEs were consistent with those observed in treatment-naïve patients in our other three trials. Low rates of discontinuation from the study were observed, with a 5% rate per year over the 24-month period. Genentech leads the clinical development of Evrysdi as part of a collaboration with the SMA Foundation and PTC Therapeutics. *RG7800 and olesoxime are no longer in development as investigational treatments for patients with SMA. 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 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 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 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 91 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. Part 1 was a dose-escalation study in 21 infants with the primary objective of assessing the safety pro risdiplam in infants and determining the dose for Part 2. Part 2 is a pivotal, single-arm study of risdiplam in 41 infants with Type 1 SMA treated for two 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 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 risdiplam 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 ongoing. MANATEE (NCT05115110) – a global phase 2/3 clinical study to evaluate the safety and efficacy of GYM329 (RO7204239), 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 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 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 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 pro Evrysdi, ask your healthcare provider or pharmacist. You may report side effects to the FDA at 1-800-FDA-1088 or . You may also report side effects to Genentech at 1-888-835-2555. Please see full Prescribing Information for additional Important Safety Information. 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 . View source version on businesswire.com: Contacts Media Contact: Adam Pryor, (650) 467-6800 Advocacy Contact: Alana Paull, (925) 528-1014 Investor Contacts: Loren Kalm, (650) 225-3217 Bruno Eschli, +41 61 68-75284 Source: Genentech View this news release online at: