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Biogen's SPINRAZA® (nusinersen) Data Show Earlier Treatment Initiation May Lead to Improved Motor Function Across a Broad Population of People Living with Spinal Muscular AtrophyBiogen (NASDAQ: BIIB) presented new data demonstrating that earlier initiation of treatment with SPINRAZA® (nusinersen) may improve motor function outcomes in infants and children with spinal muscular atrophy (SMA (News - Alert)). Results continued to reinforce the favorable efficacy and safety profile of SPINRAZA. The data were shared at the 22nd International Annual Congress of the World Muscle Society in Saint Malo, France (October 3-7, 2017). A new analysis from the Phase 3 ENDEAR study showed infants with SMA who initiated treatment earlier in the disease (shorter disease duration) demonstrated greater benefit and improvement in motor function outcomes. As measured by the Hammersmith Infant Neurological Examination (HINE), significant differences in motor milestone responders were observed between infants treated with SPINRAZA compared to untreated infants with disease duration less than or equal to 12 weeks (75% vs. 0%; P<.0001) and those with disease duration greater than 12 weeks (32% vs. 0%; P=.0026). There was also a significant benefit in event-free survival in infants treated with SPINRAZA with disease duration less than or equal to 12 weeks (P=.0004). "These studies contribute to a growing body of evidence that SPINRAZA can make a meaningful difference in the lives of people with SMA regardless of their age or stage of the disease," said Alfred Sandrock, M.D., Ph.D., executive vice president and chief medical officer at Biogen. "Across studies, we continue to see evidence that earlier initiation of treatment with SPINRAZA can lead to improved clinical and functional outcomes." Interim analyses were also presented from the Phase 2 EMBRACE study which was designed to assess the efficacy and safety of SPINRAZA in individuals with infantile- and later-onset SMA who were ineligible for the two earlier pivotal studies. The EMBRACE interim analysis showed a larger proportion of infants and children treated with SPINRAZA were HINE motor milestone responders compared to those who were untreated. Results from the interim analysis also supported the dosing regimen of four loading doses in the first two months, followed by the administration of SPINRAZA every four months thereafter, for individuals with infantile- and later-onset SMA. In the ENDEAR and EMBRACE studies SPINRAZA demonstrated a favorable benefit-risk profile. Safety data involving the intrathecal administration of SPINRAZA showed the incidence and nature of the most common lumbar puncture-related adverse events in the clinical studies were similar in children with later-onset SMA with or without scoliosis. For more information about SPINRAZA and prescribing information in the United States, please visit www.SPINRAZA.com. Prescribing information in the European Union is available at http://www.ema.europa.eu/ema/.
About ENDEAR and EMBRACE EMBRACE is a Phase 2, multicenter, randomized, double-blind, sham-procedure controlled 14-month study of SPINRAZA in infants and children not eligible to participate in ENDEAR (symptom onset less than or equal to six months, less than or equal to seven months of age at screening; 2 SMN2 copies) or CHERISH (symptom onset age greater than six months, age 2-12 years at screening).
SPINRAZA Program Status Globally, in 2016, in response to the urgent need for treatment for the mot severely affected individuals living with SMA, Biogen sponsored one of the largest, pre-approval Expanded Access Programs (EAP) in rare disease, free of charge. Biogen licensed the global rights to develop, manufacture and commercialize SPINRAZA from Ionis Pharmaceuticals (NASDAQ: IONS), a leader in antisense therapeutics. Biogen and Ionis conducted an innovative clinical development program that moved SPINRAZA from its first dose in humans in 2011 to its first regulatory approval in five years.
About SMA1-5 Due to a loss of, or defect in, the SMN1 gene, people with SMA do not produce enough SMN protein, which is critical for the maintenance of motor neurons. The severity of SMA correlates with the amount of SMN protein. People with Type 1 SMA, the form that requires the most intensive and supportive care, produce very little SMN protein and do not achieve the ability to sit without support or live beyond two years without respiratory support. People with Type 2 and Type 3 SMA produce greater amounts of SMN protein and have less severe, but still life-altering forms of SMA.
About SPINRAZA® (nusinersen) SPINRAZA is an antisense oligonucleotide (ASO), using Ionis Pharmaceuticals' proprietary antisense technology, that is designed to treat SMA caused by mutations or deletions in the SMN1 gene located in chromosome 5q that leads to SMN protein deficiency. SPINRAZA alters the splicing of SMN2 pre-mRNA in order to increase production of full-length SMN protein.6 ASOs are short synthetic strings of nucleotides designed to selectively bind to target RNA and regulate gene expression. Through use of this technology, SPINRAZA has the potential to increase the amount of full-length SMN protein in individuals with SMA. SPINRAZA must be administered via intrathecal injection, which delivers therapies directly to the cerebrospinal fluid (CSF) around the spinal cord,7 where motor neurons degenerate in individuals with SMA due to insufficient levels of survival motor neuron (SMN) protein.8 SPINRAZA demonstrated a favorable benefit-risk profile. The most common adverse reactions reported for SPINRAZA were upper respiratory infection, lower respiratory infection and constipation. Serious adverse reactions of atelectasis were more frequent in SPINRAZA-treated patients. Coagulation abnormalities and thrombocytopenia, including acute severe thrombocytopenia, have been observed after administration of some antisense oligonucleotides. Individuals may be at increased risk of bleeding complications. Renal toxicity has been observed after administration of some antisense oligonucleotides. SPINRAZA is present in and excreted by the kidney.
About Biogen
Biogen Safe Harbor 1. Darras B, Markowitz J, Monani U, De Vivo D. Chapter 8 - Spinal Muscular Atrophies. In: Vivo BTD, ed. Neuromuscular Disorders of Infancy, Childhood, and Adolescence (Second Edition). San Diego: Academic Press; 2015:117-145. 2. Lefebvre S, Burglen L, Reboullet S, et al. Identification and characterization of a spinal muscular atrophy-determining gene. Cell.1995;80(1):155-165. 3. Mailman MD, Heinz JW, Papp AC, et al. Molecular analysis of spinal muscular atrophy and modification of the phenotype by SMN2. Genet Med. 2002;4(1):20-26. 4. Monani UR, Lorson CL, Parsons (News - Alert) DW, et al. A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN1 from the copy gene SMN2. Hum Mol Genet. 1999;8(7):1177-1183. 5. Peeters K, Chamova T, Jordanova A. Clinical and genetic diversity of SMN1-negative proximal spinal muscular atrophies. Brain.2014;137(Pt 11):2879-2896. 6. Hua Y, Sahashi K, Hung G, Rigo F, Passini MA, Bennett CF, Krainer AR. Antisense correction of SMN2 splicing in the CNS rescues necrosis in a type III SMA mouse model. Genes Dev. 2010 Aug 1; 24(15):16344-44. 7. Evers MM, Toonen LJ, van Roon-Mom WM. Antisense oligonucleotides in therapy for neurodegenerative disorders. Adv Drug Deliv Rev. 2015;87:90-103. 8. Lunn MR, Wang CH. Spinal muscular atrophy. Lancet. 2008;371(9630):2120-2133.
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