CAMBRIDGE, Mass.--(BUSINESS WIRE)--Biogen (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). 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
ENDEAR is a randomized,
double-blind, sham-procedure controlled 13-month study in patients with
infantile-onset SMA. The end of study efficacy analysis included all
patients (n=121) who had their final study visit after the interim
analysis (n=78) and had the opportunity to attend the six-month study
visit assessment. The Hammersmith Infant Neurological Examination (HINE)
is a reliable and clinically validated tool to assess motor milestone
achievement in infants with SMA.
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
SPINRAZA is the first approved
medicine for the treatment of SMA and is currently approved in the
United States, the European Union, Brazil, Japan and Canada. Biogen has
submitted regulatory filings in additional countries and plans to
initiate additional filings in other countries.
Globally, in 2016, in response to the urgent need for treatment for the most 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
Spinal muscular atrophy (SMA)
is characterized by loss of motor neurons in the spinal cord and lower
brain stem, resulting in severe and progressive muscular atrophy and
weakness. Ultimately, individuals with the most severe type of SMA can
become paralyzed and have difficulty performing the basic functions of
life, like breathing and swallowing.
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 being developed globally for the treatment of SMA.
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
Through cutting-edge science and medicine,
Biogen discovers, develops and delivers innovative therapies worldwide
for people living with serious neurological and neurodegenerative
diseases. Founded in 1978, Biogen is a pioneer in biotechnology and
today the Company has the leading portfolio of medicines to treat
multiple sclerosis, has introduced the first and only approved treatment
for spinal muscular atrophy and is at the forefront of neurology
research for conditions including Alzheimer’s disease, Parkinson’s
disease and amyotrophic lateral sclerosis. Biogen also manufactures and
commercializes biosimilars of advanced biologics. For more information,
please visit www.biogen.com.
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Biogen Safe Harbor
This press release contains
forward-looking statements, including statements made pursuant to the
safe harbor provisions of the Private Securities Litigation Reform Act
of 1995 relating to the potential benefits, safety and efficacy of
SPINRAZA, the results of certain real-world data, the status of current
regulatory filings, plans for additional regulatory filings in other
jurisdictions, planning and timing for commercial launch, and
availability of patient access and reimbursement pathways, which may
vary on a country-by-country basis. These forward-looking statements may
be accompanied by words such as “aim,” “anticipate,” “believe,” “could,”
“estimate,” “except,” “forecast,” “intend,” “may,” “plan,” “potential,”
“possible,” “will” and other words and terms of similar meaning. You
should not place undue reliance on these statements or the scientific
data presented. Drug development and commercialization involve a high
degree of risk. These statements involve risks and uncertainties that
could cause actual results to differ materially from those reflected in
such statements, including without limitation uncertainty of success in
commercialization of SPINRAZA, which may be impacted by, among other
things, the level of preparedness of healthcare providers to treat
patients, difficulties in obtaining or changes in the availability of
reimbursement for SPINRAZA, the effectiveness of sales and marketing
efforts, problems with the manufacturing process for SPINRAZA, the
occurrence of adverse safety events, unexpected concerns that may arise
from additional data or analysis; regulatory authorities may require
additional information or further studies, or may fail to approve or may
delay approval of Biogen’s drug candidates or expansion of product
labeling; or Biogen may encounter other unexpected hurdles which may be
impacted by, among other things, the occurrence of adverse safety
events, failure to obtain regulatory approvals in certain jurisdictions,
failure to obtain regulatory approvals in other jurisdictions, failure
to protect intellectual property and other proprietary rights; product
liability claims; or third party collaboration risks. The foregoing sets
forth many, but not all, of the factors that could cause actual results
to differ from our expectations in any forward-looking statement.
Investors should consider this cautionary statement, as well as the risk
factors identified in Biogen’s most recent annual or quarterly report
and in other reports Biogen has filed with the U.S. Securities and
Exchange Commission. These statements are based on our current beliefs
and expectations and speak only as of the date of this press release. We
do not undertake any obligation to publicly update any forward-looking
statements, whether as a result of new information, future developments
or otherwise.
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 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.
