First SMA Treatment Recommended for Approval in the EU
(NASDAQ: BIIB) today announced the Committee for Medicinal Products for
Human Use (CHMP) of the European Medicines Agency (EMA) adopted a
positive opinion recommending the granting of a marketing authorization
for SPINRAZA® (nusinersen) to treat patients with spinal
muscular atrophy (SMA). The CHMP reviewed SPINRAZA under an accelerated
assessment program, which is a regulatory mechanism to facilitate
earlier access to patients for medicines that fulfill unmet medical
needs. SPINRAZA is the first treatment for SMA to be recommended by the
CHMP for approval in the European Union (EU).
“The positive CHMP opinion, which was expedited under the accelerated
assessment program, recognizes the compelling efficacy profile of
SPINRAZA and underscores the significant unmet need for an effective SMA
treatment in Europe,” said Michael Ehlers, M.D., Ph.D., executive vice
president, Research and Development at Biogen. “We look forward to the
European Commission’s decision and believe SPINRAZA has the potential to
make a meaningful impact for individuals with SMA in the EU.”
The CHMP positive opinion is now referred to the European Commission
(EC), which grants the marketing authorization for centrally authorized
medicines in the EU. The CHMP recommended an indication for the
treatment of 5q SMA, which refers to the most common form of the disease
and represents approximately 95% of all SMA cases.1 A
decision from the EC is expected in the next few months.
Data Supporting Positive OpinionThe recommendation was
primarily based on the CHMP’s assessment of two pivotal controlled
studies, ENDEAR (infantile-onset SMA) and CHERISH (later-onset SMA),
which both demonstrated the clinically meaningful efficacy and favorable
safety profile of SPINRAZA.
In ENDEAR, a statistically significant greater percentage of
individuals with infantile-onset SMA (most likely to develop Type 1)
treated with SPINRAZA achieved a motor milestone response compared to
untreated individuals. Motor milestones achieved in some individuals
treated with SPINRAZA included the ability to kick, head control,
rolling, sitting and crawling. In addition, a statistically
significant reduction in the risk of death or permanent ventilation
was seen in SPINRAZA-treated individuals compared to untreated
individuals at the end of study analysis.
In CHERISH, there was a statistically significant and clinically
meaningful improvement in motor function in individuals treated with
SPINRAZA with later-onset SMA (most likely to develop Type 2 or Type
3) compared to untreated individuals at the interim analysis.
Improvements were measured by the Hammersmith Functional Motor Scale
Expanded (HFMSE). The HFMSE is a reliable and validated tool
specifically designed to assess motor function in children with SMA.
Data from open-label studies in pre-symptomatic and symptomatic
individuals most likely to develop Type 1, 2 or 3 were consistent with
the results of the pivotal studies and were considered supportive of
the recommended indication. The overall findings of these studies
support the efficacy and safety of SPINRAZA in individuals with SMA.
SPINRAZA demonstrated a favorable safety profile. SPINRAZA is to be
administered by healthcare professionals experienced in doing lumbar
punctures due to the risks associated with this procedure (e.g.
headache, backpain, vomiting).
SPINRAZA Program StatusBiogen 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 by the United States Food and Drug Administration
(FDA) in 2016.2
SPINRAZA was first approved by the FDA on December 23, 2016 within three
months of regulatory filing. Biogen has also submitted regulatory
filings in Japan, Canada, Australia and Switzerland and plans to
initiate additional filings in other countries in 2017.
About SMA3-7Spinal 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 survival motor neuron (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) 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.8 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
SPINRAZA is administered via intrathecal injection, which delivers
therapies directly to the cerebrospinal fluid (CSF) around the spinal
cord,9 where motor neurons degenerate in patients with SMA
due to insufficient levels of SMN protein.10
There is a risk of adverse reactions occurring as part of the lumbar
puncture procedure (e.g. headache, backpain, vomiting). Coagulation
abnormalities and thrombocytopenia, including acute severe
thrombocytopenia, have been observed after administration of some
antisense oligonucleotides. Renal toxicity has been observed after
administration of some antisense oligonucleotides.
About BiogenThrough 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 HarborThis press release contains
forward-looking statements, including statements relating to the
potential benefits, safety and efficacy of SPINRAZA, the status of
current regulatory filings, and plans for additional regulatory filings
in other jurisdictions. These statements may be identified by words such
as “believe,” “except,” “may,” “plan,” “potential,” “will” and similar
expressions, and are based on our current beliefs and expectations. You
should not place undue reliance on these statements. These statements
involve risks and uncertainties that could cause actual results to
differ materially from those reflected in such statements, including
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, failure to obtain
regulatory approvals in other jurisdictions, failure to protect
intellectual property and other proprietary rights, product liability
claims, third party collaboration risks, and the other risks and
uncertainties that are described in the Risk Factors section of Biogen’s
most recent annual or quarterly report and in other reports Biogen has
filed with the U.S. Securities and Exchange Commission (SEC). Any
forward-looking statements speak only as of the date of this press
release and we assume no obligation to update any forward-looking
1. Farrar MA, Kiernan MC. The Genetics of Spinal Muscular Atrophy:
Progress and Challenges. Neurotherapeutics; 2015; 12:290–302.
2. Biogen. SPINRAZA USPI. December 2016.
3. 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.
4. Lefebvre S, Burglen L, Reboullet S, et al. Identification and
characterization of a spinal muscular atrophy-determining gene. Cell.
5. Mailman MD, Heinz JW, Papp AC, et al. Molecular analysis of spinal
muscular atrophy and modification of the phenotype by SMN2. Genet Med.
6. 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.
7. Peeters K, Chamova T, Jordanova A. Clinical and genetic diversity of
SMN1-negative proximal spinal muscular atrophies. Brain.
8. 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.
9. Evers MM, Toonen LJ, van Roon-Mom WM. Antisense oligonucleotides in
therapy for neurodegenerative disorders. Adv Drug Deliv Rev. 2015;87:90-103.
10. Lunn MR, Wang CH. Spinal muscular atrophy. Lancet.
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