New SPINRAZA® (nusinersen) Data Presented at Annual Congress of the
World Muscle Society Demonstrate Benefits in Treating
Presymptomatic Infants with Spinal Muscular Atrophy
Biogen Inc. (Nasdaq: BIIB) today announced new interim results from
NURTURE, an ongoing open-label, single-arm efficacy and safety
study of SPINRAZA® (nusinersen) in 25 presymptomatic infants with
SMA. The data are being presented today in a late-breaking session
at the 23rd Annual Congress of the World Muscle Society (WMS) held
in Mendoza, Argentina.
“The NURTURE study results demonstrate that early diagnosis and
treatment with SPINRAZA has the potential to dramatically change
the course of SMA,” said Wildon Farwell, M.D., senior medical
director, clinical development at Biogen. “This is the longest
available span of data on infants with SMA who began treatment in a
presymptomatic period and indicates that children treated early
with SPINRAZA can achieve motor milestones they would likely not
attain without treatment.”
The interim analysis evaluated survival and respiratory
intervention rates in infants (n=25) who were genetically diagnosed
with SMA and began treatment in the presymptomatic stage of the
disease. As of May 2018 all patients in the study were alive and
none required tracheostomy or permanent ventilation. Additionally,
22 of the 25 participants were able to walk either with assistance
or independently according to the motor milestone standard of the
World Health Organization and all 25 were able to sit without
support.
The motor skills of study participants were also evaluated using
the Children’s Hospital of Philadelphia Infant Test of
Neuromuscular Disorders (CHOP INTEND), an assessment which
considers 16 different types of movement to create an overall score
between zero and 64. The mean CHOP INTEND scores were 62.6 for
study participants with three copies of the SMN2 gene and 61.0 for
those with two copies of the gene.
All NURTURE study participants were 14 months or older at the
time of the analysis. Participants included infants with two copies
of the SMN2 gene (n=15) who are likely to develop a fatal,
early-onset form of SMA known as Type 1, and infants with three
copies of the SMN2 gene (n=10) who typically develop SMA Type 2 or
3. People living with SMA Types 2 and 3 may never be able to walk
or will lose that ability over time. No new safety concerns were
identified.
Additional research presented at WMS compared levels of
phosphorylated neurofilament heavy chain (pNF-H) in plasma in more
than 300 patients from SPINRAZA clinical trials, including those in
the NURTURE study, and a control group of people without SMA. The
data demonstrated that treatment with SPINRAZA is associated with a
rapid decline followed by stabilization of pNF-H in plasma at
levels close to those of healthy controls. The results are part of
Biogen’s ongoing work to identify and validate biomarkers that
could provide insight on the disease progression of SMA.
“We continue to develop tools to inform our clinical research
and are encouraged by the potential of neurofilament as a biomarker
for SMA, how it could further expand the scientific understanding
of this rare disease and, more importantly, its potential impact on
those living with SMA,” continued Farwell.
SPINRAZA Program Status
SPINRAZA is the first and only approved medicine for the
treatment of spinal muscular atrophy (SMA) and is currently
approved in the U.S., the European Union, Japan and Brazil, among
other countries. Biogen has submitted regulatory filings in
additional countries and plans to initiate additional filings in
other countries. As of June 30, 2018, more than 5,000 individuals
with SMA are being treated with SPINRAZA worldwide, based on
patients across the post-marketing setting, Expanded Access Program
(EAP) and clinical trial participants.
To support the urgent need for treatment for the most severely
affected individuals living with SMA, Biogen initiated one of the
largest, global, pre-approval EAPs in any rare disease, providing
access to therapy free of charge. From its launch to June 30, 2018,
the EAP has provided treatment access to more than 750 patients
across 29 countries. Biogen also supports a Named Patient Sales
Program (NPP), which allows access to SPINRAZA in countries where
it is not commercially available.
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, the largest of its kind in
SMA, that moved SPINRAZA from its first dose in humans in 2011 to
its first regulatory approval in five years.
About SMA1-5 SMA is a rare, genetic,
neuromuscular disease that is characterized by loss of motor
neurons in the spinal cord and lower brain stem, resulting in
severe and progressive muscle atrophy and weakness. Ultimately,
individuals with SMA may lose the ability to walk and can have
difficulty performing the basic functions of life, such as
breathing and swallowing, which results in significant healthcare
intervention and caregiver assistance. Left untreated, the majority
of infants with the most severe form of the disease do not live to
see their second birthday without respiratory intervention.
Due to a deletion of, or mutation 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 an
individual has. 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), developed using
Ionis’ 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 a deficiency in SMN protein. 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 been shown to increase the amount of full-length SMN
protein in individuals with SMA.7
SPINRAZA must be administered via intrathecal injection, which
delivers therapies directly into the cerebrospinal fluid (CSF)
around the spinal cord,8 where motor neurons degenerate in
individuals with SMA due to insufficient levels of SMN
protein.9
In the clinical trial program, SPINRAZA demonstrated a favorable
benefit-risk profile. The most common adverse reactions that
occurred in the SPINRAZA group were 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 ASOs. Individuals may be
at increased risk of bleeding complications. Renal toxicity has
been observed after administration of some ASOs. SPINRAZA is
present in and excreted by the kidney.
Please click for Important Safety Information and full
Prescribing Information in the U.S. and Europe, or visit your
respective country’s product website.
About BiogenAt Biogen, our mission is clear: we
are pioneers in neuroscience. Biogen discovers, develops and
delivers worldwide innovative therapies for people living with
serious neurological and neurodegenerative diseases. One of the
world’s first global biotechnology companies, Biogen was founded in
1978 by Charles Weissmann, Heinz Schaller, Kenneth Murray and Nobel
Prize winners Walter Gilbert and Phillip Sharp, and today has the
leading portfolio of medicines to treat multiple sclerosis, has
introduced the first and only approved treatment for spinal
muscular atrophy and is focused on advancing neuroscience research
programs in Alzheimer’s disease and dementia, multiple sclerosis
and neuroimmunology, movement disorders, neuromuscular disorders,
pain, ophthalmology, neuropsychiatry and acute neurology. Biogen
also manufactures and commercializes biosimilars of advanced
biologics.
We routinely post information that may be important to investors
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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, about the potential benefits, safety and
efficacy of SPINRAZA; the results of certain real-world data; the
status of Biogen’s current regulatory filings; Biogen’s plans for
additional regulatory filings in other jurisdictions; availability
of patient access and reimbursement pathways, which may vary on a
country-by-country basis; the identification and treatment of SMA;
the potential of Biogen’s commercial business, including SPINRAZA;
and risks and uncertainties associated with drug development and
commercialization. These statements may be identified by words such
as “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,”
“forecast,” “goal,” “intend,” “may,” “plan,” “possible,”
“potential,” “will” and other words and terms of similar meaning.
Drug development and commercialization involve a high degree of
risk, and only a small number of research and development programs
result in commercialization of a product. Results in early stage
clinical trials may not be indicative of full results or results
from later stage or larger scale clinical trials and do not ensure
regulatory approval. You should not place undue reliance on these
statements or the scientific data presented.
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 the 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 and/or unexpected concerns that may arise from
additional data or analysis; ; regulatory authorities may require
additional information or further studies, or may fail or refuse to
approve or may delay approval of SPINRAZA or expansion of product
labeling; the occurrence of adverse safety events; risks of
unexpected costs or delays; we may encounter other unexpected
hurdles; failure to protect and enforce our data, intellectual
property and other proprietary rights and uncertainties relating to
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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 our most recent annual or
quarterly report and in other reports we have filed with the
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. Finkel R, Chiriboga C, Vajsar J, et al. Treatment of
infantile-onset spinal muscular atrophy with nusinersen: a phase 2,
open-label, dose-escalation study. Lancet.
2016;388(10063):3017-3026.
8. Evers MM, Toonen LJ, van Roon-Mom WM. Antisense
oligonucleotides in therapy for neurodegenerative disorders. Adv
Drug Deliv Rev. 2015;87:90-103.
9. Lunn MR, Wang CH. Spinal muscular atrophy. Lancet.
2008;371(9630):2120-2133.
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