Biogen Presents Data at 2019 AAN Annual Meeting Affirming
Longer-Term Safety and Durability of Treatment with SPINRAZA®
(nusinersen)
Biogen Inc. (Nasdaq: BIIB) today announced new data affirming the
safety and durability of SPINRAZA® (nusinersen) and highlighting
its clinically meaningful benefits for individuals with spinal
muscular atrophy (SMA). Data from the SHINE extension study, with
patients followed for up to four years, the NURTURE study of
pre-symptomatic infants and an evaluation of phosphorylated
neurofilament heavy chain (pNF-H) as a biomarker will be featured
presentations at the 71st annual meeting of the American Academy of
Neurology (AAN) in Philadelphia, PA (May 4-10, 2019).
“Each milestone in these studies marks a new chapter in what it
means to live with SMA, and the insight provided is invaluable in
understanding the long-term experience of this rare disease,” said
Alfred Sandrock, Jr., M.D., Ph.D., executive vice president and
chief medical officer at Biogen. “These results confirm previous
data from our trials, which demonstrated that early treatment with
SPINRAZA can make a critical difference in survival and achieving
motor milestones. The data also demonstrate that improvements in
motor milestones were achieved in individuals who began treatment
with SPINRAZA at a later age. This is a powerful development for
the SMA community.”
Watch this video with a story about the experience of a family
facing infantile-onset SMA, (most likely to develop SMA Type 1)
here: http://www.globenewswire.com/NewsRoom/AttachmentNg/b057996c-8146-4a1e-bdbf-06eccae12cc7
Interim results from the ENDEAR-SHINE open-label extension study
of infants (n=89) followed for up to four years demonstrated that
treatment with SPINRAZA resulted in additional or new motor
function improvements on the Children’s Hospital of Philadelphia
Infant Test of Neuromuscular Disorders (CHOP INTEND). The infants
also exhibited improved event-free survival rates compared to the
natural history of the disease. There were no new safety findings.
Additional highlights from ENDEAR-SHINE include:
- As of October 15, 2018, study participants who received
SPINRAZA in ENDEAR and SHINE (n=65) increased average CHOP INTEND
score by 16.8 points after nearly three years of treatment.
- Those in the sham-control arm in ENDEAR and that received
SPINRAZA in SHINE (n=24) increased average CHOP INTEND score by 8.2
points after over 1.5 years of treatment.
- Patients receiving SPINRAZA in ENDEAR and SHINE continued to
achieve motor milestones during SHINE. Both those who began
treatment younger (n=30, less than or equal to 5.42 months) and
older (n=21, greater than 5.42 months) demonstrated the ability to
sit without support, 60 and 38 percent respectively. At nearly
three years of follow-up, infants in the younger age group
demonstrated greater improvements in CHOP INTEND score (19.4 vs.
13.8 points).
- Patients treated with SPINRAZA in ENDEAR and SHINE demonstrated
a longer period of survival without need for permanent ventilation
(median 75.0 weeks). This compared to event-free survival among
patients initiating treatment in SHINE (median 22.6 weeks). Among
patients who received sham in ENDEAR and SPINRAZA in SHINE, the
median time of event-free survival was reached in ENDEAR while
untreated. Among infants who initiated treatment in SHINE and were
alive without permanent ventilation at baseline, 58 percent
remained alive without permanent ventilation at the data
cutoff.
Data from CHERISH-SHINE, which evaluated individuals with
later-onset SMA (n=125, most likely to develop SMA Type 2 or 3),
demonstrated that earlier treatment resulted in greater
improvements in motor function and continued improvement or
stabilization of motor function scores. Mean change in Hammersmith
Functional Motor Scale Expanded (HFSME) score was 3.7 for
participants treated with SPINRAZA in SHINE and CHERISH. This
compared to a positive 0.4 change from baseline among participants
in the CHERISH sham-control arm and who received SPINRAZA in SHINE.
During CHERISH, sham-control participants experienced a 0.4 decline
in HFSME. Four participants in the youngest age group in the study
(n=39, less than 3.69 years) were walking independently at Day 690
compared to no patients at baseline. There were no new safety
findings. Patients were followed for up to four years, adding to
the long-term safety profile of SPINRAZA.
Data from the NURTURE study showed that pre-symptomatic treatment
of infantile-onset SMA (n=25, most likely to develop SMA Type 1 or
2) resulted in motor milestone achievements more consistent with
normal motor development. Evaluations were conducted at a median
age of 26 months. All infants were able to sit without support and
88 percent could walk with assistance and 77 percent could walk
without assistance. All infants were alive and none required
permanent ventilation. No new safety concerns were identified. In
the natural history of SMA, individuals are unable to sit without
support (SMA Type 1) or walk (SMA Type 1 or 2) and often require
respiratory and nutritional interventions in order to live past the
age of two (SMA Type 1). The May 2018 data was previously
presented.
An evaluation of pNF-H in plasma highlighted its potential to
predict disease activity and suggested that it may be a useful
biomarker in SMA. Baseline measure of pNF-H was higher in
individuals with SMA (n=302) than those without SMA (n=34).
Individuals from the NURTURE, ENDEAR and CHERISH studies treated
with SPINRAZA experienced rapid pNF-H declines followed by
stabilization at lower levels. The results are part of ongoing work
to identify biomarkers that could provide insight on disease
progression in SMA. {Encore presentation}.
The pNF-H and NURTURE presentations were selected by AAN from
more than 3,000 other presentations as abstracts of distinction for
their scientific merit.
About SPINRAZA® (nusinersen)1-4SPINRAZA is the
first and only approved medicine for the treatment of spinal
muscular atrophy (SMA) and is currently available in more than 40
countries. As of March 31, 2019, more than 7,500 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.
SPINRAZA is an antisense oligonucleotide (ASO) developed using
Ionis’ proprietary antisense technology that is designed to treat
the root cause of SMA. SPINRAZA alters the splicing of SMN2
pre-mRNA in order to increase production of full-length SMN
protein. 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.
SPINRAZA is administered via intrathecal injection, which delivers
therapies directly into the cerebrospinal fluid (CSF) around the
spinal cord, where motor neurons degenerate in individuals with SMA
due to insufficient levels of SMN protein.
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.
Biogen licensed the global rights to develop, manufacture and
commercialize SPINRAZA from Ionis Pharmaceuticals, Inc. (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 the SPINRAZA Clinical Program NURTURE is
an ongoing, open-label study of infants up to six weeks of age at
time of first dose, who were genetically diagnosed with SMA and had
not experienced any symptoms by the time of first dose. Data
presented at the World Muscle Society in October 2018 demonstrated
unprecedented efficacy in treating patients pre-symptomatically. In
that analysis, all NURTURE study participants were alive and did
not require permanent ventilation, in contrast to natural history
of SMA. Study participants achieved motor milestones with 100
percent sitting independently and 88 percent able to walk. 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 most 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 are most likely to 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.
The ENDEAR study was a thirteen-month, international, phase 3,
multicenter, double-blind, sham-controlled study of 121 patients
with infantile-onset SMA (most likely to develop Type 1). Results
from the pivotal study, which were published in the New England
Journal of Medicine, evaluated the efficacy and safety in patients
that onset of signs and symptoms of SMA before six months of age.
Patients treated with SPINRAZA in the ENDEAR study achieved
clinically meaningful improvement in achievement of motor
milestones compared to untreated study participants with 51 percent
vs. 0 percent demonstrating Hammersmith Infant Neurological
Examination section 2 (HINE-2) motor milestone response, an
assessment which evaluates eight motor-milestone categories, based
on the defined criteria.
CHERISH was a fifteen-month, phase 3, randomized, double-blind,
sham-controlled study investigating SPINRAZA in 126 non-ambulatory
patients with later-onset SMA (most likely to develop SMA Type 2 or
3). Patients included had onset of signs and symptoms at greater
than 6 months of age, and an age of 2 to 12 years at screening. The
final analysis of CHERISH data found that children receiving
SPINRAZA experienced a highly statistically significant and
clinically meaningful improvement in motor function compared to
those who did not receive treatment with a treatment difference of
4.9 points on the Hammersmith Functional Motor Scale Expanded.
SPINRAZA demonstrated a favorable benefit-risk profile in the
study.
About SMA2,5 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. About 1 in
10,000 live births have a diagnosis of SMA. Ultimately, individuals
with SMA can lose the ability to walk and 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 (Type 1) do not live
beyond their second birthday without respiratory intervention.
People with childhood or adult onset SMA (Type 2 or 3) produce
greater amounts of SMN protein resulting in less severe, but still
life-altering forms of the disease.
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 typically
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 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 as well as
related therapeutic adjacencies. 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 MS
and neuroimmunology, Alzheimer’s disease and dementia, movement
disorders, neuromuscular disorders, acute neurology, neurocognitive
disorders, pain, and ophthalmology. Biogen also commercializes
biosimilars of advanced biologics.
We routinely post information that may be important to investors
on our website at www.biogen.com. To learn more, please
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Biogen Safe Harbor This news 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;
and the identification and treatment of SMA. These statements may
be identified by words such as “aim,” “anticipate,” “believe,”
“could,” “estimate,” “expect,” “forecast,” “goal,” “intend,” “may,”
“plan,” “possible,” “potential,” “will,” “would” 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 the occurrence of
adverse safety events and/or unexpected concerns that may arise
from additional data or analysis; risks of unexpected costs or
delays; failure to protect and enforce our data, intellectual
property and other proprietary rights and uncertainties relating to
intellectual property claims and challenges; product liability
claims; and 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 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 news 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.
Reference: 1. 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.
2. 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.
3. Evers MM, Toonen LJ, van Roon-Mom WM. Antisense
oligonucleotides in therapy for neurodegenerative disorders. Adv
Drug Deliv Rev. 2015;87:90-103.
4. Lunn MR, Wang CH. Spinal muscular atrophy. Lancet.
2008;371(9630):2120-2133.
5. 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.
MEDIA CONTACT: David Caouette+617 679
4945public.affairs@biogen.com |
INVESTOR CONTACT: Matt Calistri+1 781 464
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