The New England Journal of Medicine Publishes SPINRAZA® (nusinersen) Phase 3 Study Results in Individuals with Later-Onset Spinal Muscular Atrophy

  • SPINRAZA demonstrated stabilization or improvement in motor function
    in individuals with spinal muscular atrophy (SMA) where the natural
    history of the disease is a decline in motor function over time
  • The majority of individuals treated with SPINRAZA demonstrated
    benefits in upper limb and general motor function, including crawling
    and standing with support
  • The overall findings continue to support the robust efficacy and
    favorable safety profile of SPINRAZA, the only approved treatment for
    SMA, across a broad patient population

(Nasdaq: BIIB) and Ionis
Pharmaceuticals, Inc.
(Nasdaq: IONS) announced end of study results
from CHERISH, the Phase 3 study evaluating SPINRAZA®
(nusinersen) for the treatment of individuals with later-onset spinal
muscular atrophy (SMA), were published today in The New England
Journal of Medicine
. The full manuscript titled, “Nusinersen Versus
Sham Control in Later-Onset Spinal Muscular Atrophy,” appears in the
February 15 issue of The
New England Journal of Medicine

The publication of CHERISH study results in The New England Journal
of Medicine
emphasizes SPINRAZA’s meaningful motor function and
upper limb improvements in individuals with later-onset SMA rarely seen
in the natural course of the disease, which is typically a continued
decline in motor function over time,” said Eugenio Mercuri, M.D., lead
study investigator, U.O.C. Neuropsichiatria Infantile – Policlinico
Universitario “A. Gemelli,” Rome, Italy. “During the study, some
individuals treated with SPINRAZA achieved motor milestones including
crawling or standing with assistance, or saw a stabilization or slowing
of disease progression. We also saw an improvement in upper limb
function, including raising objects.”

The pre-specified CHERISH primary endpoint was improvement in motor
function, as defined by change from baseline in the Hammersmith
Functional Motor Scale-Expanded (HFMSE). The HFMSE is a validated tool
specifically designed to assess motor function in individuals with SMA.
The final analysis demonstrated a highly statistically significant and
clinically meaningful improvement in motor function in individuals
treated with SPINRAZA versus the sham control, as observed by the
treatment difference of 4.9 points in the mean change from baseline to
Month 15 in the HFMSE score (p=0.0000001). When measuring changes from
baseline, individuals who received SPINRAZA (n=84) achieved a 3.9 point
mean improvement at Month 15, while individuals who were not on
treatment (n=42) experienced a mean decline of 1.0 point. Primary
endpoint results of the end of study analysis were consistent with the
interim analysis.

As the first and only approved treatment for SMA, the data published in
The New England Journal of Medicine continue to underscore the
benefit of SPINRAZA for individuals with later-onset SMA,” said Alfred
Sandrock, M.D., Ph.D., executive vice president and chief medical
officer at Biogen. “The CHERISH data are part of the largest clinical
development program to date for the treatment of SMA. The program in its
entirety shows that SPINRAZA has the potential to positively impact the
motor function of children with SMA regardless of their age or stage of
the disease.”

Data from the other endpoints analyzed, including attainment of new
motor milestones and upper limb motor function, were consistently in
favor of individuals who received treatment and were considered
clinically significant. Upper limb function, as measured by the Revised
Upper Limb Module (RULM), improved in individuals treated with SPINRAZA
(4.2 points) from baseline to Month 15 compared to untreated individuals
(0.5 points). The RULM is an important measure of motor function in
non-ambulatory individuals.

SPINRAZA demonstrated a favorable benefit-risk profile. Safety data were
consistent with those expected in the general SMA later-onset population
and in individuals undergoing lumbar puncture and were similar to those
reported in an open-label study in later-onset SMA.

The CHERISH data published today together with the results from the
Phase 3 ENDEAR study in individuals with infantile-onset SMA, which were
published last November in The New England Journal of Medicine,
emphasizes the therapeutic potential of SPINRAZA in individuals with
SMA,” said C. Frank Bennett, Ph.D., senior vice president of research
and leader of the neurological disease franchise at Ionis. “We believe
the fact that both SPINRAZA pivotal studies have been published in a
prestigious journal is a testament to the robustness of our SMA clinical
development program.”

Following the positive interim analysis, Biogen ended the CHERISH study
early so all participants could have the option to receive SPINRAZA in
the SHINE open-label extension study. In addition to SHINE, Biogen
continues to collect and evaluate data to provide a deeper understanding
of the efficacy and safety of SPINRAZA across SMA populations. The
SPINRAZA clinical development program includes more than five years of
data and is the largest body of evidence for an interventional approach
in SMA.

End of study results from ENDEAR, the Phase 3 SPINRAZAstudy
for the treatment of infantile-onset SMA, were published in the November
2, 2017 issue of The
New England Journal of Medicine

For more information about SPINRAZA and prescribing information in the
United States, please visit
Prescribing information in the European Union is available at


CHERISH is a Phase 3, multicenter, randomized, double-blind,
sham-procedure controlled study to assess the efficacy and safety of
SPINRAZA in individuals with later-onset SMA. The 15-month study
investigated SPINRAZA in 126 non-ambulatory individuals 2 to 12 years
old who experienced symptom onset at greater than 6 months of age. The
CHERISH primary efficacy endpoint measured improvement in motor
function, as defined by change from baseline in the Hammersmith
Functional Motor Scale-Expanded (HFMSE).

SPINRAZA Program Status

SPINRAZA is the first and only approved medicine for the treatment of
SMA and is currently approved in the United States, the European Union,
Brazil, Japan, Switzerland, Australia, South Korea, and Canada. Biogen
has submitted regulatory filings in additional countries and plans to
initiate additional filings in other countries.

Globally, starting 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, 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

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), 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 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 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 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.

About Biogen

At 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.
Founded in 1978 as one of the world’s first global biotechnology
companies by Charles Weissman, Heinz Schaller, Kenneth Murray and Nobel
Prize winners Walter Gilbert and Phillip Sharp, today Biogen 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 on our
website at To
learn more, please visit
and follow us on social media – Twitter,
LinkedIn, Facebook,

About Ionis Pharmaceuticals, Inc.

Ionis is the leading company in RNA-targeted drug discovery and
development focused on developing drugs for patients who have the
highest unmet medical needs, such as those patients with severe and rare
diseases. Using its proprietary antisense technology, Ionis has created
a large pipeline of first-in-class or best-in-class drugs, with over
three dozen drugs in development.

SPINRAZA® (nusinersen) has been approved in global markets
for the treatment of spinal muscular atrophy (SMA). Biogen is
responsible for commercializing SPINRAZA. Drugs that have successfully
completed Phase 3 studies include inotersen, an antisense drug Ionis is
developing to treat patients with hereditary TTR amyloidosis (hATTR),
and volanesorsen, an antisense drug discovered by Ionis and co-developed
by Ionis and Akcea Therapeutics to treat patients with either familial
chylomicronemia syndrome or familial partial lipodystrophy. Akcea, an
affiliate of Ionis, is a biopharmaceutical company focused on developing
and commercializing drugs to treat patients with serious cardiometabolic
diseases caused by lipid disorders. If approved, volanesorsen will be
commercialized through Ionis’ affiliate, Akcea. Volanesorsen filings for
marketing approval have been submitted in the U.S., EU and Canada.
Inotersen is progressing toward regulatory filings for marketing
authorization. Ionis’ patents provide strong and extensive protection
for its drugs and technology. Additional information about Ionis is
available at

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 Biogen’s current regulatory filings,
Biogen’s plans for additional regulatory filings in other jurisdictions,
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. Drug
development and commercialization involve a high degree of risk. 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 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 to approve or may delay approval of
Biogen’s drug candidates or expansion of product labeling; 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, or 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 Biogen’s 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 Biogen’s current
beliefs and expectations and speak only as of the date of this press
release. Biogen does not undertake any obligation to publicly update any
forward-looking statements, whether as a result of new information,
future developments, or otherwise.

Ionis Pharmaceuticals’ Forward-Looking Statement

This press release includes forward-looking statements regarding Ionis’
strategic relationship with Biogen and the development, activity,
therapeutic potential, safety and commercialization of SPINRAZA. Any
statement describing Ionis’ goals, expectations, financial or other
projections, intentions or beliefs is a forward-looking statement and
should be considered an at-risk statement. Such statements are subject
to certain risks and uncertainties, particularly those inherent in the
process of discovering, developing and commercializing drugs that are
safe and effective for use as human therapeutics, and in the endeavor of
building a business around such drugs. Ionis’ forward-looking statements
also involve assumptions that, if they never materialize or prove
correct, could cause its results to differ materially from those
expressed or implied by such forward-looking statements. Although Ionis’
forward-looking statements reflect the good faith judgment of its
management, these statements are based only on facts and factors
currently known by Ionis. As a result, you are cautioned not to rely on
these forward-looking statements. These and other risks concerning
Ionis’ programs are described in additional detail in Ionis’ annual
report on Form 10-K for the year ended December 31, 2016, and its most
recent quarterly report on Form 10-Q, which are on file with the SEC.
Copies of these and other documents are available from Ionis.

Ionis Pharmaceuticals™ is a trademark of Ionis Pharmaceuticals, Inc.
Akcea Therapeutics™ is a trademark of Ionis Pharmaceuticals, Inc.
SPINRAZA® is a registered trademark of Biogen.

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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.

3. Mailman MD, Heinz JW, Papp AC, et al. Molecular analysis of spinal
muscular atrophy and modification of the phenotype by SMN2. Genet Med.

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

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
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