Biogen Inc. (Nasdaq: BIIB) today announced plans to initiate a
global Phase 3b clinical study, ASCEND. The ASCEND study is
designed to evaluate the clinical outcomes and assess the safety of
a higher dose of nusinersen* in children, teens and adults with
later-onset spinal muscular atrophy (SMA) following treatment with
Evrysdi® (risdiplam).
People with SMA do not produce enough survival motor neuron
(SMN) protein, which is critical for the ongoing maintenance of
motor neurons that support sitting, standing and movement. Over
time, people with SMA may lose their ability to perform everyday
activities, including brushing their teeth, turning on a light
switch or drinking from a cup.4,5 The goal of treatment in SMA is
to sufficiently protect motor neurons and help preserve
function.
“We believe that lower drug exposure may be contributing to
less-than-optimal treatment outcomes for some patients treated with
Evrysdi. The ASCEND study seeks to understand if nusinersen may
address that unmet medical need and will help inform the future of
SMA treatment, with the hope of improving patients’ outcomes for
the long term,” said Maha Radhakrishnan, M.D., Chief Medical
Officer at Biogen.
Available data suggest that exposure to Evrysdi diminishes with
increased age and weight, with an approximately 40 percent
reduction in drug concentration in adults compared to infants.6,7
Evrysdi’s dosing is capped at 5 milligrams (mg) once patients reach
20 kilograms (kg).8
At the approved 12-mg dose, motor neuron exposure to nusinersen
remains similar as patients age and grow.9 Further, nusinersen has
demonstrated proven, sustained efficacy and a well-characterized
safety profile, with long-term data in patients treated for more
than 7 years across ages and SMA types. Taken together, these data
support further exploration of whether a higher dose can deliver
even greater efficacy to patients. The ASCEND study will assess if
nusinersen at a higher dose may address outstanding clinical needs
among later-onset SMA patients treated with Evrysdi who want to
make a change in their treatment regimen. The same investigational
higher dose of nusinersen is also being evaluated in the
ongoing DEVOTE study.
“There have been significant advances in SMA treatment; however,
there is still no cure and unmet medical needs remain,” said
Professor Tim Hagenacker, Head of Neuromuscular Diseases Unit,
Essen University in Germany, and a member of the ASCEND study
steering committee. “As part of my clinical practice, we’ve
observed an opportunity to potentially further improve patient
outcomes. With a higher dose of nusinersen, we are positioned to
explore what may be possible.”
The ASCEND protocol has been submitted to the U.S. Food and Drug
Administration and is planned to be an approximately 2.5-year study
projected to enroll up to 135 later-onset, non-ambulatory
individuals with SMA (aged 5 to 39). All participants must have
been previously treated with Evrysdi at the maximum recommended
dose of 5 mg and be willing and able to change their treatment
regimen to a higher dose of nusinersen. Participants must also fall
within a particular Revised Upper Limb Module (RULM) measurement
range to enter the study. Individuals enrolled in ASCEND will
receive two loading doses of nusinersen 50 mg two weeks apart,
followed by a maintenance dose of 28 mg every four months during
the study period. Efficacy is planned to be assessed by RULM.
Additional clinical outcomes include safety, Hammersmith Functional
Motor Scale Expanded (HFMSE) and caregiver burden. The study will
also evaluate upper limb fine motor function in participants aged
13 and older using the mobile application Konectom™, and
neurofilament levels as a marker of biological disease activity,
both exploratory endpoints.
The study aims to include children, teens and adults naïve to
treatment with nusinersen, as well as adults who were previously
treated with nusinersen prior to Evrysdi. The company aims for the
first eligible patients to be enrolled in 2021.
In addition to ASCEND, as a leader in SMA Biogen supports over
15 SMA disease registries with more than 4,000 patients across the
globe, which will help support treatment decisions within the
context of currently approved therapies, including the 12-mg dose
of nusinersen.
*Nusinersen is currently commercialized under the brand name
SPINRAZA®, and the U.S. Food and Drug Administration-approved dose
is 12 mg.
About
SPINRAZA® (nusinersen)The
SPINRAZA clinical development program encompasses 10 clinical
studies, which have included more than 300 individuals across a
broad spectrum of patient populations,10 including two
randomized controlled studies (ENDEAR and CHERISH). The ongoing
SHINE and NURTURE open-label extension studies are evaluating the
long-term impact of SPINRAZA. The most common adverse events
observed in clinical studies were respiratory infection, fever,
constipation, headache, vomiting and back pain. Laboratory tests
can monitor for renal toxicity and coagulation abnormalities,
including acute severe low platelet counts, which have been
observed after administration of some ASOs.
Biogen licensed the global rights to develop, manufacture and
commercialize SPINRAZA from Ionis Pharmaceuticals, Inc. (Nasdaq:
IONS), the leader in antisense therapeutics. Please click here
for Important Safety Information and full
Prescribing Information for SPINRAZA in the U.S., or visit
your respective country’s product website.
About Spinal Muscular Atrophy (SMA)SMA is a
rare, genetic, neuromuscular disease that affects individuals of
all ages. It is characterized by a loss of motor neurons in the
spinal cord and lower brain stem, resulting in progressive muscle
atrophy and weakness.11 SMA is caused by a deficiency in the
production of survival motor neuron (SMN) protein due to a damaged
or missing SMN1 gene, with a spectrum of disease
severity.11 Some individuals with SMA may never sit; some sit
but never walk; and some walk but may lose that ability over
time.12 In the absence of treatment, children with the most
severe form of SMA would not be expected to reach their second
birthday.11
SMA impacts approximately 1 in 11,000 live births,13 is a
leading cause of genetic death among infants13 and causes a
range of disability in teenagers and adults.12
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. Today Biogen has the leading
portfolio of medicines to treat multiple sclerosis, has introduced
the first approved treatment for spinal muscular atrophy,
commercializes biosimilars of advanced biologics and is focused on
advancing research programs in multiple sclerosis and
neuroimmunology, Alzheimer’s disease and dementia, neuromuscular
disorders, movement disorders, ophthalmology, neuropsychiatry,
immunology, acute neurology and neuropathic pain.
We routinely post information that may be important to investors
on our website at www.biogen.com. Follow us on social media –
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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 nusinersen; the results of certain real-world data;
the identification and treatment of SMA; our research and
development program for the identification and treatment of SMA;
the clinical development program for nusinersen, including the
study protocol and enrollment of the ASCEND study and the timing
thereof; 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,” “would” and other words
and terms of similar meaning. 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 risks relating to the
occurrence of adverse safety events and/or unexpected concerns that
may arise from additional data or analysis, including from the
planned ASCEND study; the risk that we may not fully enroll our
clinical trials, including the planned ASCEND study, or enrollment
will take longer than expected; failure to obtain regulatory
approvals in other jurisdictions; 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; regulatory authorities
may require additional information or further studies; product
liability claims; third party collaboration risks; and the direct
and indirect impacts of the ongoing COVID-19 pandemic on our
business, results of operations and financial condition. 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 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 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.
References:
- Mercuri E. et al. SUNFISH Part 2: Efficacy and safety of
risdiplam (RG7916) in patients with Type 2 or non-ambulant Type 3
spinal muscular atrophy (SMA). SMA Europe Feb 5-7, 2020
presentation.
- Evrysdi US FDA Summary Basis of Approval (SBA) documents.
Clinical Review(s): Page 67, table 15. Available at:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000TOC.cfm.
Accessed: September 2021.
- European Medicines Agency: EMA/216061/2021 – Evrysdi EPAR. Page
195, table 41. Available at:
https://www.ema.europa.eu/en/documents/assessment-report/evrysdi-epar-public-assessment-report_en.pdf.
Accessed September 2021.
- Rouault F, et al. Disease impact on general well-being and
therapeutic expectations of European Type II and Type III spinal
muscular atrophy patients. Neuromuscul Disord. 2017
May;27(5):428-438. doi: 10.1016/j.nmd.2017.01.018. Epub 2017 Feb
3.
- Mazzone ES, et al. Revised upper limb module for spinal
muscular atrophy: Development of a new module. Muscle Nerve. 2017
Jun;55(6):869-874. doi: 10.1002/mus.25430. Epub 2017 Feb 6.
- Evrysdi US FDA SBA documents. Clinical Pharmacology Review(s):
Page 41, table 18. The approximately 40% reduction is the
percentage difference between risdiplam observed exposures in the
youngest infants and adults. Available at:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000TOC.cfm.
Accessed: September 2021.
- European Medicines Agency: EMA/216061/2021 – Evrysdi EPAR. Page
71, figure 13. The approximately 40% reduction is the percentage
difference between risdiplam observed exposures in the youngest
infants and adults. Available at:
https://www.ema.europa.eu/en/documents/assessment-report/evrysdi-epar-public-assessment-report_en.pdf.
Accessed September 2021.
- Evrysdi U.S. Prescribing Information. Available at:
https://www.gene.com/download/pdf/evrysdi_prescribing.pdf.
Accessed: September 2021.
- Finkel RS, et al. Scientific Rationale for a Higher Dose of
Nusinersen. Cure SMA Virtual Research and Clinical Care Meeting
June 9–11, 2021 poster presentation.
- Core Data Sheet, Version 9, January 2019. SPINRAZA. Biogen Inc,
Cambridge, MA.
- National Institute of Neurological Disorders and Stroke, NIH.
Spinal Muscular Atrophy Fact Sheet. Available
at https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Spinal-Muscular-Atrophy-Fact-Sheet.
Accessed: September 2021.
- Wadman RI, Wijngaarde CA, Stam M, et al. Muscle strength and
motor function throughout life in a cross-sectional cohort of 180
patients with spinal muscular atrophy types 1c–4. Eur J Neurol.
2018;25(3):512-518.
- Cure SMA. About SMA. Available
at https://www.curesma.org/about-sma/. Accessed: September
2021.
MEDIA CONTACT:Allison Parks+1 781 464
3260public.affairs@biogen.com |
INVESTOR CONTACT:Mike Hencke+1 781 464 2442IR@biogen.com |
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