Biogen Inc. (Nasdaq: BIIB) today announced detailed results from
Part B and Part C of the Phase 2/3 DEVOTE study evaluating the
safety and efficacy of an investigational higher dose regimen of
nusinersen in spinal muscular atrophy (SMA), showing benefits in
both individuals previously treated and treatment-naïve to
nusinersen with infantile-onset or later-onset SMA. The
investigational, higher dose regimen of nusinersen comprises a more
rapid loading regimen, two 50 mg doses 14 days apart, and higher
maintenance regimen, 28 mg, every 4 months, compared to the
approved nusinersen regimen (SPINRAZA®). Data to be presented
during the World Muscle Society (WMS) 2024 Congress (Oct. 8-12,
2024 in Prague) highlight the potential of this investigational
higher dose regimen to help address remaining unmet need in SMA.
“Strikingly, the higher dose regimen lowered neurofilament more
quickly, telling us that it’s more rapidly slowing
neurodegeneration. We know how critical this is in people living
with SMA. Over time, we see evidence of the benefit of the higher
dose regimen across SMA phenotypes,” said Thomas Crawford, M.D.,
co-director, Muscular Dystrophy Association Clinic at Johns Hopkins
Medicine. “Despite administering much more drug, the higher dose
regimen appears to have a consistent safety profile with the
approved 12 mg regimen.”
DEVOTE is a three-part study that enrolled 145 participants
across ages and SMA types. The pivotal Part B cohort (n=75)
met its primary endpoint where treatment-naïve, symptomatic infants
who received the higher dose regimen saw significantly greater
improvements in motor function as measured by Children’s Hospital
of Philadelphia Infant Test of Neuromuscular Disorders
(CHOP-INTEND) compared to a prespecified matched sham (untreated)
group from the Phase 3 ENDEAR study (+15.1 vs -11.1,
p<0.0001).
In addition to the primary comparisons of the higher dose
regimen to the matched sham group, analyses comparing to the
approved 12 mg regimen were also performed, though not adequately
powered to detect significant differences between these groups.
Despite the relatively small study size, secondary analyses
consistently favored the higher dose group in all comparisons to
sham and nearly all comparisons to the 12 mg regimen. Detailed
results include:
- The higher dose regimen led to a
94% reduction in plasma neurofilament light chain (NfL), a marker
of neurodegeneration, from baseline to Day 183, compared to a 30%
reduction in the sham control group (p<0.0001). Additionally,
more rapid NfL reductions were observed with the higher dose
regimen, with greater reductions observed at Day 64 (nominal
p=0.0050) as compared to the 12 mg regimen.
- At Day 302, the higher dose regimen showed a 19.6 point
improvement from baseline on CHOP-INTEND compared to 21.6 point
improvement with the 12 mg regimen (least-squares mean difference
of -1.94; p=0.8484). At Day 302, the higher dose regimen showed a
mean improvement in change in Hammersmith Infant Neurological Exam
section 2 (HINE-2) compared to the 12 mg regimen (least-squares
mean difference: 0.58; p=0.1734).
- The higher dose regimen reduced the risk of death or permanent
ventilation by 67.8% relative to sham (HR: 0.322; nominal p=0.0006)
and 29.9% relative to the 12 mg regimen (HR: 0.701; p=0.2775). A
similar pattern was observed for overall survival, as well as other
relevant events such as hospitalizations and serious respiratory
events.
- Separately, in the Part B later-onset cohort, participants
receiving the higher dose regimen (n=16) achieved numerically
greater improvements on motor function assessments including the
Hammersmith Functional Motor Scale – Expanded (HFMSE) and the
Revised Upper Limb Module (RULM) at Day 302 over the 12 mg group
(n=8) in DEVOTE, and at Day 279 as compared to pre-specified
matched 12 mg (n=32) and sham control groups (n=16) from
CHERISH.
Initial results were also presented from Part C (n=40) of
DEVOTE, in which a diverse group of participants, age 4-65,
transitioned to the higher dose regimen (one 50 mg dose followed by
the 28 mg maintenance regimen) after a median of 3.9 years on the
approved 12 mg regimen. Participants experienced improvements in
motor function after transitioning with mean increases of 1.8
points on HFMSE and 1.2 points on RULM from baseline at Day
302.
Across parts of DEVOTE, the higher dose regimen was generally
well tolerated and showed a safety profile similar to that of the
approved 12 mg regimen. In the 12 mg regimen the most common
adverse events (AEs) were respiratory infection, fever,
constipation, headache, vomiting and back pain. The frequency of
AEs in DEVOTE was similar across the nusinersen treatment arms. The
number of AEs leading to study withdrawal and death only occurred
in the Part B treatment-naive cohort and were 20% (10), 24% (6) and
55% (11), in the 50/28 mg, 12 mg and matched sham arms,
respectively.
“While we’ve seen great progress over the past decade in
improving the lives of those with SMA, gaps remain and we can do
more to address the full range of unmet needs and goals within our
community,” said Kenneth Hobby, President of Cure SMA. “The DEVOTE
study’s findings are promising and show the potential for
additional meaningful advancements that could further enhance motor
function which impacts daily living activities for all people
living with SMA.”
Biogen plans to file applications for the 50/28 mg higher dose
nusinersen regimen with global regulatory agencies. Nusinersen is
currently commercialized under the brand name SPINRAZA in over
71 countries at the label-approved dose of 12 mg.
About the DEVOTE StudyDEVOTE was a Phase 2/3
randomized, controlled, dose-escalating study designed to evaluate
the safety, tolerability, pharmacokinetics and potential for even
greater efficacy of nusinersen when administered at a higher dose
(50/28 mg) than the currently approved regimen (12 mg) for the
treatment of spinal muscular atrophy (SMA). The study enrolled 145
participants across ages and SMA types at approximately 42 sites
around the world. DEVOTE includes an open-label safety evaluation
cohort (Part A), a double-blind, active control randomized
treatment cohort (Part B), followed by an open-label treatment
cohort (Part C) to assess the safety and tolerability of
transitioning participants from the currently approved dose of
SPINRAZA to the higher dose being tested in the study.
Part B is comprised of an infantile-onset cohort (n=75), which
is considered pivotal, and a later-onset cohort. The primary
endpoint of Part B measured the change from baseline on CHOP-INTEND
at six months comparing the higher dose regimen of nusinersen to a
matched, untreated sham control group from the Phase 3 ENDEAR
study. ENDEAR is one of the two pivotal studies that formed the
basis of regulatory approval for SPINRAZA® 12 mg.
Part C is an open-label evaluation of the higher dose regimen in
children and adults who transitioned from SPINRAZA 12 mg to the
50/28 mg regimen (n=40).
More information about the DEVOTE study (NCT04089566) is
available at clinicaltrials.gov.
About SPINRAZASPINRAZA is approved in more than
71 countries to treat infants, children and adults with spinal
muscular atrophy (SMA). As a foundation of care in SMA, more than
14,000 individuals have been treated with SPINRAZA
worldwide.1
SPINRAZA is an antisense oligonucleotide (ASO) that targets the
underlying cause of motor neuron loss by continuously increasing
the amount of full-length survival motor neuron (SMN) protein
produced in the body.2 It is administered directly into the
central nervous system, where motor neurons reside, to deliver
treatment where the disease starts.2
SPINRAZA has shown sustained efficacy across ages and SMA types
with a well-established safety profile based on data in patients
treated up to 10 years,3,4 combined with unsurpassed
real-world experience. The nusinersen clinical development program
encompasses more than 10 clinical studies, which have included more
than 460 individuals across a broad spectrum of patient
populations, including two randomized controlled studies
(ENDEAR and CHERISH). The NURTURE open-label extension study is
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). 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 BiogenFounded in 1978, Biogen is a
leading biotechnology company that pioneers innovative science to
deliver new medicines to transform patients’ lives and to create
value for shareholders and our communities. We apply deep
understanding of human biology and leverage different modalities to
advance first-in-class treatments or therapies that deliver
superior outcomes. Our approach is to take bold risks, balanced
with return on investment to deliver long-term growth.
We routinely post information that may be important to investors
on our website at www.biogen.com. Follow us on social
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Biogen Safe HarborThis news release contains
forward-looking statements, including related to the potential
clinical effects of SPINRAZA; the potential benefits, safety and
efficacy of SPINRAZA; the clinical development program for
SPINRAZA; the identification and treatment of SMA; our research and
development program for the treatment of SMA; the potential of our
commercial business and pipeline programs, including SPINRAZA; and
risks and uncertainties associated with drug development and
commercialization. These forward-looking statements may be
accompanied by words such as “aim,” “anticipate,” “believe,”
“could,” “estimate,” “expect,” “forecast,” “intend,” “may,” “plan,”
“potential,” “possible,” “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 our forward-looking statements.
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 development and potential commercialization of
SPINRAZA; the risk that we may not fully enroll our clinical trials
or enrollment will take longer than expected; unexpected concerns
may arise from additional data, analysis or results obtained during
our clinical trials; regulatory authorities may require additional
information or further studies, or may fail or refuse to approve or
may delay approval of our drug candidates, including SPINRAZA; the
occurrence of adverse safety events; the risks of unexpected
hurdles, 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; 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 speak only as of the date of this news
release.
We do not undertake any obligation to publicly update any
forward-looking statements.
References:
- Based on commercial patients, early
access patients, and clinical trial participants through December
31, 2022.
- SPINRAZA U.S. Prescribing
Information. Available
at:https://www.spinraza.com/content/dam/commercial/specialty/spinraza/caregiver/en_us/pdf/spinraza-prescribing-information.pdf.
Accessed: September 2024.
- Core Data sheet, Version 13,
October 2021. SPINRAZA. Biogen Inc, Cambridge, MA.
- Finkle et al. Cure SMA 2024. “Final
Safety and Efficacy Data From the SHINE Study in Participants With
Infantile-Onset and Later-Onset SMA.”
MEDIA CONTACT:BiogenJack Cox+1
781-464-3260public.affairs@biogen.com |
INVESTOR CONTACT:BiogenStephen
Amato+1 781-464-2442IR@biogen.com |
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