- A statistically significant, 37.4%
difference (P=0.03), slowing of disease progression in
ALSFRS-R, in patients treated with PrimeC compared to placebo, in
the pre-specified Per Protocol (PP) population
analysis
- Neurofilament biomarker results from Biogen collaboration
expected in January 2024
- Primary biomarker endpoints, TDP-43 and Prostagladin2,
are expected in H1 2024
- PrimeC's meaningful effect magnitude, strong safety
profile, and unique mechanism of action will be discussed with the
FDA and other regulatory agencies in an End of Phase 2 meeting in
H1 2024
CAMBRIDGE, Mass., Dec. 14,
2023 /PRNewswire/ -- NeuroSense Therapeutics
Ltd. (Nasdaq: NRSN) ("NeuroSense"), a company developing treatments
for severe neurodegenerative diseases, today reported additional
positive efficacy data from further evaluation of its Phase
2b trial (PARADIGM) with NeuroSense's
lead drug candidate for amyotrophic lateral sclerosis ("ALS"),
PrimeC.
Evaluation of the pre-specified Per Protocol (PP) population
analysis of the recent top-line results from PARADIGM revealed
a statistically significant slowing of disease progression with a
37.4% (p=0.03) difference in the gold standard ALS tracking
measure, the ALS Functional Rating Scale-Revised ("ALSFRS-R"), in
favor of PrimeC vs placebo, and 17.2% (p=0.39) difference
in Slow Vital Capacity ("SVC"), in favor of PrimeC vs placebo.
The PP analysis population includes all participants who adhered to
the trial protocol and treatment plan without any major protocol
deviations. The goal of a PP analysis in clinical trials is to
assess the efficacy of a treatment under optimal conditions,
thereby providing a clearer understanding of how well the treatment
works when implemented as intended, contributing to a more
comprehensive view of the trial results. PARADIGM's PP
population analysis is pre-defined in the trial's statistical
analysis plan, which includes 62 patients (43 active and 19
placebo) compared to 68 patients in the Intent to Treat (ITT)
population (45 active and 23 placebo).
PARADIGM is a prospective, multinational,
randomized, double-blind, placebo-controlled Phase
2b (NCT05357950) clinical trial. The
trial's primary endpoints include: safety and tolerability, and
ALS-related biomarkers TDP-43 and Prostagladin2. The trial's
secondary endpoints include: clinical efficacy outcome measures,
ALSFRS-R and SVC. ALSFRS-R is the most widely used ALS tracking
tool accepted by the FDA, utilized by neurologists treating ALS
patients, in clinical trials, and by other regulators to determine
disease progression. It tracks 12 changes in a person's physical
abilities over time including functions such as: speech, walking,
climbing stairs, dressing/hygiene, handwriting, turning in bed,
cutting food, salivation, swallowing, and breathing. SVC is a
measurement of respiratory function.
While PARADIGM is powered to demonstrate statistically
significant changes in the trial's primary endpoints, the highly
favorable clinical results seen in the PP analysis achieved an
unexpected statistical significance.
The new data reported today comes on the heels of recent
positive top-line safety and efficacy data of PARADIGM announced by
NeuroSense. An analysis of the ITT top-line data from the 6-month
double-blind segment of the trial showed clinically meaningful
signs of efficacy with a 29% difference in ALSFRS-R (p=0.12) and a
13% difference in SVC (p=0.5), both in favor of PrimeC vs placebo.
These data include all 68 people living with ALS enrolled in
Canada, Italy, and Israel, with the exclusion of one patient who
was misdiagnosed. Most patients enrolled in both the active and
placebo arms of trial were concurrently treated with Riluzole, the
ALS standard of care medication, indicating PrimeC slowed disease
progression well beyond the level afforded by the FDA approved ALS
drug.
In addition, the trial met its primary endpoint of safety and
tolerability with results comparable to placebo, establishing a
solid safety profile for PrimeC. 96% of the trial participants who
completed the 6-month double-blind portion of the trial chose to
receive treatment with PrimeC through a 12-month open label
extension. Furthermore, to date, all participants that completed
the 18-month trial treatment duration requested to continue taking
PrimeC, which is provided to them via an Investigator Initiated
Trial.
NeuroSense expects to report results from a strategic
collaboration with Biogen in January
2024, evaluating the impact of PrimeC on neurofilament
levels in participants enrolled in PARADIGM. Upon receipt of
results, Biogen has the right of first refusal to co-develop/
commercialize PrimeC for the treatment of ALS for a limited
time following the results. The Company expects to report primary
biomarker endpoints of ALS hallmarks TDP-43 and Prostagladin2, to
evaluate PrimeC's biological activity and target engagement, in the
first half of 2024 following the completion of the analysis of
participants' plasma.
An End of Phase 2 meeting with the FDA and a Scientific Advice
meeting with European Medicines Agency (EMA) to discuss these
results and to determine the best path forward for PrimeC's
development is expected in the first half of 2024.
"As we analyze the PARADIGM trial results, we continue to gain a
better understanding of PrimeC's potential to render a significant
and meaningful clinical benefit to people living with ALS. Today we
are eager to share these new data with the ALS community, as we
believe the PP analysis, demonstrating a statistically significant
37.4% difference in ALSFRS-R in patients treated with PrimeC vs.
placebo, is an exceptional result," stated Alon Ben-Noon, NeuroSense's CEO. "This
data, in conjunction with hopefully correlative neurofilament
readouts, will create a regulatory opportunity to advance PrimeC's
development in a breakthrough manner toward the market."
About ALS
Amyotrophic lateral sclerosis ("ALS") is an incurable
neurodegenerative disease that causes complete paralysis and death
within 2-5 years from diagnosis. Every year, more than 5,000
patients are diagnosed with ALS in the U.S. alone, with an annual
disease burden of $1 billion. The number of patients with ALS
is expected to grow by 24% by 2040 in the U.S. and EU.
About PrimeC
PrimeC, NeuroSense's lead drug candidate, is a novel
extended-release oral formulation composed of a unique fixed-dose
combination of two FDA-approved drugs: ciprofloxacin and celecoxib.
PrimeC is designed to synergistically target several key mechanisms
of ALS that contribute to motor neuron degeneration, inflammation,
iron accumulation and impaired ribonucleic acid ("RNA") regulation
to potentially inhibit the progression of ALS. NeuroSense completed
the 6-month double-blind portion of its Phase 2b ALS clinical trial which met its safety and
tolerability endpoints, as well as showing a statistically
significant slowing of disease progression in the pre-specified Per
Protocol (PP) population. Additional data from the Phase
2b trial are expected H1 2024. PrimeC
was granted Orphan Drug Designation by the U.S. Food and Drug
Administration and the European Medicines Agency.
About NeuroSense
NeuroSense Therapeutics, Ltd. is a clinical-stage biotechnology
company focused on discovering and developing treatments for
patients suffering from debilitating neurodegenerative diseases.
NeuroSense believes that these diseases, which include amyotrophic
lateral sclerosis (ALS), Alzheimer's disease and Parkinson's
disease, among others, represent one of the most significant unmet
medical needs of our time, with limited effective therapeutic
options available for patients to date. Due to the complexity of
neurodegenerative diseases and based on strong scientific research
on a large panel of related biomarkers, NeuroSense's strategy is to
develop combined therapies targeting multiple pathways associated
with these diseases.
For additional information, we invite you to visit
our website and follow us
on LinkedIn and X (Twitter).
Forward-Looking Statements
This press release contains "forward-looking statements" that
are subject to substantial risks and uncertainties. All statements,
other than statements of historical fact, contained in this press
release are forward-looking statements. Forward-looking statements
contained in this press release may be identified by the use of
words such as "anticipate," "believe," "contemplate," "could,"
"estimate," "expect," "intend," "seek," "may," "might," "plan,"
"potential," "predict," "project," "target," "aim," "should,"
"will" "would," or the negative of these words or other similar
expressions, although not all forward-looking statements contain
these words. Forward-looking statements are based on NeuroSense
Therapeutics' current expectations and are subject to inherent
uncertainties, risks and assumptions that are difficult to predict
and include statements regarding PrimeC as a potential treatment
for people with ALS, the timing for release of additional results
from PARADIGM clinical trial, and other regulatory milestones, the
timing for release of results from the Company's strategic
collaboration with Biogen, the cash runway of the Company, the
timing of a Phase 2 trial for Alzheimer's disease and patient
enrollment regarding a Phase 3 pivotal ALS trial of PrimeC.
Further, certain forward-looking statements are based on
assumptions as to future events that may not prove to be accurate.
The future events and trends may not occur and actual results could
differ materially and adversely from those anticipated or implied
in the forward looking statements. These risks include unexpected
R&D costs or operating expenses, a delay in the reporting of
additional results from PARADIGM clinical trial, a delay in the
reporting of results from the Company's strategic collaboration
with Biogen, the timing of expected regulatory and business
milestones, risks associated with meeting with the FDA to determine
the best path forward following the results from PARADIGM clinical
trial, including a delay in any such meeting, a delay in patient
enrollment for a Phase 2 trial for Alzheimer's disease or its
planned Phase 3 pivotal ALS trial of PrimeC; the potential for
PrimeC to safely and effectively target ALS; preclinical and
clinical data for PrimeC; the uncertainty regarding outcomes and
the timing of current and future clinical trials; timing for
reporting data; the development and commercial potential of any
product candidates of the company; and other risks and
uncertainties set forth in NeuroSense's filings with the Securities
and Exchange Commission (SEC). You should not rely on these
statements as representing our views in the future. More
information about the risks and uncertainties affecting the Company
is contained under the heading "Risk Factors" in the Annual Report
on Form 20-F filed with the Securities and Exchange Commission on
March 22, 2023 and the Company's
subsequent filings with the SEC. Forward-looking statements
contained in this announcement are made as of this date, and
NeuroSense Therapeutics Ltd. undertakes no duty to update such
information except as required under applicable law.
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