With incorporation of key learnings, Phase
2b has >95% (approaching 100%)
statistical power to meet its primary endpoint: change
in Clinical Dementia Rating Sum-of-Boxes (CDR-SB) vs.
placebo
New data included in the presentation show
that in patients without Alzheimer's-related co-pathology,
neflamapimod treatment demonstrates significant reduction vs.
placebo of a potential blood biomarker of dementia with Lewy
bodies
BOSTON, Oct. 25,
2023 /PRNewswire/ -- CervoMed Inc. (NASDAQ: CRVO), a
clinical-stage company focused on developing treatments for
degenerative diseases of the brain, announced an oral presentation
today by Dr. Niels Prins, Chief
Executive Officer of the Brain Research Center in the Netherlands, at the 16th
Clinical Trials in Alzheimer's Disease (CTAD) conference
highlighted the neflamapimod clinical development program,
including the RewinD-LB Phase 2b
study design and the supportive Phase 2a clinical data, for the
treatment of patients with dementia with Lewy bodies (DLB).
"We are pleased to have had the opportunity at this year's CTAD
conference to comprehensively present the findings in Phase 2a and
discuss the analyses that went into optimizing the Phase
2b study design for the treatment of
patients with DLB," said John Alam,
MD, Chief Executive Officer of CervoMed. "Our Phase 2b DLB study, with its optimized design, has
substantial statistical power to detect an effect on the Clinical
Dementia Rating Sum-of-boxes, and is currently actively enrolling
patients in the US, the UK, and the
Netherlands. We look forward to completing enrollment during
the first half of 2024 and then reporting initial results from the
placebo-controlled portion of the study during the second half of
2024."
Based on the learnings, the distinctions from Phase 2a in the
RewinD-LB study include, (1) the use of one dosing regimen of
neflamapimod (40mg capsules three-times-a-day, TID), based on the
dose-response analysis of the study, and on observations in AD
studies; (2) the choice of Clinical Dementia Rating Sum of Boxes
(CDR-SB) as the primary endpoint; and (3) the exclusion of patients
with Alzheimer's related co-pathology, as evaluated by plasma
levels of tau phosphorylated at position 181 (ptau181; to enrich
for such patients, the global CDR score at entry will be limited to
0.5 or 1.0). With these modifications to the design from Phase 2a,
sample size calculations (see below) indicate that the
RewinD-LB Phase 2b study has greater
than 95% statistical power (approaching 100%) to meet its primary
objective of demonstrating improvement relative to placebo on
change in CDR-SB over the course of the study.
Highlights of the presentation include the following:
- The Phase 2a inclusion criteria for the diagnosis of DLB was
able to identify and support enrollment of a robust DLB patient
population with significant attentional deficits, with >1.5
Standard Deviation (SD) deficits vs. age-adjusted norm in the
cognitive tests of attention and/or working memory at baseline.
Patients enrolled in the study had lesser decline in executive
function, with ≤1 SD deficit in cognitive tests designed to
evaluate executive function; consistent with the literature for
mild DLB.
- Clinical endpoints that can detect effects on both cognitive
and motor function (specifically, CDR-SB and the Timed Up and Go
test, TUG) performed better in the Phase 2a study with respect to
detecting improvement over placebo than endpoints that are purely
focused on evaluating cognition. The underperformance in Phase 2a
of a six cognitive test Neuropsychological Test Battery (NTB)
evaluating attention and executive function can be attributed to
ceiling effects due to (1) the modest deficits in executive
function at baseline and (2) patients in Phase 2a all receiving
cholinesterase inhibitors.
- Sample size for the potential endpoints in Phase 2b were evaluated through clinical trial
simulations that utilized individual patient data in Phase 2a for
the placebo and neflamapimod 40mg TID recipients. Based on the
simulation of 100 clinical trials with 80 patients per treatment
group, and assuming a 10% dropout rate, there is ~85% power with
the NTB, 95% power with the TUG, and >95% power with CDR-SB
(approaching 100%) to detect a treatment effect at an alpha level
of 0.05.
- Electroencephalography (EEG) evaluations in Phase 2a showed
that while there were no differences between neflamapimod and
placebo in spectral analysis, neflamapimod treatment led to a
significant dose-dependent increase vs. placebo in the beta band
seen in functional connectivity analysis. These results were
previously presented at the International Conference on Alzheimer's
and Parkinson's Diseases 2022 meeting in Barcelona, Spain (video of presentation
available here).
- In the Phase 2a study, in patients without Alzheimer's related
co-pathology (assessed by plasma ptau181) at study entry,
neflamapimod treatment led to significant improvement compared to
placebo in the change in plasma levels of glial fibrillary acidic
protein (GFAP): from baseline to week-16, GFAP was decreased by
mean 10.6 pg/mL in neflamapimod-recipients and increased by mean
14.1 pg/mL in placebo-recipients (p=0.04 for neflamapimod vs.
placebo). These data have not been previously presented and a full
presentation of the GFAP data is planned for a future scientific
conference. Plasma GFAP was recently reported as a potential
biomarker for DLB (Hamilton et al,
Psychological Medicine, 2023).
A copy of the CTAD presentation is available on the
Presentations and Publications section of CervoMed's website.
About the Phase 2b Study in
Dementia with Lewy Bodies (RewinD-LB)
The Phase 2b study, named
RewinD-LB, is a randomized, 16-week double-blind,
placebo-controlled clinical trial evaluating oral neflamapimod
(40mg three times per day) in up to 160 patients with prodromal
dementia with Lewy bodies (DLB) or mild dementia due to DLB.
Patients completing the 16-week placebo-controlled study period
will be able to continue in the study while receiving open label
neflamapimod treatment for an additional 32 weeks. Clinical sites
are located in the US, the UK, and the
Netherlands. Patients with Alzheimer's disease-related
co-pathology, assessed by a blood biomarker (plasma ptau181), will
be excluded. CervoMed expects to complete enrollment in RewinD-LB
during the first half of 2024 and then report initial results from
the placebo-controlled portion of the study during the second half
of 2024. The RewinD-LB study is funded by a $21 million grant from the National Institutes of
Health's National Institute on Aging (NIA), which will be disbursed
over the course of the study as costs are incurred. More
information, including information on active clinical trial sites,
on the RewinD-LB study is available at clinicaltrials.gov.
About CervoMed
CervoMed Inc. is a clinical-stage biotechnology company
advancing CNS-focused therapeutics to benefit patients with a range
of degenerative diseases of the brain. The Company is currently
developing neflamapimod, an investigational orally administered
small molecule brain penetrant that inhibits p38MAP kinase alpha
(p38a). Neflamapimod has the potential to treat synaptic
dysfunction, the reversible aspect of the underlying
neurodegenerative processes that cause disease in dementia with
Lewy bodies (DLB) and certain other major neurological disorders.
Neflamapimod is currently being evaluated in a Phase 2b study in patients with DLB. CervoMed was
formed in August 2023 with completion
of the merger of EIP Pharma Inc. with Diffusion Pharmaceuticals
Inc.
For more information, please visit www.cervomed.com or engage
with us on Twitter and LinkedIn.
Forward-Looking Statements
This press release includes express and implied forward-looking
statements within the meaning of the Private Securities Litigation
Reform Act of 1995, as amended, regarding the intentions, plans,
beliefs, expectations or forecasts for the future of CervoMed Inc.
(the "Company"), including, but not limited to, the therapeutic
potential of neflamapimod and anticipated timing of clinical
milestones. Terms such as "believes," "estimates," "anticipates,"
"expects," "plans," "intends," "may," "could," "might," "will,"
"should," "approximately," "potential" or other words that convey
uncertainty of future events or outcomes may identify these
forward-looking statements. Although there is believed to be
reasonable basis for each forward-looking statement contained
herein, forward-looking statements by their nature involve risks
and uncertainties, known and unknown, many of which are beyond the
Company's control and, as a result, actual results could differ
materially from those expressed or implied in any forward-looking
statement. Particular risks and uncertainties include, among other
things, those related to: the Company's available cash resources
and the availability of additional funds on acceptable terms; the
likelihood and timing of any regulatory approval of neflamapimod or
the nature of any feedback the Company may receive from the U.S.
Food and Drug Administration; the ability to implement business
plans, forecasts, and other expectations in the future; general
economic, political, business, industry, and market conditions,
inflationary pressures, and geopolitical conflicts; and the other
factors discussed under the heading "Risk Factors" in Exhibit 99.2
to the Company's Current Report on Form 8-K/A filed with the U.S.
Securities and Exchange Commission (SEC) on September 29, 2023, and other filings that the
Company may file from time to time with the SEC. Any
forward-looking statements in this press release speak only as of
the date hereof (or such earlier date as may be identified).
The Company does not undertake any obligation to update such
forward-looking statements to reflect events or circumstances after
the date of this press release, except to the extent required by
law.
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