-- Study meets one of the two
analyses of primary efficacy endpoint: statistically significant
dose-response in six-minute walk test (6MWT) at Day 180
-- Longeveron to hold conference
call today at 8:00 AM EDT
Miami, FL – August 13th, 2021 -- InvestorsHub NewsWire
-- Longeveron Inc. (NASDAQ: LGVN) ("Longeveron" or "Company"), a clinical
stage biotechnology company developing cellular therapies for
chronic aging-related and life-threatening conditions, today
announced results from the Company's Phase 2b trial titled: A Phase
2b, Randomized, Blinded and Placebo-Controlled Trial to Evaluate
the Safety and Efficacy of Lomcecel-B Infusion in Patients With
Aging Frailty (the "Phase 2b trial"). Lomecel-B is a proprietary
allogeneic product comprised of medicinal signaling cells (MSCs)
from the bone marrow of adult donors and culture-expanded in
Longeveron's current good manufacturing practice (cGMP) cell
processing facility. The Phase 2b trial, which was partially funded
by a Small Business Innovation Research (SBIR) grant from the
National Institute on Aging (NIA), evaluated the safety and
efficacy of a single peripheral intravenous infusion of four
different doses of Lomecel-B cell therapy (25 million (n=37), 50
million (n=31), 100 million (n=34) and 200 million (n=16) cells;
sample size reflects any subject that was randomized and received
an infusion) compared to placebo (n=30), on signs and symptoms of
Aging Frailty, including mobility and exercise tolerance.
The pre-specified statistical analysis plan for the primary
efficacy endpoint, change in six-minute walk test distance at 180
days post-infusion, involved a primary analysis and a secondary
analysis:
-
Primary analysis of the primary efficacy endpoint: The primary
analysis compared the change from baseline in 6MWT distance for the
four Lomecel-B cohorts to the placebo cohort at Day 180. There were
statistically significant increases in the highest 3 doses--50
million, 100 million and 200 million Lomecel-B cohorts--and no
significant changes in the placebo or lowest dose of Lomecel-B (25
million=7.8 meters, p=0.5040; 50 million=35.8 meters, p=0.0053; 100
million=24.9 meters p=0.0443; 200 million=49.3 meters, p=0.0065;
placebo=8.0 meters, p=0.5371). However, after adjusting for
multiple comparisons using the Hochberg method (1988), the four
Lomecel-B cohorts did not show a statistically significant
placebo-adjusted difference (Δ)
(25 million
Δ=-0.2, p=0.9902; 50 million
Δ=27.7, p=0.1279; 100 million
Δ=16.8, p=0.3472; 200 million
Δ=41.3, p=0.0635).
-
Secondary analysis of the primary efficacy endpoint: The
secondary analysis was to determine whether a dose-response
relationship exists using the multiple comparisons and modeling
approach by Bretz et. al (2003). The results showed a clear,
statistically significant dose-response curve at day 180. Among the
various dose-response curves evaluated (Emax, Linear, Exponential,
Quadratic, and Sigmoid Emax), all had p-values of less than 0.05,
with the Sigmoid Emax model having the most significant
dose-response relationship (p=0.0170).
Despite not achieving the statistical significance for the
pairwise comparison to placebo at Day 180, significant differences
from placebo were observed at Day 270, which was a pre-specified
exploratory endpoint (25 million
Δ=27.5, p=0.1530; 50 million
Δ=49.2, p=0.0122; 100 million
Δ=31.0, p=0.1071; 200 million
Δ=63.4, p=0.0077).
"Improving physical function in older adults with frailty is one
of the primary goals in geriatric medicine," said Dr. Jorge G.
Ruiz, MD, geriatrician at the Miami Veterans Affairs Healthcare
System, Geriatric Research, Education and Clinical Center (GRECC),
the study site enrolling the largest number of subjects. "The fact
that patients enrolled in this study, with an average age of 75 and
with clear mobility limitations, showed 6-month and 9-month
placebo-adjusted increases in walking distance of 40 meters and 63
meters, respectively (200 million cell dose), is significant for a
number of reasons. Frailty is associated with poor clinical
outcomes and high healthcare utilization and being able to improve
and extend walking distance suggests preservation of function and
potentially independence," Dr. Ruiz continued. "I would consider
these results clinically significant and relevant for the older
veteran population since one third of American Veterans older than
65 years have frailty."
"We are very pleased to report a statistically significant dose
response curve with our experimental cell therapy," commented Geoff
Green, CEO of Longeveron Inc. "One of the main objectives of this
trial was to determine whether a dose response relationship could
be demonstrated in the primary efficacy endpoint, so this finding
is important for the research program," Mr. Green continued.
"Furthermore, the safety profile of Lomecel-B continues to look
very good, with no Lomecel-B related Serious Adverse Events
reported in this study, which is consistent with previous clinical
trial data."
The study's key secondary endpoints were day 180 change in the
patient reported outcome questionnaire PROMIS—Physical
Function—Short Form 20a (SF-20a) total score and day 180 change in
serum levels of tumor necrosis factor alpha (TNF-a), an
inflammatory cytokine. Lomecel-B cohorts did not show a
statistically significant difference compared to the placebo cohort
in the SF-20a score, and the TNF-a analysis is pending. The
remainder of the efficacy endpoints, which included assessments of
physical function, sexual function, fear and risk of falling,
depression, cognition, frailty status, pulmonary function, and
clinical outcomes, were considered exploratory and
Lomecel-B-treated groups did not show significant differences
versus placebo at most of the time points for any of the
endpoints.
The main inclusion criteria for entry into the trial were
subjects 70-85 years of age, a screening 6MWT of between 200 to 400
meters, a Canadian Health and Safety Assessment (CHSA) Clinical
Frailty Scale score of 5 (mildly frail) to 6 (moderately frail),
and a minimum serum TNF-a of = 2.5 pg/mL.
Longeveron plans to review the trial data during an upcoming
steering committee comprised of independent frailty experts, and
plan out next steps for the program. The Company plans to present
clinical data from this trial at the 2021 International Conference
on Frailty & Sarcopenia Research (ICFSR) on September 29th at
11:30 AM EDT during a round table presentation.
Mr. Green said, "We look forward to engaging with our experts
and potentially regulatory authorities to review the data and to
advance into the next trial. I want to thank the subjects, their
families, and physicians for their participation in this important
study, and the NIH's National Institute on Aging for its generous
support." Mr. Green added, "We are also expecting our Phase 1/2
"HERA" trial data this quarter, which is designed to evaluate
Lomecel-B infusion's effect on immune response to influenza
vaccination in Aging Frailty subjects, and we anticipate initiating
the Phase 2 Japanese Aging Frailty this year."
Conference Call and Webcast
Management will host a conference call today at 8:00 a.m.
Eastern Time to discuss the Company's second quarter 2021 financial
results and provide a business update.
The conference call will be available via telephone by dialing
toll free 1-844-200-6205 for U.S. callers; 1-646- 904-5544 for
local callers; or + 44 208-068-2558 for international callers and
using entry code 874656. An audio replay of the call will be
available through August 19, 2021.
A webcast of the call may be accessed from the "Events &
Presentations" page on the Longeveron website at https://investors.longeveron.com/events-and-presentations/default.aspxby
selecting today's date from the "Upcoming Events" calendar followed
by the "Webcast" link that appears beneath. The recorded webcast
will remain accessible for one year through August 13, 2022.
About the US Phase 2b Aging Frailty Trial:
The primary objective of this multi-center study is to assess
the effect of Lomecel-B on exercise tolerance and endurance via the
six-minute walk test (6MWT). Additional endpoints include gait
speed, grip strength, short physical performance battery (SPPB),
Performance Oriented Mobility Assessment (POMA; measures subject's
risk of falling), the Falls Efficacy Scale (measures subject's fear
of falling), depression, sexual function, cognition, various
patient reported outcomes (PROs) and activities of daily living
(ADLs), and blood-based biomarkers. One hundred and forty-eight
(148) subjects were randomized and received a single peripheral
intravenous infusion of Lomecel-B (25 million cells, 50 million
cells, 100 million cells or 200 million cells), or placebo,
followed by a 52-week observation period to evaluate safety and
efficacy. The Phase 2b trial was conducted at eight hospitals and
clinics, primarily in South Florida, including the Miami VA
Healthcare System, and was funded by a Small Business Innovation
Research (SBIR) grant from the NIH's National Institute on Aging
(NIA).
About Aging Frailty
Aging Frailty is a life-threatening geriatric condition
affecting approximately 15% of Americans over the age of 65, or 8.1
million individuals. Aging Frailty patients are vulnerable to poor
clinical outcomes compared to their age-matched peers despite
sharing similar comorbidities and demographics, and therefore it is
considered an extreme form of unsuccessful aging. Clinically,
frailty manifests as a combination of symptoms that includes loss
of muscle and decreased strength, slowed walking, low activity and
energy levels, poor
endurance, nutritional deficiencies, weight loss and fatigue.
Aging Frailty is also associated with chronic low- level sterile
inflammation. Individuals with Aging Frailty have decreased
reserves and a reduced ability to cope with minor illnesses or
stressors that would normally have minimal impact, such as an
infection or a fall. As a result, the individual may be more likely
to be hospitalized, need long term care, or die. Inflammation can
contribute to the physical decline in Aging Frailty through
multiple mechanisms, including detrimental effects on muscles, bone
tissue, the immune system, cardiovascular function, and
cognition.
The necessity for identifying patients with Aging Frailty is
well-acknowledged in the geriatric community, and the treatment of
Aging Frailty and promotion of healthful aging are recognized
priorities of the National Academy of Medicine and NIA/NIH. Despite
the pressing need for interventions, there are no FDA-approved
therapies that can slow down, reverse, or prevent Aging
Frailty.
About Longeveron Inc.
Longeveron is a clinical stage biotechnology company developing
cellular therapies for specific aging-related and life-threatening
conditions. The Company's lead investigational product is the
LOMECEL-BTM cell-based therapy product ("Lomecel-B"), which is
derived from culture-expanded medicinal signaling cells (MSCs) that
are sourced from bone marrow of young, healthy adult donors.
Longeveron believes that by using the same cells that promote
tissue repair, organ maintenance, and immune system function, it
can develop safe and effective therapies for some of the most
difficult disorders associated with the aging process and other
medical disorders. Longeveron is currently sponsoring Phase 1 and 2
clinical trials in the following indications: Aging Frailty,
Alzheimer's disease, the Metabolic Syndrome, Acute Respiratory
Distress Syndrome (ARDS), and hypoplastic left heart syndrome
(HLHS). The Company's mission is to advance Lomecel-B and other
cell-based product candidates into pivotal Phase 3 trials, with the
goal of achieving regulatory approvals, subsequent
commercialization, and broad use by the healthcare community.
Additional information about the Company is available at https://www.longeveron.com/.
Forward-Looking and Other Statements
Certain statements in this press release that are not historical
facts are forward-looking statements that reflect management's
current expectations, assumptions, and estimates of future
performance and economic conditions, and involve risks and
uncertainties that could cause actual results to differ materially
from those anticipated by the statements made herein.
Forward-looking statements are generally identifiable by the use of
forward-looking terminology such as "believe," "expects," "may,"
"looks to," "will," "should," "plan," "intend," "on condition,"
"target," "see," "potential," "estimates," "preliminary," or
"anticipates" or the negative thereof or comparable terminology, or
by discussion of strategy or goals or other future events,
circumstances, or effects. Moreover, forward-looking statements in
this release include, but are not limited to, statements about the
ability of our clinical trials to demonstrate safety and efficacy
of our product candidates, and other positive results; the timing
and focus of our ongoing and future preclinical studies and
clinical trials; the size of the market opportunity for our product
candidates, the beneficial characteristics, safety, efficacy and
therapeutic effects of our product candidates; our ability to
obtain and maintain regulatory approval of our product candidates,
our plans and ability to obtain or protect intellectual
property
rights, including extensions of existing patent terms where
available and our ability to avoid infringing the intellectual
property rights of others. Further information relating to factors
that may impact the Company's results and forward-looking
statements are disclosed in the Company's filings with the SEC. The
forward- looking statements contained in this press release are
made as of the date of this press release, and the Company
disclaims any intention or obligation, other than imposed by law,
to update or revise any forward- looking statements, whether as a
result of new information, future events, or otherwise.
Investor Contact:
Brendan Payne
Stern Investor Relations 212-698-8695 brendan.payne@sternir.com
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