BioXcel Therapeutics, Inc. (“BioXcel” or the “Company”) (Nasdaq:
BTAI), a clinical-stage biopharmaceutical company utilizing
artificial intelligence to identify improved therapies in
neuroscience and immuno-oncology, today announced that BXCL501, the
Company’s proprietary, orally dissolving thin film formulation of
dexmedetomidine, met the primary and secondary endpoints of the
TRANQUILITY trial at the 60 mcg dose level. Topline results from
the evaluated doses showed that BXCL501 was generally well
tolerated, with rapid and durable reductions observed in measures
of acute agitation with the 60 mcg dose.
The TRANQUILITY Phase 1b/2 randomized, placebo
controlled, adaptive, ascending dose finding study enrolled 54
patients in assisted living facilities with agitation related to
dementia, 87 percent of which had Alzheimer’s disease. Patients
received BXCL501 at either 30 mcg (n=16), 60 mcg (n=20), 90 mcg
(n=4) or placebo (n=14). The study’s primary safety and
tolerability endpoints were met, with no severe or serious adverse
events reported. Adverse events in the trial included hypotension
(10%, 0% and 0%, for 60 mcg, 30 mcg and placebo, respectively),
orthostatic hypotension (5%, 6.3% and 0%, respectively) and
dizziness (5%, 6.3% and 0%, respectively). The most common adverse
event was somnolence characterized as either mild (55% for 60 mcg,
50% for 30 mcg and 7.1% for placebo) or moderate (5%, 0% and 0%,
respectively). Orthostasis and dizziness were observed in some
patients receiving the highest 90 mcg dose. Higher exposure levels
of BXCL501 were observed in this elderly patient population
compared to earlier trials and, as a result, the Company focused on
studying the 30 and 60 mcg doses. Notably, there were no reported
cases of syncope or falls in any of the patients studied.
The trial met its secondary efficacy endpoints
with the 60 mcg dose compared to placebo in all three primary
agitation scales—the Positive and Negative Syndrome
Scale-Excitatory Component (“PEC”), the Pittsburgh Agitation Scale
(“PAS”), and the Modified Cohen-Mansfield Agitation Inventory
(“Mod-CMAI”)—demonstrating statistically significant and clinically
meaningful reductions in total scores at two hours post-dosing. The
reductions were both rapid and durable with numerical separation
from placebo in PEC total score seen as early as 30 minutes, and
with statistically significant separation from placebo in both PEC
and PAS total scores observed at 60 minutes* and lasting through
eight hours post-dosing. The 30 mcg dose cohort showed numerical
improvements at all three measures.
Outcomes from the PEC, PAS, and Mod-CMAI for the
60 mcg, 30 mcg and placebo cohorts are below.
Summary of Topline Efficacy Results at
120 Minutes
|
60 mcg(n=20) |
30 mcg(n=16) |
Placebo(n=14) |
Reduction in PEC Total Scorevs.
Baseline |
-7.1(P=0.0011) |
-5.4(P=0.0813) |
-2.9 |
|
|
|
|
|
|
Response Rate(% of Patients Achieving
>40%Reduction in PEC Scores) |
70 |
% |
25 |
% |
7% |
|
Reduction in PAS Total Score vs. Baseline |
-5.9(P<0.0001) |
-3.9(P=0.0961) |
-2.5 |
|
Reduction in Mod-CMAI Total Score vs.
Baseline* |
-14.0(P<0.0001) |
-8.0(P=0.0591) |
-3.2 |
|
* Mod-CMAI was not measured at 60 minutes
Efficacy was further evaluated using two
additional measures of agitation-— the Agitation and Calmness
Evaluation Scale (“ACES”; P=0.0006) and Clinical Global Impression
– Improvement Scale (“CGI-I”; P<0.0001; 90% responder rate)—each
of which showed statistically significant improvements in ratings
with the 60 mcg dose level compared to placebo at two hours
post-dosing. The 30 mcg dose cohort showed numerically greater
rates of clinical response versus placebo.
“We are very encouraged by the promising topline
results from the TRANQUILITY study, which was designed to identify
a recommended dose of BXCL501 for a potential pivotal study in
dementia patients suffering from agitation. Following decades of
research, there are still no effective treatments that directly
target agitation commonly seen with dementia patients, and we are
thrilled by the potential of being the first to develop a therapy
designed to address this significant patient and caregiver need,”
said Vimal Mehta, Chief Executive Officer of BioXcel. “Based on the
results observed, we believe BXCL501 has broad potential in
treating the full spectrum of agitation in patients with dementia.
We look forward to advancing BXCL501 into a late-stage study this
year following dialogue with the FDA.”
About TRANQUILITY
The randomized, double-blind,
placebo-controlled, ascending dose, adaptive Phase 1b/2 study was
designed to evaluate the efficacy, pharmacokinetics, safety, and
tolerability of BXCL501 in adults 65 years and older who exhibit
acute agitation associated with all forms of dementia, including
Alzheimer's disease. Following the completion of each dose cohort,
a safety and tolerability review was performed to determine the
next tested dose. The study is designed to assess agitation as
measured by the changes from baseline in PAS and PEC total scores,
as well as by improvements from baseline in the Mod-CMAI total
score.
Conference Call
BioXcel will host a conference call and webcast
today at 8:30 a.m. ET. To access the call, please dial 877-407-2985
(domestic) and 201-378-4915 (international). A live webcast of the
call will be available on the Investors sections of the BioXcel
website at www.bioxceltherapeutics.com. The replay will be
available through January 19, 2020.
About Agitation Associated with
Dementia
Dementia is a neurocognitive condition caused by
damage to brain cells that leads to a decline in cognitive
abilities and independent function. It affects approximately 6
million individuals in the United States, with Alzheimer’s disease
accounting for up to 80% of these cases. During the course of the
disease, patients with dementia often suffer from psychological and
behavioral symptoms, such as agitation, which has been reported in
up to 70% of patients. Agitation associated with dementia can
negatively affect both the patient and caregiver’s quality of life.
Caregiver burden can contribute significantly to burnout, which can
result in premature institutionalization of the patient. Treating
agitation associated with dementia has been a challenge for
providers as there are currently no FDA-approved
therapies for the treatment of dementia-related agitation, and
off-label therapies have black box warnings associated with their
use.
About the Positive and Negative Syndrome
Scale-Excitatory Component Score (PEC or PANSS-EC)
The PEC total score is a validated endpoint for
measuring acute agitation in schizophrenia and bipolar patients.
This scale is used in clinical research to quantify the severity of
a patient’s acute agitation. The PEC rating evaluates 5 elements
associated with agitation: poor impulse control, tension,
hostility, uncooperativeness, and excitement; each scored 1
(minimum) to 7 (maximum). The PEC total score is the sum of these 5
elements and thus ranges from 5 to 35.
About the Pittsburgh Agitation Scale
(PAS)
PAS is a validated instrument used to monitor the severity of
agitation associated with dementia. The PAS measures 4 behavior
groups: aberrant vocalization, motor agitation, aggressiveness, and
resisting to care. The groups are evaluated on a scale from 0 to 4,
with 0 defined as no agitation present and 4 defined as the highest
form of agitation. The PAS total score ranges from 0 to 16.
Modified Cohen-Mansfield Agitation
Inventory (Mod-CMAI)
Mod-CMAI is an inventory consisting of 29
behaviors, each rated on a 7-point scale of frequency with 1
defined as never occurring and 7 defined as several times an hour.
Only behaviors manifested by the subject at baseline were assessed
throughout the study.
About BXCL501
BXCL501 is an investigational, proprietary,
orally dissolving thin film formulation of dexmedetomidine, a
selective alpha-2a receptor agonist for the treatment of agitation
and opioid withdrawal symptoms. BioXcel believes that BXCL501
directly targets a causal agitation mechanism, and the Company has
observed anti-agitation results in multiple clinical studies across
several neuropsychiatric disorders. BXCL501 has been granted Fast
Track Designation by the U.S. Food and Drug Administration for the
acute treatment of agitation in patients with schizophrenia,
bipolar disorders, and dementia. BXCL501 has been studied in two
Phase 3 trials (SERENITY I and II) for the acute treatment of
agitation associated with schizophrenia and bipolar disorders. This
product candidate was also evaluated in a Phase 1b/2 trial
(TRANQUILITY) for the acute treatment of agitation associated with
dementia and is currently being evaluated in a Phase 1b/2 study
(RELEASE) for the treatment of opioid withdrawal symptoms. The
Company also plans to initiate a Phase 2 trial in hospitalized
patients suffering from agitation associated with delirium within
the next several months.
BioXcel Therapeutics, Inc.
BioXcel Therapeutics, Inc. is a clinical-stage
biopharmaceutical company focused on drug development that utilizes
artificial intelligence to identify improved therapies in
neuroscience and immuno-oncology. BioXcel's drug re-innovation
approach leverages existing approved drugs and/or clinically
evaluated product candidates together with big data and proprietary
machine learning algorithms to identify new therapeutic indices.
BioXcel's two most advanced clinical development programs are
BXCL501, an investigational sublingual thin film formulation in
development for acute treatment of agitation resulting from
neuropsychiatric disorders, and BXCL701, an investigational orally
administered systemic innate immunity activator in development for
treatment of a rare form of prostate cancer and for treatment of
pancreatic cancer in combination with other immuno-oncology agents.
For more information, please visit www.bioxceltherapeutics.com.
Forward-Looking Statements
This press release includes “forward-looking
statements” within the meaning of the Private Securities Litigation
Reform Act of 1995. Forward-looking statements in this press
release include but are not limited to the timing and data from
clinical development initiatives and trials for BXCL501, dialogue
with the FDA and the future development of BXCL501, and the
Company’s corporate strategy. When used herein, words including
“anticipate,” “being,” “will,” “plan,” “may,” “continue,” and
similar expressions are intended to identify forward-looking
statements. In addition, any statements or information that refer
to expectations, beliefs, plans, projections, objectives,
performance, or other characterizations of future events or
circumstances, including any underlying assumptions, are
forward-looking. All forward-looking statements are based upon
BioXcel's current expectations and various assumptions. BioXcel
believes there is a reasonable basis for its expectations and
beliefs, but they are inherently uncertain.
BioXcel may not realize its expectations, and
its beliefs may not prove correct. Actual results could differ
materially from those described or implied by such forward-looking
statements as a result of various important factors, including,
without limitation, its limited operating history; its incurrence
of significant losses; its need for substantial additional funding
and ability to raise capital when needed; its limited experience in
drug discovery and drug development; its dependence on the success
and commercialization of BXCL501 and BXCL701 and other product
candidates; the failure of preliminary data from its clinical
studies to predict final study results; failure of its early
clinical studies or preclinical studies to predict future clinical
studies; its ability to receive regulatory approval for its product
candidates; its ability to enroll patients in its clinical trials;
undesirable side effects caused by BioXcel’s product candidates;
its approach to the discovery and development of product candidates
based on EvolverAI is novel and unproven; its exposure to patent
infringement lawsuits; its ability to comply with the extensive
regulations applicable to it; impacts from the COVID-19 pandemic;
its ability to commercialize its product candidates; and the other
important factors discussed under the caption “Risk Factors” in its
Quarterly Report on Form 10-Q for the quarterly period ended
September 30, 2020, as such factors may be updated from time to
time in its other filings with the SEC, which are accessible on the
SEC’s website at www.sec.gov and the Investors section of our
website at www.bioxceltherapeutics.com.
These and other important factors could cause
actual results to differ materially from those indicated by the
forward-looking statements made in this press release. Any such
forward-looking statements represent management’s estimates as of
the date of this press release. While BioXcel may elect to update
such forward-looking statements at some point in the future, except
as required by law, it disclaims any obligation to do so, even if
subsequent events cause our views to change. These forward-looking
statements should not be relied upon as representing BioXcel’s
views as of any date subsequent to the date of this press
release.
Contact Information:
BioXcel Therapeutics,
Inc.www.bioxceltherapeutics.com
Investor Relations:John
Grazianojgraziano@troutgroup.com1.646.378.2942
Media:Julia
Deutschjdeutsch@troutgroup.com1.646.378.2967
Source: BioXcel Therapeutics
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