NEW YORK, May 17, 2021 /PRNewswire/ -- Seelos
Therapeutics, Inc. (Nasdaq: SEEL), a clinical-stage
biopharmaceutical company focused on the development of therapies
for central nervous system (CNS) disorders and rare diseases, today
announced positive data from Part 1, the open-label cohort, of its
potentially registrational Proof-of-Concept study of SLS-002
(intranasal racemic ketamine) demonstrating a significant treatment
effect and a well-tolerated safety profile for Acute Suicidal
Ideation and Behavior (ASIB) in patients with Major Depressive
Disorder (MDD).
"Rapid and clinically meaningful efficacy both as an
anti-depressive and anti-suicidal therapeutic after a single
dose"
This study enrolled 17 subjects diagnosed with MDD requiring
psychiatric hospitalization due to significant risk of suicide with
a baseline score of ≥ 28 points on the Montgomery-Åsberg Depression Rating Scale
(MADRS), a score of 5 or 6 on MADRS Item-10, a score of ≥ 15 points
on the Sheehan-Suicidality Tracking Scale (S-STS) total score and a
history of previous suicide attempt(s), as confirmed on the
Columbia Suicide Severity Rating Scale (C-SSRS) with a history of
at least one actual attempt, or if the attempt was interrupted or
aborted, is judged to have been serious in intent.
"Rapid and clinically meaningful efficacy both as an
anti-depressive and anti-suicidal therapeutic after a single dose
could make SLS-002 an ideal therapy for this large unmet need of
acute suicidality in major depression," said Raj Mehra, Ph.D.,
Chairman and CEO of Seelos. "These are trying times in our
battle against the suicide epidemic, which has been exacerbated by
the COVID-19 global pandemic, and SLS-002 could create a paradigm
shift allowing better treatment for these patients."
"As a researcher, and as a psychiatrist and former clinician who
previously treated many patients with MDD and imminent risk of
suicide, I am very impressed by these data," said Tim Whitaker, MD, Chief Medical Officer of
Seelos, "We are currently training additional trial sites and look
forward to initiating Part 2 of our study, which will be
double-blind and placebo-controlled."
David V. Sheehan, M.D., offered
his perspective on the data, "There is no medication approved by
any regulatory agency for the treatment of suicidal ideation and
behavior in depression or in any mood disorder. Indeed, most
approved anti-depressants and mood stabilizers are associated with
an increased risk of treatment emergent suicidality, especially in
those under 25. Most antidepressants take three to six weeks before
delivering good, stable benefit. Medical science has not yet
achieved its long-sought goal of verifying that any medication can
provide a very rapid effect specifically on suicidal ideation and
behavior in any mood disorder. This recent early Phase 2 Seelos
open-label study data is a promising step towards achieving that
goal. If replicated in a larger placebo-controlled study, these
findings would be a historic contribution to the treatment of
suicidality."
Detailed Summary of Key Efficacy Endpoints
MADRS1:
- 76.5% response rate on Day 1 (n=17), 92.9% response rate on Day
16 (n=14) and 100% response rate on Day 29 (n=13); the latter being
14 days after the last dose on Day 15
- 35.3% remission rate on Day 1, 78.6 % remission rate on Day 16,
and 76.9% remission rate on day 29; the latter being 14 days after
the last dose on Day 15
- Total Score Baseline = 39.4, Day 1 mean = 14.5, Day 16 mean =
7.4, and Day 29 mean = 6.3
CGIS-SI/B2:
- 94% subjects had ≥ 1 point within-patient change from their
baseline on Day 1 and 100% of subjects on Day 16 had > 1 point
change and 86% had 2, 3 or 4 point within-patient change from their
baseline
- Baseline = 3.8, Day 1 mean = 1.6 and Day 16 mean = 1.1
S-STS3:
- 94% of subjects had > 14 points within-patient change from
their baseline and 1 subject (6%) = 4 points within-patient change
on Day 1
- Total Score Baseline = 22.4, Day 1 mean = 1.7, and Day 16 and
Day 29 values were 0.0 for all subjects who completed the study
protocol
PGIS-SI/B4:
- 94 % subjects had ≥ 1 point within-patient change from their
baseline on Day 1 and 100% of subjects on Day 16 had > 1 point
change and 86% had 2 or 3 point within-patient change from their
baseline
- Baseline = 3.5, Day 1 mean = 1.6, and Day 16 mean = 1.0
MADRS Suicide Item-105:
- 94% response rate on Day 1 and 100% response rate on Day
16
- Baseline = 5.2, Day 1 mean = 0.8; Day 16 mean = 0.1; Day 29
mean = 0.0
SLS-002 SHOWED
CLINICAL IMPROVEMENTS ACROSS ALL FOUR SCALES
|
|
|
|
|
|
BASELINE
(n=17)
|
DAY 1
(n=17)
|
DAY 16
(n=14)
|
MADRS
(0-60 scale, ≤12 is
remission)
|
39.4
|
14.5
|
7.4
|
CGIS-SI/B
(1-5 scale, 1=not at
all, 5=extremely suicidal)
|
3.8
|
1.6
|
1.1
|
S-STS
(0-52 scale, higher
score equated to higher suicidality)
|
22.4
|
1.7
|
0.0
|
PGIS-SI/B
(1-5 scale, 1=not
present, 5=extremely severe)
|
3.5
|
1.6
|
1.0
|
MADRS Item
10
(0-6 scale, ≤3 is
defined as a response)
|
5.2
|
0.8
|
0.1
|
|
Source: Seelos
Therapeutics Corporate Presentation
|
Detailed Summary of Safety Results
SLS-002 was well tolerated, with 47% of subjects having at least
one treatment emergent adverse event. There were no serious adverse
events, and all adverse events were mild or moderate, mostly
transient in nature, and with no new or unique safety signals
identified. No adverse events related to blood pressure or other
vital sign changes were reported in this study population. The most
common treatment emergent adverse events (three subjects each) were
headache, dizziness, and feeling abnormal.
Clinician Administered Dissociative States Scale
(CADSS)6
- Change from baseline (at 40 minutes – correlating roughly with
maximum plasma concentrations) = 3.8 after first dose and 1.0 at 1
hour post first dose
- Change from pre-dose baseline 2.6 on Day 4 (at 40 minutes)
after second dose and 0.3 on Day 8 (at 40 minutes) after third
dose
Hemodynamic Effects
- Systolic Blood Pressure (mm Hg) : Baseline = 119.8; 1 hour
(post first dose) = 126.3; 2 hours (post first dose) = 121.1
- Diastolic Blood Pressure (mm Hg) : Baseline = 78.9; 1 hour
(post first dose) = 81.1; 2 hours (post first dose) = 78.5
Modified Observer's Assessment of Alertness/Sedation Scale
(MOAA/S)7
- Baseline (pre-dose) 17.6% scored a 4 (i.e., 82.4% scored a 5)
and post dose at the 15-minute timepoint on Day 1. Beginning 30
minutes post dose and all timepoints thereafter, > 82.4% scored
a 5.
- No subject scored < 4 at any timepoint.
Four subjects discontinued the trial prior to completion. Two
withdrew consent, one had an adverse event unrelated to study drug,
and one was lost to follow up. All four were "responders" on the
MADRS, and two were in "remission" on the MADRS scale on Day 1. All
four received less than five doses and had a clinically significant
reduction in measures of suicidality – scoring a zero on the
S-STS total score, and three of the four subjects had a decrease on
both the CGIS-SI/B, and the PGIS-SI/B from a 4 (severe) to a 1
(none), and the other subject reduced from a CGIS-SI/B of a 4, and
a PGIS-SI/B of 5 (extremely severe) to a 2 (mild).
1 MADRS scale range 0-60, higher scores
indicating more severe depression. Response is defined as a 50%
reduction from baseline and remission is defined as a total score
< 12.
2 Clinical Global Impression of Severity for
Suicidal Ideation and Behavior (CGIS-SI/B) is a 5-item
clinician-rated measure of suicidality-specific symptom severity,
originally deployed in the International Suicide Prevention Trial,
and is defined as 1 (not at all suicidal) to 5 (among the most
extremely suicidal)
3 S-STS is a clinician-rated outcome measure which
assesses SI/B on a standard 22-item scale, as well as multiple
patient and clinician-rated items. The first 16 items are rated on
a Likert-type scale ranging from 0 (not at all) to 4 (extremely),
where select scoring (i.e., 4 specific items are scored based on
the highest score on 2 of those items) yields a total score ranging
from 0 to 52.
4 Patient Global Impression of Severity for
Suicidal Ideation and Behavior (PGIS-SI/B is a 5-point,
patient-rated scale for assessing the subject's view of the general
severity of their illness, which is rated on a single-item
Likert-type scale ranging from 1 (not present) to 5 (extremely
severe).
5 MADRS Item-10,0-6 scale. measures presence of
suicidal thoughts or plans with a response defined as a score of
< 3.
6 CADSS is a standardized instrument used to measure
present-state dissociative symptoms. The scale includes
23 subjective items to be answered by the subject according to
a 5-point scale (0 = not at all, 1 = mild, 2 = moderate,
3 = severe, and 4 = extreme). Scores are totaled overall and as
3 components: depersonalization, derealization, and amnesia.
For each of these components and the total score, a higher score
reflects a more severe condition. CADSS total score range is
0-92.
7 0-5 scale with a score of 5 defined as awake or
responsive, and a score of 0 defined as general anesthesia or
unresponsive.
Conference Call Information
Seelos will host a conference call today, Monday, May 17th, at 8:30am ET, to discuss the results. On the call
from Seelos will be Raj Mehra, Ph.D., Chairman and CEO and
Tim Whitaker, M.D., Chief Medical
Officer.
Additionally, David V. Sheehan,
M.D., the Distinguished University Health Professor Emeritus at the
University of South Florida College of
Medicine, will be on the call as well to discuss this
groundbreaking data.
Dial-in and Webcast Information for Monday May 17th at 8:30am ET
Domestic: (877) 407-0789
International: (201) 689-8562
Conference ID: 13719894
Webcast: http://public.viavid.com/index.php?id=144999
The study is a multicenter, two-part clinical
trial, comprised of an open-label cohort followed by a randomized,
double-blind, placebo-controlled study. The purpose of the study is
to evaluate the efficacy, safety, and tolerability of repeat doses
of SLS-002 (intranasal racemic ketamine) in addition to standard of
care on the symptoms of MDD and suicidality in patients who are
assessed to be at imminent risk of suicide.
After admission to the emergency room or hospital, each subject
participates in a one- to two–day screening phase, a 16-day
treatment phase including Standard of Care (SOC) during which study
drug will be administered two times per week (total of five doses)
, and a two-week safety follow-up phase for a total of up to five
weeks of study participation. Subjects will be treated as
inpatients for approximately seven days (including screening), and
assuming the subject meets readiness for discharge criteria, will
be discharged on Day 6 to continue the trial as outpatients,
provided it is clinically appropriate to do so. Subjects will
return to the clinic to receive study drug and to undergo study
assessments two times per week until Day 16. Subjects will be
evaluated for efficacy using multiple psychometric scales and for
safety using clinical laboratory assessments, electrocardiograms
(ECGs), vital signs, and physical examinations. After the last dose
of study drug, subjects will continue to be monitored for safety
for two weeks, including four in-person safety follow-up visits up
to day 29/30.
If you or a loved one are having thoughts of suicide, please
seek immediate medical help, go to your nearest emergency room, or
call the National Suicide Prevention Lifeline at
1-800-273-8255.
About SLS-002
SLS-002 is intranasal racemic ketamine with investigational new
drug applications for the treatment of ASIB in MDD or
Post-Traumatic Stress Disorder (PTSD). SLS-002 was originally
derived from a Javelin Pharmaceuticals, Inc./Hospira, Inc. program
with 16 clinical studies involving approximately 500 subjects.
SLS-002 is being developed to address an unmet need for a therapy
to treat suicidality in the U.S. Traditionally, anti-depressants
have been used in this setting, but many of the existing treatments
are known to contribute to an increased risk of suicidal thoughts
in some circumstances, and if they are effective, it often takes
weeks for the full therapeutic effect to be manifested. Based on
information gathered from the databases of the Agency for
Healthcare Research and Quality, there were more than 1,000,000
visits to emergency rooms for suicide attempts in 2013in the U.S.
alone. Experimental studies suggest ketamine has the potential to
be a rapid, effective treatment for depression and suicidality.
About David V. Sheehan, MD,
MBA
David V. Sheehan, M.D., M.B.A. is
Distinguished University Health Professor Emeritus at the
University of South Florida College of
Medicine. He was Professor of Psychiatry, Director of Psychiatric
Research and Director of the Depression and Anxiety Disorders
Research Institute at the University of South
Florida College of Medicine and Professor of Psychology at
the University of South Florida College
of Arts and Sciences. He completed his residency training in
psychiatry at Massachusetts General Hospital and Harvard Medical School. At Harvard Medical School, where he was Assistant
Professor of Psychiatry, he was on the full-time faculty for 12 1/2
years. He was the Director of Anxiety Research and Director of the
Psychosomatic Medicine Clinic at Massachusetts General Hospital. He
received his MBA (summa cum laude) from the University of South Florida. He served as Director
of Psychiatric Research for the Department of Psychiatry and
Behavioral Medicine at the University of South
Florida College of Medicine from 1985-2007. He has written
over 550 abstracts and 300 publications, including a bestseller The
Anxiety Disease (which sold over half a million copies). He
has been awarded over $20 million for
130 research grants. He was awarded two patents by the United
States Patent and Trademark Office in 1996 and 2015. He has given
expert testimony to the Unites States Congress. He was
elected as a member of the American College of Psychiatrists, is a
Distinguished Life Fellow of the American Psychiatric Association
and is a Charter Member of the National Academy of Inventors. Among
other honors, he has been included in "The Best Doctors in America"
published by Woodward/White Inc. every year from 1992 until his
retirement in 2010.
About Seelos Therapeutics
Seelos Therapeutics, Inc. is a clinical-stage biopharmaceutical
company focused on the development and advancement of novel
therapeutics to address unmet medical needs for the benefit of
patients with CNS disorders and other rare diseases. The Company's
robust portfolio includes several late-stage clinical assets
targeting indications including ASIB in MDD or
PTSD, amyotrophic lateral sclerosis, Sanfilippo syndrome,
Parkinson's Disease, other psychiatric and movement disorders and
orphan diseases.
For more information, please visit our
website: http://seelostherapeutics.com, the content of which
is not incorporated herein by reference.
Forward Looking Statements
Statements made in this press release, which are not
historical in nature, constitute forward-looking statements for
purposes of the safe harbor provided by the Private Securities
Litigation Reform Act of 1995. These statements include, among
others, those regarding the significance of the data from
Part 1 (SLS-002-101), the open-label cohort, of Seelos'
registrational Proof-of-Concept study of SLS-002 (intranasal
racemic ketamine) (the "Study") and Seelos' additional Study plans.
These statements are based on Seelos' current expectations and
beliefs and are subject to a number of risks and uncertainties that
could cause actual results to differ materially from those
described in the forward-looking statements. Risks associated with
Seelos' business and the topline clinical results described herein
include, but are not limited to, the risk of not successfully
executing its preclinical and clinical studies, or continuing the
Study, and not gaining marketing approvals for its product
candidates, the risk that prior clinical results may not be
replicated in future studies and trials (including the risk that
the clinical results from the planned Part 2 of the Study are not
replicated or are materially different from the topline clinical
results of Part I of the Study), the risks that clinical study
results may not meet any or all endpoints of a clinical study and
that any data generated from such studies may not support a
regulatory submission or approval, the risks associated with the
implementation of a new business strategy, the risks related to
raising capital to fund its development plans and ongoing
operations, risks related to Seelos' current stock price, risks
related to the global impact of COVID-19, as well as other factors
expressed in Seelos' periodic filings with the U.S. Securities and
Exchange Commission, including its most recent Annual Report on
Form 10-K and Quarterly Reports on Form 10-Q. Although we believe
that the expectations reflected in our forward-looking statements
are reasonable, we do not know whether our expectations will prove
correct. You are cautioned not to place undue reliance on these
forward-looking statements, which speak only as of the date hereof,
even if subsequently made available by us on our website or
otherwise. We do not undertake any obligation to update, amend or
clarify these forward-looking statements, whether as a result of
new information, future events or otherwise, except as may be
required under applicable securities laws.
Contact Information:
Anthony Marciano
Head of Corporate Communications
Seelos Therapeutics, Inc. (Nasdaq: SEEL)
300 Park Avenue
New York, NY 10022
(646) 293-2136
anthony.marciano@seelostx.com
www.seelostherapeutics.com
https://twitter.com/seelostx
https://www.linkedin.com/company/seelos
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