Intra-Cellular Therapies, Inc. (Nasdaq:ITCI), a
biopharmaceutical company focused on the development and
commercialization of therapeutics for central nervous system (CNS)
disorders, today announced positive topline results from Study 403
evaluating lumateperone 42mg as monotherapy in the treatment of
major depressive episodes in patients with major depressive
disorder with mixed features and in patients with bipolar
depression with mixed features.
Lumateperone 42mg given once daily met the primary endpoint in
the study by demonstrating a statistically significant and
clinically meaningful reduction in the MADRS total score compared
to placebo at Week 6, as follows:
Primary Endpoint: Change from baseline vs. placebo on the
MADRS Total Score at Week 6 (ITT study population)
Least Squares (LS) Mean Reduction vs.
LS Mean Difference1
Cohen’s d effect size
Combined patient population of MDD with mixed features and bipolar
depression with mixed features
Population of patients with MDD with mixed features
Population of patients with bipolar depression with mixed
1 Rounded to nearest tenth.
Lumateperone 42mg also met the key secondary endpoint in the
study by demonstrating a statistically significant and clinically
meaningful reduction in the CGI-S score compared to placebo at Week
6 in the combined patient population of MDD with mixed features and
bipolar depression with mixed features (p<0.0001; ES= 0.59),
patients with MDD with mixed features (p=0.0003; ES= 0.57), and
patients with bipolar depression with mixed features (p<0.0001;
In this study, lumateperone was generally safe and well
tolerated, with a side effect profile consistent with prior
lumateperone trials. The most commonly reported adverse events that
were observed at a rate greater than or equal to 5% and at least
twice the rate of placebo in the total population were somnolence,
dizziness, and nausea.
“We are very pleased with the results of this highly successful
trial in these difficult to treat patient populations with mixed
features in MDD and mixed features in bipolar depression,” said
Dr. Sharon Mates, Chairman and CEO of Intra-Cellular
Therapies. “This study provides proof of concept in these patient
populations and further validates lumateperone’s broad potential in
mood disorders. We look forward to discussing these results with
the FDA and determining next steps for the program.”
“In this study, lumateperone demonstrated a robust effect in
both patients with MDD with mixed features and patients with
bipolar depression with mixed features. This is particularly
significant considering these patients suffer from greater symptom
severity, increased recurrence of mood episodes, higher comorbidity
and increased risk of suicide,” said Stephen Stahl MD, PhD, DSc
(Hon.), Adjunct Professor, Department of Psychiatry, University of
California, San Diego School of Medicine, La Jolla, California and
Clinical Professor of Psychiatry and Neuroscience, University of
California Riverside. “Given the lack of available therapies for
these patient populations, there is a tremendous need for treatment
About Study 403 Study 403 was a randomized,
double-blind, placebo-controlled, global study to evaluate the
efficacy and safety of lumateperone as monotherapy
treatment for patients with major depressive episodes associated
with MDD or Bipolar I or Bipolar II Disorder who also met the
Diagnostic and Statistical Manual of Mental Disorder, 5th Edition
(DSM-5) criteria for mixed-features. Additionally, patients were
required to have a MADRS total score of ≥24, CGI-S of ≥4, and a
Young Mania Rating scale (YMRS) score between 4 and 16.
Patients were randomized 1:1 to lumateperone 42mg (N=192) or
placebo (N=191) with similar distribution between the two
conditions. The primary endpoint of the study was the change from
baseline versus placebo on the MADRS total score at Week 6 and the
key secondary endpoint was the CGI-S which assessed the global
severity of illness.
As initially designed, Study 403 evaluated lumateperone as a
monotherapy treatment for patients with bipolar depression.
Following the successful completion of our bipolar depression
monotherapy and adjunctive program, Study 403 was amended to
evaluate lumateperone as a treatment for patients with MDD with
mixed features and bipolar depression with mixed features. The
results presented above with respect to mixed features exclude the
patients initially enrolled in Study 403 with bipolar depression.
While these patients were diagnostically confirmed for bipolar
depression, they were not diagnostically confirmed for bipolar
depression with mixed features. A sensitivity analysis was
conducted for the total population (ITT N=477) including these
initially enrolled patients and the patients with bipolar
depression with mixed features and patients with MDD with mixed
features. In this pre-specified sensitivity analysis, lumateperone
42mg was statistically significant on the MADRS total score (5.6
point reduction v. placebo; p<0.0001; ES= 0.62) and CGI-S
(p<0.0001; ES= 0.61).
In this study, lumateperone was generally safe and well
tolerated in all patients who received at least one dose of drug,
with a side effect profile consistent with prior lumateperone
trials. Adverse events were mostly mild to moderate and similar to
those seen in prior lumateperone studies in bipolar depression and
About Mixed Features in Bipolar Depression and Major
Depressive DisorderBipolar disorders and major depressive
disorder are highly prevalent serious mental illnesses.
Bipolar disorders affect approximately 11 million adults in
the U.S. and bipolar depression is the most common clinical
presentation of the disorder. Patients with bipolar disorder
generally spend more time in the depressive phase compared to the
MDD affects approximately 21 million adults in the U.S. each
During a current major depressive episode, about one-third of
patients with either bipolar disorder or MDD present with mixed
features. Mixed features is defined by a patient having
co-occurring subthreshold manic symptoms during their depressive
episode or a patient having co-occurring subthreshold depressive
symptoms during their manic episode.
Depressed patients with the presence of mixed features have
greater severity of illness, higher rates of suicidal ideation and
suicide, higher recurrence rates, and higher comorbidities. These
patients are more difficult to treat than patients exhibiting
depressive episodes without mixed features. The inclusion of
the mixed features specifier in DSM-5 underscores the recently
recognized importance of this clinical
presentation.Conference Call and Webcast
DetailsThe Company will host a live conference call and
webcast today at 8:30 AM Eastern Time to discuss the
results of Study 403. To attend the live conference call by phone
please use this registration link. All participants must use
the link to complete the online registration process in advance of
the conference call.
The live and archived webcast can be accessed under "Events
& Presentations" in the Investors section of the Company's
website at www.intracellulartherapies.com. Please log in
approximately 5-10 minutes prior to the event to register and to
download and install any necessary software.
CAPLYTA® (lumateperone) is indicated in adults for the treatment
of schizophrenia and depressive episodes associated with bipolar I
or II disorder (bipolar depression) as monotherapy and as
adjunctive therapy with lithium or valproate.
Important Safety Information
- Elderly patients with dementia-related psychosis
treated with antipsychotic drugs are at an increased risk of death.
CAPLYTA is not approved for the treatment of patients with
- Antidepressants increased the risk of suicidal thoughts
and behaviors in pediatric and young adults in short-term studies.
All antidepressant-treated patients should be closely monitored for
clinical worsening, and for emergence of suicidal thoughts and
behaviors. The safety and effectiveness of CAPLYTA have not been
established in pediatric patients.
Contraindications: CAPLYTA is contraindicated
in patients with known hypersensitivity to lumateperone or any
components of CAPLYTA. Reactions have included pruritus, rash
(e.g., allergic dermatitis, papular rash, and generalized rash),
Warnings & Precautions: Antipsychotic drugs
have been reported to cause:
- Cerebrovascular Adverse Reactions in Elderly Patients
with Dementia-Related Psychosis, including stroke and
transient ischemic attack. See Boxed Warning above.
- Neuroleptic Malignant Syndrome (NMS), which is
a potentially fatal reaction. Signs and symptoms include: high
fever, stiff muscles, confusion, changes in breathing, heart rate,
and blood pressure, elevated creatinine phosphokinase,
myoglobinuria (and/or rhabdomyolysis), and acute renal failure.
Patients who experience signs and symptoms of NMS should
immediately contact their doctor or go to the emergency room.
- Tardive Dyskinesia, a syndrome of uncontrolled
body movements in the face, tongue, or other body parts, which may
increase with duration of treatment and total cumulative dose. TD
may not go away, even if CAPLYTA is discontinued. It can also occur
after CAPLYTA is discontinued.
- Metabolic Changes, including hyperglycemia,
diabetes mellitus, dyslipidemia, and weight gain. Hyperglycemia, in
some cases extreme and associated with ketoacidosis, hyperosmolar
coma or death, has been reported in patients treated with
antipsychotics. Measure weight and assess fasting plasma glucose
and lipids when initiating CAPLYTA and monitor periodically during
- Leukopenia, Neutropenia, and Agranulocytosis (including
fatal cases). Complete blood counts should be performed in
patients with pre-existing low white blood cell count (WBC) or
history of leukopenia or neutropenia. CAPLYTA should be
discontinued if clinically significant decline in WBC occurs in
absence of other causative factors.
- Decreased Blood Pressure & Dizziness.
Patients may feel lightheaded, dizzy or faint when they rise too
quickly from a sitting or lying position (orthostatic hypotension).
Heart rate and blood pressure should be monitored and patients
should be warned with known cardiovascular or cerebrovascular
disease. Orthostatic vital signs should be monitored in patients
who are vulnerable to hypotension.
- Falls. CAPLYTA may cause sleepiness or
dizziness and can slow thinking and motor skills, which may lead to
falls and, consequently, fractures and other injuries. Patients
should be assessed for risk when using CAPLYTA.
- Seizures. CAPLYTA should be used cautiously in
patients with a history of seizures or with conditions that lower
- Potential for Cognitive and Motor Impairment.
Patients should use caution when operating machinery or motor
vehicles until they know how CAPLYTA affects them.
- Body Temperature Dysregulation. CAPLYTA should
be used with caution in patients who may experience conditions that
may increase core body temperature such as strenuous exercise,
extreme heat, dehydration, or concomitant anticholinergics.
- Dysphagia. CAPLYTA should be used with caution
in patients at risk for aspiration.
Drug Interactions: CAPLYTA should not be used
with CYP3A4 inducers. Dose reduction is recommended for concomitant
use with strong CYP3A4 inhibitors or moderate CYP3A4
Special Populations: Newborn infants exposed to
antipsychotic drugs during the third trimester of pregnancy are at
risk for extrapyramidal and/or withdrawal symptoms following
delivery. Breastfeeding is not recommended. Dose reduction is
recommended for patients with moderate or severe hepatic
Adverse Reactions: The most common adverse
reactions in clinical trials with CAPLYTA vs. placebo were
somnolence/sedation, dizziness, nausea, and dry mouth.
CAPLYTA is available in 10.5 mg, 21 mg, and 42 mg capsules.
Please click here to see full Prescribing Information
including Boxed Warning.
About CAPLYTA (lumateperone)
CAPLYTA 42 mg is an oral, once daily atypical antipsychotic
approved in adults for the treatment of schizophrenia and
depressive episodes associated with bipolar I or II disorder
(bipolar depression) as monotherapy and as adjunctive therapy with
lithium or valproate. While the mechanism of action of CAPLYTA is
unknown, the efficacy of CAPLYTA could be mediated through a
combination of antagonist activity at central serotonin 5-HT2A
receptors and postsynaptic antagonist activity at central dopamine
Lumateperone is being studied for the treatment of major
depressive disorder, and other neuropsychiatric and neurological
disorders. Lumateperone is not FDA-approved for these
About Intra-Cellular Therapies
Intra-Cellular Therapies is a biopharmaceutical company
founded on Nobel prize-winning research that allows us to
understand how therapies affect the inner-workings of cells in the
body. The company leverages this intracellular approach to develop
innovative treatments for people living with complex psychiatric
and neurologic diseases. For more information, please
This news release contains "forward-looking statements" within
the meaning of the Private Securities Litigation Reform Act of 1995
that involve risks and uncertainties that could cause actual
results to be materially different from historical results or from
any future results expressed or implied by such forward-looking
statements. Such forward-looking statements include statements
regarding, among other things, our plans to discuss the results of
Study 403 with the FDA; whether clinical trial results will be
predictive of future real-world results; whether CAPLYTA will serve
an unmet need; the goals of our development programs; our beliefs
about the potential utility of our product candidates; and
development efforts and plans under the caption “About
Intra-Cellular Therapies.” All such forward-looking statements are
based on management's present expectations and are subject to
certain factors, risks and uncertainties that may cause actual
results, outcome of events, timing and performance to differ
materially from those expressed or implied by such statements.
These risks and uncertainties include, but are not limited to, the
following: there are no guarantees that CAPLYTA will be
commercially successful; we may encounter issues, delays or other
challenges in commercializing CAPLYTA; the COVID-19 pandemic may
negatively impact our commercial plans and sales for CAPLYTA; the
COVID-19 pandemic may negatively impact the conduct of, and the
timing of enrollment, completion and reporting with respect to, our
clinical trials; whether CAPLYTA receives adequate reimbursement
from third-party payors; the degree to which CAPLYTA receives
acceptance from patients and physicians for its approved
indications; challenges associated with execution of our sales
activities, which in each case could limit the potential of our
product; results achieved in CAPLYTA in the treatment of
schizophrenia and bipolar depression following commercial launch of
the product may be different than observed in clinical trials, and
may vary among patients; any other impacts on our business as a
result of or related to the COVID-19 pandemic; challenges
associated with supply and manufacturing activities, which in each
case could limit our sales and the availability of our product;
impacts on our business, including on the commercialization of
CAPLYTA and our clinical trials, as a result of the conflict in
Ukraine; risks associated with our current and planned clinical
trials; we may encounter unexpected safety or tolerability issues
with CAPLYTA following commercial launch for the treatment of
schizophrenia or bipolar depression or in ongoing or future trials
and other development activities; our other product candidates may
not be successful or may take longer and be more costly than
anticipated; product candidates that appeared promising in earlier
research and clinical trials may not demonstrate safety and/or
efficacy in larger-scale or later clinical trials or in clinical
trials for other indications; our proposals with respect to the
regulatory path for our product candidates may not be acceptable to
the FDA; our reliance on collaborative partners and other third
parties for development of our product candidates; and the other
risk factors detailed in our public filings with the Securities and
Exchange Commission. All statements contained in this press release
are made only as of the date of this press release, and we do not
intend to update this information unless required by law.
Intra-Cellular Therapies, Inc.
Juan Sanchez, M.D. Vice President, Corporate Communications and
Burns McClellan, Inc.Cameron
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