Transcript

Impact of CAPLYTA on depressive symptoms and disease severity

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What was the impact of CAPLYTA on depressive symptoms and disease severity?
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Please see Important Safety Information, including Boxed Warnings regarding increased mortality in elderly patients with dementia-related psychosis at the end of this video.
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Intra-Cellular Therapies, Inc. is sponsoring this video presentation. The speaker is presenting on behalf of the company and has received compensation for these services. The speaker is presenting information that is consistent with FDA guidelines.
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Please see Important Safety Information, including Boxed Warnings, and full Prescribing Information via the link adjacent to this video player.

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Heather Luing, MD
Medical Director
Florida Center for TMS
Medical Director, Mental Health Unit
Flagler Hospital
St Augustine, Florida

(Dr. Heather Luing)
CAPLYTA demonstrated improvement in depressive symptoms and disease severity in adult patients with bipolar I and bipolar II, when used as monotherapy and as adjunctive therapy with lithium or valproate.
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Demonstrated improvement in depressive symptoms and disease severity in adult patients with bipolar I and bipolar II, when used as monotherapy and adjunctive therapy with lithium or valproate

(Dr. Heather Luing)
Let's consider the data on depressive symptoms across the monotherapy and adjunctive therapy trials. In the monotherapy trial, the impact of CAPLYTA on depressive symptoms was evaluated based on the least squares, or LS, mean change in the MADRS total score from baseline to week 6; this was the primary efficacy endpoint. The LS mean change from baseline in the MADRS total score was minus 16.7 and minus 12.1 with CAPLYTA 42 mg and placebo, respectively.
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Primary Endpoint: LSM Change From Baseline in MADRS Total Score^1-3,a
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-16.7 CAPLYTA 42 mg
P<0.0001 vs placebo
-12.1 Placebo

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LSM, least mean squares; MADRS, Montgomery-Åsberg Depression Rating Scale.
^aStudy 1 placebo-subtracted difference was -4.6 (95% CI, -6.3 to -2.8); mean baseline MADRS total scores for CAPLYTA 42 mg and placebo were 30.8 and 30.3, respectively. There was a 40% improvement from baseline in the placebo group.^1,3
1. Caplyta. Prescribing information. Intra-Cellular Therapies; 2022. 2. Data on File. Intra-Cellular Therapies. 3. Calabrese JR et al. Am J Psychiatry. 2021;178(12);1098-1106.

(Dr. Heather Luing)
There was a 54% improvement from baseline to week 6 with CAPLYTA.
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54% Improvement from baseline^1-3,a

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^aStudy 1 placebo-subtracted difference was -4.6 (95% Cl, -6.3 to -2.8); mean baseline MADRS total scores for CAPLYTA 42 mg and placebo were 30.8 and 30.3, respectively. There was a 40% improvement from baseline in the placebo group.^1,3
1. Caplyta. Prescribing information. Intra-Cellular Therapies; 2022. 2. Data on File. Intra-Cellular Therapies. 3. Calabrese JR et al. Am J Psychiatry. 2021;178(12):1098-1106.

(Dr. Heather Luing)
Additionally, looking at post-baseline reduction in MADRS total score over time, we can see that CAPLYTA separated from placebo as early as week 1, continuing to week 6. It is important to note that the weekly time points prior to week 6 were not powered for statistical comparison and are descriptive only.
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Week 1 → Week 6^1,2
The weekly time points prior to week 6 were not powered for statistical comparison and are descriptive only.^1,2

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1. Caplyta. Prescribing information. Intra-Cellular Therapies; 2022. 2. Data on File. Intra-Cellular Therapies.

(Dr. Heather Luing)
Furthermore, with CAPLYTA, there was also improvement observed across all individual MADRS item scores in monotherapy at week 6. These are exploratory endpoints, so results require cautious interpretation.
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Improvement Across All Individual MADRS Item Scores^a
✔ Reported Sadness ✔ Reduced Appetite ✔ Inability to Feel
✔ Apparent Sadness ✔ Concentration Difficulties ✔ Pessimistic Thoughts
✔ Inner Tension ✔ Lassitude ✔ Suicidal Thoughts^b
✔ Reduced Sleep
Limitation: These secondary endpoints were not powered for statistical comparison and are descriptive only. Therefore, the results require cautious interpretation.

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^aLSM change from baseline on individual MADRS items scored 0-6.
^bPatients who were at risk for suicide were excluded from the clinical trials.
Data on File. Intra-Cellular Therapies.

(Dr. Heather Luing)
Now, let's look at the efficacy data from the adjunctive therapy trial. Prior to enrollment, patients were on a stable therapeutic dose of lithium or valproate and were experiencing inadequate therapeutic response for their depressive symptoms. When CAPLYTA was added to lithium or valproate, the LS mean change in MADRS total score from baseline was minus 16.9 versus minus 14.5 with placebo plus lithium or valproate.
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LSM Change From Baseline in MADRS Total Score^1,2,a
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-16.9 CAPLYTA 42 mg + lithium or valproate
P=0.0206 vs placebo
-14.5 Placebo + lithium or valproate

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^aStudy 2 placebo-subtracted difference was -2.4 (95% CI, -4.4 to -0.4); mean baseline MADRS total scores for CAPLYTA 42 mg and placebo were 32.2 and 32.1, respectively. There was a 45% improvement from baseline in the placebo + lithium or valproate group.^1,2
1. Caplyta. Prescribing information. Intra-Cellular Therapies; 2022. 2. Data on File. Intra-Cellular Therapies.

(Dr. Heather Luing)
There was a 52% improvement from baseline to week 6 with CAPLYTA when added to lithium or valproate.
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52% Improvement from baseline^1,2,a

(Dr. Heather Luing)
CAPLYTA also showed an impact on disease severity, providing a significant improvement in severity versus placebo at 6 weeks, as measured by the LS mean change from baseline in the Clinical Global Impression-Bipolar-Severity of Illness, or CGI-BP-S total score, a key secondary endpoint in the monotherapy trial. The CGI-BP-S total score is a well-established research rating tool measuring the clinician's overall impression of the patient. The LS mean change in CGI-BP-S total score from baseline was minus 3.5 and minus 2.5 for CAPLYTA 42 mg and placebo, respectively.
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Key Secondary Endpoint: LSM Change From Baseline in CGI-BP-S Total Score^1-3,a,b
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-3.5 CAPLYTA 42 mg
P<0.0001 vs placebo
-2.5 Placebo

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CGI-BP-S, Clinical Global Impression-Bipolar-Severity of Illness scale.
^aThe CGI-BP-S total score is based on a clinician-rated scale that measures the patient's current illness state on a 21-point total scale that assesses depression, mania, and overall illness; a higher score is associated with greater illness severity.^1,3
^bStudy 1 placebo-subtracted difference was -0.9 (95% CI, -1.37 to -0.51); mean baseline CGI-BP-S total scores for CAPLYTA 42 mg and placebo were 10.3 and 10.2, respectively.
1. Data on File. Intra-Cellular Therapies. 2. Calabrese JR et al. Am J Psychiatry. 2021;178(12):1098-1106. 3. Caplyta. Prescribing information. Intra-Cellular Therapies; 2022.

(Dr. Heather Luing)
Lastly, in terms of depression severity, CAPLYTA 42 mg with lithium or valproate showed a statistically significant improvement from baseline to week 6 in the CGI-BP-S depression score compared with placebo plus lithium or valproate, as shown here.
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Key Secondary Endpoint: LSM Change From Baseline in CGI-BP-S Depression Score^a
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-1.8 CAPLYTA 42 mg + lithium or valproate
P=0.0082 vs placebo
-1.5 Placebo + lithium or valproate

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^aStudy 2 placebo-subtracted difference was -0.3 (95% CI, -0.59 to -0.09); mean baseline CGI-BP-S depression scores for CAPLYTA 42 mg and placebo were 4.7 and 4.6, respectively.
Data on File. Intra-Cellular Therapies.

(Dr. Heather Luing)
Overall, CAPLYTA demonstrated improvement in depressive symptoms and disease severity in adult patients with bipolar depression, when used as monotherapy and as adjunctive therapy with lithium or valproate.
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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. CAPLYTA, as with other antipsychotic drugs, has a Boxed Warning that elderly patients with dementia-related psychosis treated with antipsychotics are at an increased risk of death. CAPLYTA is not approved for the treatment of patients with dementia-related psychosis. CAPLYTA also has a Boxed Warning that 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.

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), and urticaria.

CAPLYTA has additional warnings and precautions that pertain to the antipsychotic drug class. Patients need to be monitored for the following adverse reactions: cerebrovascular events in elderly patients with dementia-related psychosis; neuroleptic malignant syndrome; tardive dyskinesia; metabolic effects (including hyperglycemia, diabetes, dyslipidemia, and weight gain); leukopenia, neutropenia, and agranulocytosis (including fatal cases); orthostatic hypotension and syncope; falls; seizures; potential for cognitive and motor impairment; body temperature dysregulation; and dysphagia.

Concomitant use of CAPLYTA with CYP3A4 inducers should be avoided. When taking CAPLYTA with strong or moderate CYP3A4 inhibitors, reduce the CAPLYTA dose to 10.5 mg and 21 mg, respectively. The lower dose of 21 mg should also be used in patients with moderate or severe hepatic impairment.

The most common adverse reactions in the schizophrenia clinical trials with CAPLYTA vs placebo were somnolence/sedation and dry mouth. In the bipolar depression clinical trials (as monotherapy and as adjunctive therapy), the most common adverse reactions were somnolence/sedation, dizziness, nausea, and dry mouth.

Please see Important Safety Information, including Boxed Warnings, and full Prescribing Information via the link adjacent to this video player.