Janssen Submits Supplemental New Drug Application to U.S. FDA for SPRAVATO® (esketamine) CIII Nasal Spray for the Rapid Reduction of Depressive Symptoms in Adults with Major Depressive Disorder Who Have Active Suicidal Ideation with Intent
TITUSVILLE, N.J., Oct. 2, 2019 /PRNewswire/ -- The Janssen Pharmaceutical Companies of Johnson & Johnson today announced the submission of a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) seeking a new indication for SPRAVATO(®) (esketamine) CIII nasal spray for the rapid reduction of depressive symptoms in adult patients with major depressive disorder (MDD) who have active suicidal ideation with intent. The submission is based on results from the Phase 3 ASPIRE I & II trials, which evaluated the efficacy and safety of SPRAVATO(® )versus placebo nasal spray in this high-risk patient population when used in addition to comprehensive standard of care (SOC). In these studies, comprehensive SOC included initial hospitalization and newly initiated and/or optimized antidepressant therapy.(2,3,4)
"This submission is a significant step in helping a vulnerable patient population by providing a potential treatment option to rapidly reduce symptoms of depression in adults with active suicidal ideation with intent, which constitutes a psychiatric emergency that requires immediate intervention," said Husseini K. Manji, M.D., Global Head, Neuroscience Therapeutic Area, Janssen Research & Development, LLC. "It extends our focus on severe manifestations of major depressive disorder beyond the current indication for treatment-resistant depression."
The data from the ASPIRE I & II trials were recently presented at the 32(nd) European College of Neuropsychopharmacology (ECNP), which took place September 7-10 in Copenhagen, Denmark. The double-blind, randomized, placebo-controlled, multicenter studies both met their respective primary efficacy endpoint, which was a reduction in depressive symptoms at 24 hours after the first dose, as measured by the Montgomery-Asberg Depression Rating Scale (MADRS). In both studies, SPRAVATO(®) 84 mg plus SOC showed clinically meaningful and statistically significant superiority (p=0.006) compared to placebo plus SOC in rapidly reducing symptoms of major depressive disorder. In these studies, comprehensive SOC included initial hospitalization and newly initiated and/or optimized antidepressant therapy.(2,3,4)
The treatment difference between the two groups on the secondary endpoint of suicidality was not statistically significant. In the studies both SPRAVATO(®) plus comprehensive SOC and placebo plus comprehensive SOC resulted in improvement in severity of suicidality (a composite endpoint including suicidal ideation and behavior) as measured by the revised Clinical Global Impression of Severity of Suicidality (CGI-SS-R) at 24 hours after the first dose. This may be due to the substantial beneficial effects of comprehensive SOC utilized in the clinical trial, including the immediate impact of inpatient psychiatric hospitalization in diffusing the acute suicidal crisis in patients in both treatment groups.(2,3,4)
The FDA granted Breakthrough Therapy designation to esketamine nasal spray for major depressive disorder with imminent risk for suicide in August 2016(5) and approved SPRAVATO(®) (esketamine) CIII nasal spray, in conjunction with an oral antidepressant, for the treatment of treatment-resistant depression in adults on March 5, 2019.(6)
About the ASPIRE I & II Trials
At 24 hours after the first dose of study medication in ASPIRE I & II, the mean difference observed in the reduction of depressive symptoms between the SPRAVATO(®) plus SOC group and the placebo plus SOC group was 3.8 points and 3.9 points, respectively, as measured by the MADRS total score.(2,3,4)
The effect of SPRAVATO(®) plus SOC on symptoms of major depressive disorder was apparent at four hours after the first dose. Between four hours and 25 days, both the SPRAVATO(®) and placebo groups continued to improve, and the magnitude of difference between the groups generally remained throughout the 25-day double-blind period. In the ASPIRE I & II trials, 54 percent and 47 percent, respectively, of the SPRAVATO(®) plus SOC group achieved remission (MADRS score <= 12) by the end of the double-blind period. The clinical improvement during the double-blind period was maintained over the nine-week follow-up period in both treatment groups, during which time the ongoing oral antidepressant was continued.(2,3,4)
In the ASPIRE I & II trials, SPRAVATO(®) plus SOC was well-tolerated with no new safety signals.(2,3,4) The safety profile observed was consistent across the two Phase 3 studies in patients with major depressive disorder who have active suicidal ideation with intent and with previous studies of SPRAVATO(®) in patients with treatment-resistant depression.(6) In the clinical trials, the most common side effects of SPRAVATO(®) plus SOC were dizziness, dissociation, nausea, somnolence, blurred vision, vomiting, paresthesia, increased blood pressure and sedation.(2,3,4)
About SPRAVATO(®)
SPRAVATO(®) is a non-selective, non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor - an ionotropic glutamate receptor. It has a novel mechanism of action, meaning it works differently than currently available therapies for major depressive disorder.(6,9,10,11,12,13)
SPRAVATO(®) (esketamine) CIII nasal spray is approved in the United States for use in conjunction with an oral antidepressant in adults with treatment-resistant depression (TRD) and has been submitted for health authorities' review for TRD in other markets around the world, including Europe.(6,14 )The FDA granted Breakthrough Therapy designation to esketamine nasal spray for treatment-resistant depression in November 2013 and for major depressive disorder with imminent risk for suicide in August 2016.(5)
About Major Depressive Disorder in Adult Patients Who Have Active Suicidal Ideation with Intent
Major depressive disorder (MDD) affects nearly 300 million people of all ages globally and is the leading cause of disability worldwide.(15) With approximately 17 million adults diagnosed in the U.S., people with MDD experience suffering from a serious, biologically-based disease that has a significant negative impact on all aspects of life, including quality of life and function.(16,17)
About the Janssen Pharmaceutical Companies of Johnson & Johnson
At Janssen, we're creating a future where disease is a thing of the past. We're the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular & Metabolism, Immunology, Infectious Diseases & Vaccines, Neuroscience, Oncology, and Pulmonary Hypertension.
Learn more at www.janssen.com. Follow us at www.twitter.com/JanssenGlobal. Janssen Research & Development, LLC is part of the Janssen Pharmaceutical Companies of Johnson & Johnson.
What is SPRAVATO(®)?
SPRAVATO(®) is a prescription medicine, used along with an antidepressant taken by mouth, for treatment-resistant depression (TRD) in adults.
SPRAVATO(®) is not for use as a medicine to prevent or relieve pain (anesthetic). It is not known if SPRAVATO(®) is safe or effective as an anesthetic medicine.
It is not known if SPRAVATO(®) is safe and effective in children.
IMPORTANT SAFETY INFORMATION
What is the most important information I should know about SPRAVATO
(R)
?
SPRAVATO
(R)
can cause serious side effects, including:
-- Sedation and dissociation. SPRAVATO(R) may cause sleepiness
(sedation), fainting, dizziness, spinning sensation, anxiety, or
feeling disconnected from yourself, your thoughts, feelings, space
and time (dissociation).
-- Tell your healthcare provider right away if you feel like you
cannot stay awake or if you feel like you are going to pass out.
-- Your healthcare provider must monitor you for serious side
effects for at least 2 hours after taking SPRAVATO(R). Your
healthcare provider will decide when you are ready to leave the
healthcare setting.
-- Abuse and misuse. There is a risk for abuse and physical and
psychological dependence with SPRAVATO(R) treatment. Your
healthcare provider should check you for signs of abuse and
dependence before and during treatment with SPRAVATO(R).
-- Tell your healthcare provider if you have ever abused or been
dependent on alcohol, prescription medicines, or street drugs.
-- Your healthcare provider can tell you more about the differences
between physical and psychological dependence and drug
addiction.
-- SPRAVATO
(R)
Risk
Evaluation and Mitigation Strategy (REMS). Because of the risks for
sedation, dissociation, and abuse and misuse, SPRAVATO(R) is only
available through a restricted program called the SPRAVATO(R) Risk
Evaluation and Mitigation Strategy (REMS) Program. SPRAVATO(R) can
only be administered at healthcare settings certified in the
SPRAVATO(R) REMS Program and to patients enrolled in the program.
-- Increased risk of suicidal thoughts or actions. SPRAVATO(R) may
cause worsening of depression and suicidal thoughts and behaviors,
especially during the first few months of treatment and when the
dose is changed. Depression and other serious mental illnesses are
the most important causes of suicidal thoughts and actions. Some
people may have a higher risk of having suicidal thoughts or
actions. These include people who have (or have a family history
of) depression or a history of suicidal thoughts or actions.
-- How can I watch for and try to prevent suicidal thoughts and
actions?
-- Pay close attention to any changes, especially sudden changes, in
mood, behavior, thoughts, or feelings, or if you develop
suicidal thoughts or actions.
-- Tell your healthcare provider right away if you have any new or
sudden changes in mood, behavior, thoughts, or feelings.
-- Keep all follow-up visits with your healthcare provider as
scheduled. Call your healthcare provider between visits as
needed, especially if you have concerns about symptoms.
-- Tell your healthcare provider right away if you have any of the
following symptoms, especially if they are new, worse, or worry
you:
--
attempts to commit suicide --
worsening depression
--
thoughts about suicide or dying -- other unusual changes in behavior or
mood
SPRAVATO
(R)
is not for
use in children.
Do not take SPRAVATO(®) if you:
-- have blood vessel (aneurysmal vascular) disease (including in the brain,
chest, abdominal aorta, arms and legs)
-- have an abnormal connection between your veins and arteries
(arteriovenous malformation)
-- have a history of bleeding in the brain
-- are allergic to esketamine, ketamine, or any of the other ingredients in
SPRAVATO(®).
If you are not sure if you have any of the above conditions, talk to your healthcare provider before taking SPRAVATO(®).
Before you take SPRAVATO(®), tell your healthcare provider about all of your medical conditions, including if you:
-- have heart or brain problems, including:
-- high blood pressure (hypertension)
-- slow or fast heartbeats that cause shortness of breath, chest pain,
lightheadedness, or fainting
-- history of heart attack
-- history of stroke
-- heart valve disease or heart failure
-- history of brain injury or any condition where there is increased
pressure in the brain
-- have liver problems
-- have ever had a condition called "psychosis" (see, feel, or hear things
that are not there, or believe in things that are not true).
-- are pregnant or plan to become pregnant. SPRAVATO(®) may harm your
baby. You should not take SPRAVATO(®) if you are pregnant.
-- Tell your healthcare provider right away if you become pregnant
during treatment with SPRAVATO(®).
-- If you are able to become pregnant, talk to your healthcare provider
about methods to prevent pregnancy during treatment with
SPRAVATO(®).
-- There is a pregnancy registry for women who are exposed to
SPRAVATO(®)( )during pregnancy. The purpose of the registry is to
collect information about the health of women exposed to
SPRAVATO(®) and their baby. If you become pregnant during treatment
with SPRAVATO(®), talk to your healthcare provider about
registering with the National Pregnancy Registry for Antidepressants
at 1-844-405-6185 or online at
https://womensmentalhealth.org/clinical-and-research-programs/pregna
ncyregistry/antidepressants/.
-- are breastfeeding or plan to breastfeed. You should not breastfeed
during treatment with SPRAVATO(®).
Tell your healthcare provider about all the medicines that you take, including prescription and over-the-counter medicines, vitamins and herbal supplements. Taking SPRAVATO(®) with certain medicine may cause side effects. Especially tell your healthcare provider if you take Central Nervous System (CNS) depressants, psychostimulants, or Monoamine oxidase inhibitors (MAOIs) medicines.
How will I take SPRAVATO(®)?
-- You will take SPRAVATO(®) nasal spray yourself, under the supervision
of a healthcare provider in a healthcare setting. Your healthcare
provider will show you how to use the SPRAVATO(®) nasal spray device.
-- Your healthcare provider will tell you how much SPRAVATO(®) you will
take and when you will take it.
-- Follow your SPRAVATO(®) treatment schedule exactly as your healthcare
provider tells you to.
-- During and after each use of the SPRAVATO(®) nasal spray device, you
will be checked by a healthcare provider who will decide when you are
ready to leave the healthcare setting.
-- You will need to plan for a caregiver or family member to drive you home
after taking SPRAVATO(®).
-- If you miss a SPRAVATO(®) treatment, your healthcare provider may
change your dose and treatment schedule.
-- Some people taking SPRAVATO(®) get nausea and vomiting. You should not
eat for at least 2 hours before taking SPRAVATO(®) and not drink
liquids at least 30 minutes before taking SPRAVATO(®).
-- If you take a nasal corticosteroid or nasal decongestant medicine take
these medicines at least 1 hour before taking SPRAVATO(®).
What should I avoid while taking SPRAVATO(®)?
Do not drive, operate machinery, or do anything where you need to be completely alert after taking SPRAVATO(®). Do not take part in these activities until the next day following a restful sleep. See "What is the most important information I should know about SPRAVATO(®)?"
What are the possible side effects of SPRAVATO(®)?
SPRAVATO(®) may cause serious side effects including:
-- See "What is the most important information I should know about
SPRAVATO(®)?"
-- Increased blood pressure. SPRAVATO(®) can cause a temporary increase
in your blood pressure that may last for about 4 hours after taking a
dose. Your healthcare provider will check your blood pressure before
taking SPRAVATO(®) and for at least 2 hours after you take
SPRAVATO(®). Tell your healthcare provider right away if you get chest
pain, shortness of breath, sudden severe headache, change in vision, or
seizures after taking SPRAVATO(®).
-- Problems with thinking clearly. Tell your healthcare provider if you
have problems thinking or remembering.
-- Bladder problems. Tell your healthcare provider if you develop trouble
urinating, such as a frequent or urgent need to urinate, pain when
urinating, or urinating frequently at night.
The most common side effects of SPRAVATO(®) when used along with an antidepressant taken by mouth include: dissociation, dizziness, nausea, sedation, spinning sensation, reduced sense of touch and sensation, anxiety, lack of energy, increased blood pressure, vomiting, and feeling drunk.
If these common side effects occur, they usually happen right after taking SPRAVATO(®) and go away the same day.
These are not all the possible side effects of SPRAVATO(®).
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1?800?FDA?1088.
Please see full Prescribing Information, including Boxed WARNINGS, and Medication Guide for SPRAVATO(TM) and discuss any questions you may have with your healthcare provider.
Cautions Concerning Forward-Looking Statements
This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benefits of esketamine. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Research & Development, LLC, any of the other Janssen Pharmaceutical Companies and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; manufacturing difficulties and delays; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended December 30, 2018, including in the sections captioned "Cautionary Note Regarding Forward-Looking Statements" and "Item 1A. Risk Factors," and in the company's most recently filed Quarterly Report on Form 10-Q, and the company's subsequent filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. Neither the Janssen Pharmaceutical Companies nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.
1. Melander H, Salmonson T, Abadie E, et al: A regulatory Apologia--A review
of placebo-controlled studies in regulatory submissions of new-generation
antidepressants. Eur Neuropsychopharmacol 2008;18(9):623-627.
2. Carla Canuso, et al. Esketamine nasal spray for rapid reduction of major
depressive disorder symptoms in patients at imminent risk for suicide:
new data from a global registration program. Presented at European
College of Neuropsychopharmacology (ECNP) congress; September 2019;
Copenhagen, Denmark.
3. Dong-Jing Fu, Carla Canuso, Dawn Ionescu, Xiang Li, Rosanne Lane, Pilar
Lim, David Hough, Wayne Drevets, Husseini Manji. Esketamine nasal spray
for rapid reduction of major depressive disorder symptoms in patients at
imminent risk for suicide: ASPIRE-1 study. Presented at European College
of Neuropsychopharmacology (ECNP) congress; September 2019; Copenhagen,
Denmark.
4. Dawn Ionescu, Carla Canuso, Dong-Jing Fu, Xin Qiu, Rosanne Lane, Pilar
Lim, David Hough, Wayne Drevets, Husseini Manji. Esketamine nasal spray
for rapid reduction of major depressive disorder symptoms in patients at
imminent risk for suicide: ASPIRE-2 study. Presented at European College
of Neuropsychopharmacology (ECNP) congress; September 2019; Copenhagen,
Denmark.
5. Johnson & Johnson Press Release. Esketamine Receives Breakthrough Therapy
Designation from U.S. Food and Drug Administration for Major Depressive
Disorder with Imminent Risk for Suicide. Available at:
https://www.jnj.com/media-center/press-releases/esketamine-recieves-break
through-therapy-designation-from-us-food-and-drug-administration-for-majo
r-depressive-disorder-with-imminent-risk-of-suicide. Accessed August
2019.
6. SPRAVATO(®) [Prescribing Information]. Titusville, N.J., Janssen
Pharmaceuticals, Inc.
7. Montgomery SA, Moller HJ: Is the significant superiority of escitalopram
compared with other antidepressants clinically relevant? Int Clin
Psychopharmacol 2009;24(3):111-118.
8. Melander H, Salmonson T, Abadie E, et al: A regulatory Apologia--A review
of placebo-controlled studies in regulatory submissions of new-generation
antidepressants. Eur Neuropsychopharmacol 2008;18(9):623-627.
9. V Popova, EJ Daly, M Trivedi, K Cooper, R Lane, P Lim, C Mazzucco, D
Hough, ME Thase, RC Shelton, P Molero, E Vieta, M Bajbouj, H Manji, WC
Drevets, JB Singh. Randomized, Double-Blind Study of Flexibly Dosed
Intranasal Esketamine Plus Oral Antidepressant Versus Active Control in
Treatment-Resistant Depression. Poster presented at: 2018 Annual Meeting
of the American Psychiatric Association (APA); May 2018; New York, New
York.
10. EJ Daly, M Trivedi, A Janik, H Li, Y Zhang, X Li, R Lane, P Lim, AR
Duca, D Hough, ME Thase, J Zajecka, A Winokur, I Divacka, A Fagiolini,
WJ Cubala, I Bitter, P Blier, RC Shelton, P Molero, H Manji, WC Drevets,
JB Singh. A Randomized Withdrawal, Double-blind, Multicenter Study of
Esketamine Nasal Spray Plus an Oral Antidepressant for Relapse
Prevention in Treatment-resistant Depression. Poster presented at:
American Society of Clinical Psychopharmacology; May 2018; Miami,
Florida.
11. E Wajs, L Aluisio, R Morrison, EJ Daly, R Lane, P Lim, R Holder, G
Sanacora, AH Young, S Kasper, AH Sulaiman, C Li, J Paik, H Manji, D
Hough, WC Drevets, JB Singh. Long-Term Safety of Esketamine Nasal Spray
Plus an Oral Antidepressant in Patients with Treatment-Resistant
Depression: Phase 3, Open Label Safety and Efficacy Study (SUSTAIN-2).
Poster presented at: The American Society of Clinical Psychopharmacology
Meeting; May 2018; Miami, Florida.
12. M Fedgchin, M Trivedi, EJ Daly, R Melkote, R Lane, P Lim, D Vitagliano,
P Blier, M Fava, M Liebowitz, A Ravindran, R Gaillard, H Ameele, H
Manji, D Hough, WC Drevets, JB Singh. Randomized, Double-Blind Study of
Fixed-Dosed Intranasal Esketamine Plus Oral Antidepressant vs. Active
Control in Treatment-Resistant Depression. Poster presented at: 9th
Biennial Conference of the International Society for Affective Disorders
(ISAD) and the Houston Mood Disorders Conference; September 2018;
Houston, TX.
13. Rachel Ochs-Ross, M.D., Ella J. Daly, MD, Yun Zhang, Ph.D., Rosanne
Lane, M.A.S., Pilar Lim, Ph.D., Karen Foster, B.S., David Hough, M.D.,
Husseini Manji, M.D., Wayne C. Drevets, M.D., Gerard Sanacora, M.D.,
Ph.D., Caleb Adler, M.D., Rupert McShane, M.D., Raphaël Gaillard, M.D.,
Ph.D., Jaskaran B. Singh, M.D. Efficacy and safety of intranasal
esketamine plus an oral antidepressant in elderly patients with
treatment-resistant depression. Poster presented at: American
Psychiatric Association (APA) Annual Meeting; May 2018; New York, NY.
14. Janssen Press Release. Janssen Announces U.S. FDA Approval of
SPRAVATO(®) (esketamine) CIII Nasal Spray for Adults with
Treatment-Resistant Depression (TRD) Who Have Cycled Through Multiple
Treatments Without Relief. Available at:
https://www.janssen.com/janssen-announces-us-fda-approval-SPRAVATO®-esk
etamine-ciii-nasal-spray-adults-treatment-resistant. Accessed March
2019.
15. World Health Organization. Depression. Available at:
http://www.who.int/mediacentre/factsheets/fs369/en/. Accessed June 2018.
16. National Institute of Mental Health. Major depression among adults.
https://www.nimh.nih.gov/health/statistics/prevalence/major-depression-a
mong-adults.shtml. Accessed May 16, 2019.
17. Hofmann S et al. Cogn Behav Ther. 2017;46(4):265-286
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