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First Novel Drug Mechanism Approved for Major Depression in Decades; FDA Approves Fast-Acting SPRAVATO™ (Esketamine, Derivative of Ketamine) Nasal Spray for Adults with Treatment-Resistant Depression

On March 5, 2019, Janssen Pharmaceutical Companies of Johnson & Johnson announced that the U.S. Food and Drug Administration (FDA) has approved SPRAVATO™ (esketamine, a derivative of ketamine) CIII nasal spray for use, in conjunction with one of a number of existing oral antidepressant, in adults with treatment-resistant depression (TRD). People who are currently struggling with major depressive disorder (MDD) are considered to have TRD if they have not responded adequately to at least two different antidepressants of adequate dose and duration in the current depressive episode. It is estimated that approximately one-third of U.S. adults with MDD have TRD. "It was hard to have any emotions, because I was just numb," said Robin P., an esketamine clinical trial patient. "When I began treatment with esketamine and my symptoms started to lift, I could see very clearly just how depressed I had been. I'm now able to appreciate a wider range of emotions than when I was depressed. My long-term goals have taken shape and actually seem attainable." Esketamine is the s-enantiomer of ketamine. Ketamine is a mixture of two enantiomers (mirror-image molecules). This is the first FDA approval of esketamine for any use. The FDA approved ketamine (Ketalar) in 1970. "SPRAVATO™ has the potential to change the treatment paradigm and offer new hope to the estimated one-third of people with major depressive disorder who have not responded to existing therapies," said Mathai Mammen, MD, PhD, Global Head, Janssen Research & Development, LLC. "This unique and innovative medicine is a testament to Janssen's heritage of advancing solutions in neuroscience to heal minds and improve health outcomes."

"Depression is a common and potentially debilitating illness that can have profound emotional, functional, and economic impact on both those who suffer and their loved ones. The impact of depression is greatest for those who do not benefit from standard treatments," said Michael E. Thase, MD, a Professor of Psychiatry and Director of the Mood and Anxiety Disorders Treatment and Research Program in the Perelman School of Medicine at the University of Pennsylvania, who served as a site principal investigator for the clinical trials. (Dr. Thase has received research support from Janssen and has served as a paid consultant to the company.) "In Phase 3 clinical trials, we saw this therapy provide sustained improvement to patients with treatment-resistant depression."

SPRAVATO™ uses the first new mechanism of action in decades to treat MDD. SPRAVATO™ works on the N-methyl-D-aspartate (NMDA) receptor, an ionotropic glutamate receptor in the brain. The medicine is administered as a nasal spray that is absorbed by the lining of the nasal passages and into the blood stream.
With the approval of SPRAVATO™, comes a new way of treating TRD. Janssen is working quickly to educate and certify treatment centers in accordance with the REMS (Risk Evaluation and Mitigation Strateies) so healthcare providers can offer SPRAVATO™ to appropriate patients. Later this month, patients can visit www.SPRAVATO.com for a locator tool and to sign up to receive alerts when new treatment centers are available. More locations will be added over time as new treatment centers become certified.

SPRAVATO™ carries a Boxed WARNING regarding a Risk Evaluation and Mitigation Strategy (REMS) and the risk of suicidal thoughts and behaviors in pediatric patients and young adults. See below for Important Safety Information. SPRAVATO™ was studied in a robust Phase 3 clinical trial program with more than 1,700 adults with TRD. In a short-term study, those who took SPRAVATO™, and an oral antidepressant, experienced superior improvement in depression symptoms at four weeks, compared to those who received a placebo and an oral antidepressant. In a long-term study, patients in stable remission taking SPRAVATO™ who continued treatment with the medicine were 51 percent less likely to relapse versus those who maintained a regimen of a placebo and an oral antidepressant.

In the clinical trials, the most common side effects of SPRAVATO™, when used along with an antidepressant taken by mouth, included: dissociation, dizziness, nausea, sedation, spinning sensation, reduced sense of touch and sensation, anxiety, lack of energy, increased blood pressure, vomiting, and feeling drunk.
Once SPRAVATO™ is determined as an appropriate treatment option, in accordance with the REMS, the patient will be treated at a certified treatment center that is trained to administer the medicine and address patient needs.

SPRAVATO™ will not be dispensed directly to patients for home use. Instead, SPRAVATO™ will be self-administered by the patient under the direct observation of a healthcare provider. The healthcare provider will then observe the patient for treatment-emergent sedation, dissociation, and blood pressure changes for at least two hours, until the patient is safe to leave. Patients should not drive or operate heavy machinery until the next day, following a restful sleep. All patients will be enrolled in the SPRAVATO™ REMS registry to further characterize the risks of serious adverse outcomes from sedation, dissociation, abuse and misuse, and to support safe use of this medicine.

Janssen CarePath offers a comprehensive support program that helps patients get started on SPRAVATO™ and stay on track. Janssen CarePath provides information on insurance coverage, potential out-of-pocket costs, and treatment support, and identifies options that may help make treatment more affordable, including the Janssen CarePath Savings Program for commercially insured patients who are eligible.
TREATMENT-RESISTANT DEPRESSION

Approximately one-third of people who have major depressive disorder (MDD) have not responded adequately to at least two different antidepressants of adequate dose and duration in the current depressive episode and are considered to have treatment-resistant depression (TRD). TRD is a chronic condition that places an ongoing emotional, functional, and economic burden on the individual, their loved ones, and society.

Depression may lead to an inability to manage life's demands and maintain social connections, affecting all aspects of one's life, from school and employment, to relationships and overall quality of life. TRD is associated with greater morbidity, higher healthcare costs, and various co-morbid conditions.

SPRAVATO™ CLINICAL PROGRAM

SPRAVATO™ was studied in five pivotal Phase 3 trials in more than 1,700 adults with TRD, including but not limited to a short-term study and one long-term maintenance study. SPRAVATO™ was also studied in four Phase 2 studies and 19 Phase 1 studies in patients with TRD and healthy volunteers. Patients who participated in the double-blind Phase 3 studies received SPRAVATO™ or a placebo in addition to a newly initiated oral antidepressant at the start of the treatment phase.

WHAT IS SPRAVATO™?

SPRAVATO™ is a prescription medicine, used along with an existing antidepressant taken by mouth, for 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. The U.S. FDA granted Breakthrough Therapy designation for SPRAVATO™ for treatment-resistant depression.

PHASE 3 CLINICAL TRIALS UNDERWAY FOR MDD WIT IMMINENT RISK OF SUICIDE

Janssen is also investigating the medicine for a second indication, major depressive disorder with imminent risk for suicide. Janssen is currently conducting Phase 3 clinical studies for the second indication. Janssen submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for the esketamine treatment-resistant depression indication in October 2018 and anticipates approval later in 2019.

Please see links to Jannsen and FDA press releases, and popular news stories in major media, below.

NY Times headline is "Fast-Acting Depression Drug, Newly Approved, Could Help Millions." Washington Post headline is "In Biggest Advance for Depression in Years, FDA Approves Novel Treatment for Hardest Cases."

[Jannsen press release] [FDA press releae]

[Washington Post article] [NY Times article] [USA Today article] [NPR article] [CNBC article] [US News & World Report article]