Janssen’s Breakthrough Antidepressant Gains Green Light
FDA has approved a Janssen Pharmaceuticals NDA for Spravato (esketamine) nasal spray, in conjunction with an oral antidepressant, for treating depression in adults who have not responded to other antidepressant medicines (treatment-resistant depression). “Because of the risk of serious adverse outcomes resulting from sedation and dissociation caused by Spravato administration, and the potential for abuse and misuse of the drug, it is only available through a restricted distribution system, under a Risk Evaluation and Mitigation Strategy (REMS),” an agency release says.
Spravato is the first therapy in decades approved for patients with major depressive disorder. Its labeling contains a Boxed Warning about sedation risks and difficulty with attention, judgment and thinking (dissociation), abuse and misuse, and suicidal thoughts and behaviors after administration of the drug. “Because of the risk of sedation and dissociation, patients must be monitored by a health care provider for at least two hours after receiving their Spravato dose,” FDA says.
Approval was based on data from three short-term (four-week) clinical trials and one longer-term maintenance-of-effect trial. “In one of the short-term studies, Spravato nasal spray demonstrated statistically significant effect compared to placebo on the severity of depression, and some effect was seen within two days,” FDA says. “The two other short-term trials did not meet the pre-specified statistical tests for demonstrating effectiveness. In the longer-term maintenance-of-effect trial, patients in stable remission or with stable response who continued treatment with Spravato plus an oral antidepressant experienced a statistically significantly longer time to relapse of depressive symptoms than patients on placebo nasal spray plus an oral antidepressant.”
The agency says that the most common side effects were disassociation, dizziness, nausea, sedation, vertigo, decreased feeling or sensitivity (hypoesthesia), anxiety, lethargy, increased blood pressure, vomiting and feeling drunk. “Patients with unstable or poorly controlled hypertension or pre-existing aneurysmal vascular disorders may be at increased risk for adverse cardiovascular or cerebrovascular effects,” it says.
Last month, FDA’s Psychopharmacologic Drug Advisory Committee and Drug Safety and Risk Management Advisory Committee jointly voted 14 to 2 to support Spravato. Panel members said the data showed that Spravato could become a “game changer” for treating depression. They voiced support for its response rates and faster response times compared to current therapies.
Esketamine is a close form of the anesthetic ketamine, which has been previously abused as a party drug. Addressing the abuse potential, FDA reviewers said ketamine abuse is relatively uncommon, with just 1.3% of those over age 12 abusing the drug, which is lower than abuse rates for other hallucinogens like ecstasy and LSD.