BioPharma

FDA approves J&J’s Spravato as first novel antidepressant in decades

The drug, a reformulation of ketamine, was approved for patients who have failed on other antidepressants. The original form of ketamine, approved as an anesthetic, has long been explored as a treatment for depression.

Text FDA Approved appearing behind ripped brown paper.

A formulation of the drug ketamine has received Food and Drug Administration approval as the first treatment for depression with a new mechanism of action in decades.

New Brunswick, New Jersey-based Johnson & Johnson’s Janssen subsidiary announced the approval of Spravato (esketamine), a nasal spray, for treatment of major depressive disorder in patients who have failed on treatment with other antidepressants. The approval of the drug follows a vote to recommend approval last month by the FDA’s Psychopharmacologic Drugs Advisory Committee. Of 17 members, 14 voted in favor of recommending approval, two voted against, and one abstained.

Spravato is a form of ketamine, originally approved in the 1970s and used as an anesthetic. It has also been abused due to its ability to induce dissociative states and is often known by names such as “Special K.” Like the ketamine sold legally for anesthesia, Spravato is a Schedule III controlled substance, along with opioid painkillers, due to the potential for abuse leading to dependence. Still, ketamine has long been explored as a potential treatment for depression due to its ability to relieve symptoms within hours.

Spravato’s label carries a boxed warning with a Risk Evaluation and Mitigation Strategy about the risk of suicidal thoughts and behaviors in children and young adults.

The approval was based on two of four Phase III clinical trials showing a statistically significant superiority of Spravato over placebo, one that measured the short-term efficacy of the drug and another that measured long-term efficacy.

The other two trials did not show statistically significant improvements over placebo. In a briefing document released ahead of the advisory committee meeting, members expressed concern that because patients in one of the trials receiving Spravato at 84mg did not experience greater efficacy than those receiving 56mg, there may be insufficient evidence to say the higher dose yields a therapeutic dose response relative to its higher rate of adverse side effects. That trial’s results did not confirm the relationship between dose and response that had appeared in an earlier Phase II study, the committee members wrote.

For the other study that was not successful, among elderly patients, the committee members expressed concerns about data integrity. They pointed to reported trial protocol violations, discrepancies between locked data sets and an unusual response curve shift, whereby a nearly significant treatment effect emerged 28 days following initiation of treatment, when for three weeks there was no difference, and the other studies showed an effect after only two days.

Photo: Michail_Petrov-96, Getty Images

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