First Big Depression Advance Since Prozac Nears FDA Approval
The U.S. Food and Drug Administration is on the brink of approving a breakthrough drug that could upend the way severe depression is treated.
Johnson & Johnson’s esketamine, a close chemical cousin of the anesthetic ketamine, cleared a major hurdle on Tuesday when a panel of outside experts recommended that the FDA approve the treatment. The fast-acting antidepressant, administered via a nasal spray, is being tested in major depressive disorder and suicidal thinking. If approved, it would be the first major therapeutic advance for depression since the introduction of Prozac in 1987.
Prozac and other currently available antidepressants take weeks to work and don’t help all patients, so esketamine could mark a significant shift in depression therapy.
The panel voted 14-2 with one abstention that the benefits of the drug and a safety program proposed by the company to keep it from being misused outweigh the risks of abuse.
“I believe esketamine has the potential to be a game-changer in the treatment of depression,” Walter Dunn, a panel member and a psychiatrist at the West Los Angeles Veterans Administration Medical Center, said after the vote. “The rates of response in this treatment-resistant population is better than we’ve seen. The rapid timeline of response is better. There’s nothing approved that gets patients better this fast.”
Amid the opioid addiction and overdose epidemic in the U.S., the panel of experts weighed the abuse potential of ketamine, which at much higher doses is a party drug and can put users into a “k hole” in which they’re unable to interact with the world around them. In a report ahead of the meeting, agency staff called ketamine abuse “relatively uncommon,” with just 1.3 percent of people over age 12 abusing the drug, lower than the abuse rates for other hallucinogens like ecstasy and LSD.
“Ketamine is a nasty drug,” said Steve Meisel, a panel member and system director of medication safety at Fairview Health Services in Minneapolis. “It’s been around for 50 years. Those of us who have seen it used know the adverse-event profile is large.”
But Meisel said he was convinced by a patient survey Johnson & Johnson conducted. “We don’t take the patient voice into account enough,” he said.
Some patients taking esketamine experienced disassociation, an out-of-body experience that the company says cropped up within an hour of treatment and would be monitored in an office setting if it occurs. Some patients also experienced modest spikes in blood pressure during that window.
Esketamine was developed by J&J after a group of researchers discovered that ketamine, an off-patent drug, had a surprisingly rapid antidepressant effect. Some of the first research showing this dates back to the 1990s, and that work was furthered by the National Institutes of Health before being developed into a pharmaceutical treatment by J&J.
J&J plans to call the drug Spravato, it said in a statement following the advisory panel meeting.
“Our comprehensive research program for esketamine nasal spray supports a positive benefit-risk profile for adults with treatment-resistant depression,” said Husseini Manji, global head of the neuroscience therapeutic area at the J&J unit that developed the drug, Janssen Research & Development
Studies have also shown ketamine has the potential to rapidly reduce suicidal thinking, and J&J is studying esketamine for in depressed patients on the verge of killing themselves as well. That data is expected later this year.
The nasal spray is a key part of J&J’s pharmaceutical pipeline, as the company faces flagging sales weighed down by drug-pricing scrutiny and biosimilar competition for one of its biggest drugs, the blockbuster arthritis drug Remicade.
J&J shares gained 1.6 percent to $134.16 in New York on Tuesday.
A decision on whether to allow the drug on the market is expected by March 4. Esketamine has the FDA’s breakthrough-therapy designation in treatment-resistant depression as well as for depressed people at risk of suicide. Rival Allergan Plc is also testing a fast-acting antidepressant, rapastinel, which is about a year behind esketamine in testing.
— With assistance by Robert Langreth