- A first-of-its-kind treatment for depression got a big nod on Tuesday from a group of scientists convened by the US Food and Drug Administration.
- Experts concluded that the drug, called esketamine and inspired by ketamine, is safe and effective and said its benefits outweighed its risks.
- Their input will play a key role in the FDA’s final approval decision, expected in March.
- If given the official green light, the drug would be the first novel therapeutic for depression in 35 years.
A drug inspired by ketamine, which has been called "the most important discovery in half a century," is on the cusp of becoming the first new kind of depression medication in 35 years.
Called esketamine and developed by Johnson & Johnson, the drug is a nasal spray designed to treat severe forms of depression that don’t respond to other medications. It’s the chemical mirror image of ketamine and thought to have slightly fewer side effects than the original compound.
On Tuesday, a panel of experts convened by the Food and Drug Administration voted 14-2 in favor of the drug’s effectiveness and 15-2 in favor of its safety. Their recommendation will play a key role in the FDA’s approval decision, expected in March.
Additionally, they voted 14-2 that the drug’s benefits outweighed its risks.
"I think there’s substantial evidence that this could be a game-changer," Steven Meisel, a system director of medication safety with Fairview Health Services who was one of the panel’s 17 voting members, said on Tuesday.
If the FDA approves the drug, it would be the first federally approved depression drug in nearly four decades to work differently than depression medications on the market.
Analysts are hopeful that Johnson & Johnson’s new drug could help.
"Ultimately, we think [esketamine’s] risk-benefit profile favors approval, especially in a disease paradigm where little options are available," Carter Gould, the executive director of biotech equity research at UBS, wrote in a note circulated last week.
The emerging science on ketamine
Whether it’s Abilify or Zoloft, almost all antidepressants work by plugging up the places where our brain takes up serotonin, a chemical messenger that plays a key role in our mood.
Ketamine appears to engage a different part of the brain than traditional antidepressants, which is part of the reason it’s been called "the most important discovery in half a century" for mental illness.
The drug’s apparent rapid-fire effects may be especially useful for staunching suicidal thinking in people who are considering taking their own lives, experts say. Ketamine also has long been used to prevent pain, which suggests to clinicians that it’s relatively safe.
"There is nothing approved that gets patients better this fast," Walter S. Dunn, a psychiatrist and assistant clinical professor at the University of California Los Angeles who was also one of the panel’s voting members, said on Tuesday.
But right now, ketamine is neither cheap nor quick to administer. Because it’s given through an IV drip, the process can take 45 minutes to two hours. Each session costs $500 to $750 and is not covered by insurance, because ketamine is approved in the US only for use as an anesthetic. People given ketamine for depression are typically advised to get eight to 12 sessions, bringing the total cost to as much as $9,000.
Ketamine and esketamine also have some negative side effects. The most troublesome, according to analysts and scientists, is the drugs’ tendency to produce what’s known as dissociative — or "out of body" — experiences.
Experts worry that some patients could react negatively to the experience and then avoid the drug, or react positively and want to repeatedly use it, potentially leading to a drug-use disorder. Experts on the FDA panel said no misuse or abuse was seen in Johnson & Johnson’s clinical trials, however, adding that they considered the risk of abuse among adults to be low.
Johnson & Johnson’s nasal spray for depression
Johnson & Johnson’s formulation of esketamine is designed to be taken as a nasal spray alongside a traditional antidepressant, reducing the time required to administer the treatment and potentially making it less expensive. (The company has not said how much the drug could cost.)
The company’s clinical-trial data suggests that the drug is fairly safe and well tolerated but still has some negative side effects.
More than a third of patients in two of Johnson & Johnson’s last-phase clinical trials reported dissociation. To address that, researchers say, the drug should be given in the presence of a clinician who can monitor the person for at least two hours after treatment. Roughly a third of patients in the trials reported dizziness, sedation, or nausea.
Also, because the studies focused on people with severe forms of depression that don’t respond to other medications, suicide was a known risk among the participants. In Johnson & Johnson’s trials, at least three patients died by suicide. On Tuesday, experts said these deaths were not likely a direct result of esketamine — if anything, they could have occurred because it didn’t work well enough, said Qi Chen, an FDA safety reviewer on the panel.
Julie Zito, a pharmacy professor at the University of Maryland who was one of two people who voted against esketamine’s effectiveness, said she didn’t see enough evidence of substantial improvement in mood among the clinical-trial participants.
Other researchers on the FDA panel said the drug still appeared to be more convenient than available antidepressants and the IV version of esketamine because the nasal spray doesn’t require an IV and could be given as frequently as once a week.
Esketamine also appeared to work better than a placebo in people with severe forms of depression over a month. However, the latest clinical trial — one of five studies presented to the FDA — was not able to show that the drug was statistically superior to a placebo. That’s a key finding that other trials appeared to support.
For a study published last May, Johnson & Johnson’s neuroscience partner, Janssen Research, had nearly 240 adults with severe depression take a traditional antidepressant plus a nasal spray for a month. Half got a spray with Johnson & Johnson’s drug, while the other half got a placebo spray. Those results were promising: The people who got the esketamine spray saw significantly better improvements in their depressive symptoms than those who got the placebo.
The month before, researchers did a small, daylong version of the study and came away with similar results. But the latest study, of nearly 350 adults, did not show numbers statistically significant enough to bolster the other findings.
Nevertheless, most of the experts on the FDA-assembled committee said they considered the drug an effective treatment for severe depression. Some said the latest study still suggested positive results even though the findings didn’t reach statistical significance.
"I was persuaded not only by the two positive trials but even by the partial evidence in the third trial that was at least pointing in the same direction," Wilson Compton, the deputy director of the National Institute on Drug Abuse with the National Institutes of Health, said on Tuesday.
from SAI https://read.bi/2S5AuZr