A depression drug that’s been called ‘the most important discovery in half a century’ just got a big step closer to FDA approval (JNJ)

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A first-of-its-kind treatment for depression got a big nod from a group of scientists convened by the US Food and Drug Administration on Tuesday.
Experts concluded that the drug, called esketamine and inspired by ketamine, is safe and effective. In addition, they said the drug’s 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. The therapeutic is the chemical mirror image of ketamine and is thought to have slightly fewer side effects than the original compound.

On Tuesday, a panel of outside experts convened by the Food and Drug Administration voted 14-to-2 in favor of the drug’s effectiveness and 15-to-2 in favor of its safety. Their recommendation will play a key role in the FDA’s approval decision for the drug. In addition, they voted 14-to-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 and one of the panel’s 17 voting members, said on Tuesday.

"There is nothing approved that gets patients better this fast," he added.

If the FDA gives final approval — a decision is expected in March — the new drug would be the first federally-approved depression drug to work differently from existing depression medications that have been on the market for nearly four decades.

That’s a significant milestone. Depression is the world’s leading cause of poor health and disability, and as many as one in three patients don’t get relief from current antidepressants.

Analysts are hopeful that J&J’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

Columbia DoctorsWhether it’s Abilify or Zoloft, almost all current antidepressants work by plugging up the places where our brain takes up serotonin, a chemical messenger that plays a key role in mood.

Ketamine appears to engage a different part of the brain from 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 a long history of being used to prevent pain, which suggests to clinicians that it’s relatively safe.

But right now, ketamine is not cheap, and it isn’t quick to administer. Because it’s given by way of an IV drip, the process can take between 45 minutes and two hours. Each session costs $500 to $750 and is not covered by insurance, because ketamine is only approved in the US for use as an anesthetic. Patients given ketamine for depression are typically advised to get 8 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 of these, according to analysts and scientists, is the drugs’ tendency to produce what are known as dissociative, or "out of body," experiences.

Experts worry those effects could lead some patients to react negatively to the experience and then avoid the drug, or react positively to the drug 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 J&J’s clinical trials, however, and added that they considered the risk of abuse among adults to be low.

Johnson & Johnson’s nasal spray for depression

J&J’s formulation of esketamine is designed to be taken by way of a nasal spray alongside a traditional antidepressant, reducing the time required to administer the treatment and potentially making it less expensive as well. (The company has not yet said how much the drug will cost.)

The company’s clinical trial data suggests the drug is fairly safe and well-tolerated, but still has some negative side effects.

The most worrisome of those, according to researchers, is dissocation — an effect that more than a third of patients reported in two of J&J’s last-phase clinical trials. To address that, researchers say the drug should be given in the presence of a clinician who can monitor them for at least 2 hours after treatment. Roughly a third of patients in the trials also reported dizziness, sedation, and nausea.

Also, because the studies focused on a population of people with severe forms of depression that don’t respond to other medications, suicide was a known risk among the participants in the studies. And indeed during the course of J&J’s trials, five patients died by suicide. On Tuesday, experts said these deaths were not likely a direct result of esketamine, however. If anything, they could have occurred because esketamine didn’t work well enough, said Qi Chen, an FDA safety reviewer on the panel.

Julie Zito, a professor of pharmacy at the University of Maryland and 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 also said the drug still appeared more convenient than currently available antidepressants and the IV version of esketamine. That’s because the nasal spray doesn’t require an IV and could be given as infrequently as once a week, they noted.

Esketamine also appears to work better than a placebo in people with severe forms of depression when tested over a month-long period. However, its latest clinical trial — one of five studies it presented to the FDA — was not able to show the drug was statistically superior to a placebo. That’s a key finding that its other trials appeared to support.

For a study published last May, J&J neuroscience partner, Janssen Research, had nearly 240 severely depressed adults take a traditional antidepressant plus a nasal spray for a month. Half got a spray with J&J’s drug; the other half got a placebo spray. Those results were promising: The people who got the real spray saw significantly better improvements in their depressive symptoms than those who got the placebo.

The month prior, researchers did a small, day-long version of this study and came away with similar results. But their latest study of nearly 350 adults did not show statistically significant enough numbers to bolster the previous findings.

Nevertheless, the majority of the FDA-assembled committee considered the drug to be an effective treatment for severe depression. Some people said the last 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.

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Source: Business Insider