Their antidepressant is expensive, and it isn’t selling well.
But the drug makers behind the medication are betting they can give it a boost by marketing it to treat a whole new category of depression symptoms — namely, cloudy thinking.
The catch: The Food and Drug Administration must first be persuaded that such symptoms can be treated as a separate category — and that the drug, sold as Brintellix, can treat it.
An FDA advisory committee meets Wednesday morning to debate whether cognitive dysfunction can be pulled out and treated as “a distinct entity,” separate from symptoms like pervasive sadness and apathy. That will set the stage for an afternoon vote on whether the FDA should approve Brintellix as the first treatment for the muddled thinking that often comes along with depression.
Drug makers Takeda Pharmaceuticals and Lundbeck are counting on approvals to create new demand for the drug and new justification to convince insurance companies to pay for it.
But experts say it’s not clear that Brintellix is any more effective than its competitors in making a difference for reversing depression’s cognitive complications.
“Clinically, in talking to my colleagues, we don’t really see any major differences in terms of cognitive effects between Brintellix and other drugs,” said Dr. Norman Sussman, a psychiatrist at New York University’s Langone Medical Center. “We don’t know that Prozac doesn’t do it as well. Or Zoloft. Or any of the other drugs.”
Brintellix, known generically as vortioxetine, was approved in 2013 for treating depression. And in a field dominated by generics, Brintellix stands out mostly for the hefty price tag it carries.
A 30-tablet regimen of the drug went for $290 late last year. Compare that with equivalent dosages of the many off-patent alternatives on the market: a generic version of Prozac sold by Vensun Pharmaceuticals has a $3 price tag, and a generic version of Zoloft sold by Northstar Rx goes for $5. (Those numbers, compiled by the research firm Truven Health Analytics, refer to the price that a manufacturer listed for a drug when it was sold to a wholesaler.)
That price gap has prompted health plans to balk when physicians try to prescribe Brintellix.
Clinicians often face a headache of paperwork demands from insurance companies when seeking justification for a Brintellix prescription, and many plans have formal policies in place to limit them. For example, the Michigan insurer HealthPlus will only cover Brintellix for patients who’ve struggled with dosage levels and have already tried at least three generic antidepressants.
That’s made many psychiatrists reluctant to prescribe Brintellix, or prompted them to only turn to it as a late resort for patients for whom other cheaper drugs have failed.
“I don’t want to start someone on something and know that they’re not going to be able to afford more than a week of it,” said Dr. Christopher Marano, a psychiatrist at Johns Hopkins University School of Medicine who specializes in treating depression in the elderly. “From my perspective, I don’t see any reason to jump right to Brintellix as a first-line agent right now.”
Takeda and Lundbeck’s investment in research to show that Brintellix can effectively treat the cognitive symptoms of depression — including problems with concentration, memory, and processing speed — is an effort to change that attitude among doctors.
Like all antidepressants on the market, Brintellix initially won FDA clearance on the back of studies that focused on mood-related symptoms. But Takeda and Lundbeck also ran two trials looking specifically at cognitive symptoms in patients who took the drug compared to those who took a placebo.
The results of those trials, which involved a total of 1,200 patients with moderate to severe depression, will be under the microscope when the FDA panel of mental health advisors meets this week at the agency’s White Oak Campus in Silver Spring, Md. The FDA doesn’t have to follow the panel’s recommendations, but it usually does. The agency has a deadline of March 28 to make a final decision on the expanded marketing application.
Takeda and Lundeck’s strategy follows a familiar playbook: Drug makers often try to boost sales of existing medications by looking for new indications that could help them stand out from the crowd. (Another typical approach, particularly for companies in the antidepressant market, is to invest in research to make the case that their drug causes fewer side effects than competitors.)
Brintellix appears to provide cognitive benefits, but anecdotal reports suggest that other antidepressants do, too.
But patients with depression and their doctors don’t have a good way to assess whether Brintellix is their best option because no trials — including the ones being used to support Brintellix’s application — have tested drugs head-to-head for their cognitive effects. And the makers of antidepressants that have gone generic have little incentive to invest in the kinds of rigorous clinical studies needed for FDA approval.
Dr. Roger McIntyre, a psychiatrist at the University of Toronto who led one of the trials supporting Brintellix’s FDA application, acknowledged that the lack of direct comparisons was a limitation. But he said he has other reasons to be optimistic about the drug.
Unlike many other antidepressants, which just block the reuptake of serotonin and other neurotransmitters, Brintellix can modulate the proteins that seratonin switches on, a mode of action which has downstream effects on other neurochemical systems. And compared to other antidepressants, Brintellix has more consistently spurred neuronal connections in brain cells when tested in a laboratory setting.
“We do have pieces of the puzzle that provide a robust scientific rationale that would lead us to believe that there’s something unique about this agent at the neurochemical level in the brain,” said McIntyre, who accepts consulting fees, speaking fees, and research support from Takeda, Lundbeck, and some of their competitors.
Neither Takeda nor Lundbeck made an executive available for an interview.
Clinically superior to its competitors or not, a new marketing authorization from the FDA would give Takeda and Lundbeck the ability to advertise Brintellix for that purpose, and to dispatch sales representatives to doctors’ offices to tout that use. Those factors would likely boost prescriptions by psychiatrists looking to help patients with cognitive symptoms — and make it harder for insurers to say no.
“The ammunition will be much stronger for clinicians if there’s a label that supports this drug being different from the others,” said Harry Tracy, a pharmaceutical industry consultant and the publisher of NeuroPerspective, a bimonthly publication focused on treatments for neurological and psychiatric diseases.
But first, the advisory committee that meets Wednesday must be convinced not only that Brintellix works, but also that cognitive dysfunction in depression can even be treated in the first place.
It’s hardly a given. There’s no clear view about how to diagnose depression-induced cognitive dysfunction, or what to measure in designing trials testing drugs that might be able to treat it.
But many patients and their families clearly see an unmet need.
Gary Girton, who suffered from severe depression for most of his life, found relief for years by working in his studio as a mosaic artist. Yet, as the cognitive symptoms of his depression intensified in the last year and a half of his life, it became harder for him to do what he loved.
Remembering where he’d left off on a project, distinguishing spacial elements, and being creative all became more frustrating until he stopped going to his studio. He died by suicide in 2014, at the age of 45.
His widower, Marlin Collingwood, now the executive director of the Massachusetts-based nonprofit Families for Depression Awareness, submitted written testimony that will be considered on Wednesday advocating for greater focus on the cognitive symptoms. (Girton never took Brintellix, and Collingwood won’t take a position on its application.)
“The fact that the FDA and pharma companies are seriously looking at ways to help those people deal with the cognitive side of things” Collingwood said, “is a very important step forward in the treatment of depression.”