A month ago I ran across a MEDPAGE TODAY article about Vortioxetine [Brintellix®] and a hearing at the FDA [see indications… and more vortioxetine story…]. Brintellix® had been approved by the FDA for use in Major Depressive Disorder in September of 2014. I had previously run across it through a review article in the Journal of Clinical Psychiatry in December 2014 – a ghost-written garbled affair with multiple KOL guest authors [see the recommendation?…]. It seems that the manufacturers [Takeda and Lundbeck] had been planning for years to try to get it approved for treating the Cognitive Dysfuntion in Major Depressive Disorder. That would be a new category for FDA Approval and would’ve become a strong selling point for this late-coming antidepressant. I found a recent article by Lisa Cosgrove et al who had done a case study of this particular drug and its approval process [Under the Influence: the Interplay among Industry, Publishing, and Drug Regulation] that contained the results of both published and unpublished trials showing that in comparator studies, Brintellix® had uniformly come up short. And I later read a blog on George Dawson’s Real Psychiatry [Vortioxetine] about it.
The NIMH presentation was thoughtful and concluded that the psychometrics being used were not a valid sole proxy for a specific Cognitive Dysfuntion designation.
They had one positive study [FOCUS]. But the second study [CONNECT] didn’t replicate those results. It was reported as statistically significant, but in my opinion, the statistical analysis was flawed.
There’s nothing in my clinical experience or reading that suggests that the affective and cognitive symptoms in depression can be cleanly parsed in this way. Frankly, this felt like a commercially driven ploy.
PRNewswireMar 28, 2016, 20:02 ET
OSAKA, Japan and VALBY, Denmark, March 28, 2016 /PRNewswire/ — Takeda Pharmaceutical Company Limited [Takeda] and H. Lundbeck A/S [Lundbeck] today announced that the U.S. Food and Drug Administration [FDA] issued a complete response letter [CRL] for the supplemental new drug application [sNDA] to include new data in the clinical trials section of the U.S. label of Brintellix® [vortioxetine] for treating certain aspects of cognitive dysfunction in adults with major depressive disorder [MDD]. The FDA approved Brintellix on September 30, 2013 for the treatment of MDD in adults. The CRL does not apply to the use of Brintellix in MDD.Takeda and Lundbeck are disappointed with the response given that the U.S. FDA Psychopharmacologic Drugs Advisory Committee [PDAC] voted 8 to 2 that Takeda and Lundbeck presented substantial evidence to support a claim of effectiveness for Brintellix in treating certain aspects of cognitive dysfunction in adults with MDD. However, the companies were pleased that FDA recognized the importance of cognitive dysfunction in MDD and view it as a legitimate target for drug development…
I don’t nor will I ever know if my letter had anything to do with the FDA’s decision. Other than the average expectable "tree" narcissism ["if a tree falls in the forest and no one hears it, does it make a sound?], I’m not sure I care. I had already gotten my reward from hearing the echo. In another way, I’d actually feel even better if the decision came out this way totally based on the FDA’s own evaluation. Takeda and Lundbeck had gone all out and to a lot of expense trying for this indication [6 cognition-specific clinical trials, bringing a lot of big KOL guns to the IOM workshop and earlier hearing, etc]. I could only guess that the 8:2 vote for Approval was in response to their zeal and presentations. But it just wasn’t in the data, and that’s what the FDA is there to evaluate. So good on them. They did the right thing after all. As for my letter…