At a Jan. 24 news conference, Clinical Data announced that the U.S. Food and Drug Administration (FDA) has approved Viibryd (vilazodone HCl tablets) for the treatment of adults with major depressive disorder (MDD). Clinical Data says that Viibryd will be made available in U.S. pharmacies in the second quarter of 2011.
"Viibryd is the only antidepressant that is a selective serotonin reuptake inhibitor and 5HT1A receptor partial agonist," said Drew Fromkin, President and CEO of Clinical Data. "It is also the first drug that the company has developed, and to have received marketing approval from the FDA on its first review is a significant milestone for Clinical Data."
According to Chief Medical Officer Carol R. Reed, MD, the efficacy of Viibryd as a treatment for MDD was established in two 8-week, multicenter, randomized, double-blind, placebo-controlled studies in adults who met the criteria for MDD.
In these studies, patients were titrated over two weeks to a dose of 40 mg of Viibryd once daily. Viibryd was superior to placebo in the improvement of depressive symptoms as measured by the mean change from baseline to week 8 in the Montgomery-Asberg Depression Rating Scale (MADRS) total score.
She adds that Viibryd was demonstrated to be safe in clinical studies, noting that in placebo-controlled, Phase III studies, the most commonly observed adverse reactions in Viibryd-treated patients were diarrhea, nausea, vomiting and insomnia.
Viibryd has not been associated with any clinically important changes in vital tests of liver function, ECG including QT interval, or vital signs. And, it had no effect on body weight (based on mean changes from baseline) in the 8-week studies.
Reed points out that Viibryd is a novel chemistry that differs significantly from SSRIs because it not only inhibits serotonin reuptake, but also is “a very potent and selective agonist for serotonin 1A receptors.” She adds that these receptors “are thought to be especially active in areas of the brain that are believed to control mood.”
The chemistry thus combines the reuptake inhibition of an SSRI with a direct stimulatory effect on the post-synaptic neuron to which it binds. Reed says the net result is thought to be increased serotonin activity.
Viibryd’s novel action and its safety profile data bode well for its sales potential in the $12 billion U.S. market for antidepressants, given the wide range of side effects that individuals may encounter when receiving antidepressant therapy, in particular the sexual side effects associated with many SSRI medications and the weight gain and metabolic concerns associated with a range of antidepression treatments.
FDA: Not enough data to claim fewer sexual side effects
But the most interesting findings in Viibryd studies, and the key to its potential blockbuster impact in the market, aren’t referenced on its new FDA labeling. There’s a difference of opinion between the FDA and the company about data from studies evaluating the impact of vilazodone on sexual function during MDD treatment.
The latest study, whose results were released at the U.S. Psychiatric and Mental Health Congress, concludes that vilazidone’s impact on sexual function is similar to that of placebo. Given that treatment-emergent adverse events (TEAEs), involving sexual function affect 40 percent of those receiving SSRI antidepressant treatment and are a top reason for treatment noncompliance, this is a remarkable claim.
Too remarkable, apparently, for investigators at the FDA. In the company’s news conference, Ross stated, “You may have noticed that our data from quantitiative measures of sexual function are not included in our [new FDA] labeling. In our discussions with FDA, it was determined that these data were not appropriate for the label at this time.”
Sandy Walsh, a spokesperson in the FDA’s public affairs office, consulted with FDA officials and explained, “It's a situation where better data are needed. All we have now are spontaneous reports from controlled clinical studies suggesting there might be some risk of sexual dysfunction, and also some more specific assessments of sexual function in a few controlled trials that show a mixed and difficult-to-interpret picture.
“What is missing—and what is needed—is a well-done, controlled trial including vilazodone, an active comparator [another SSRI] that is known to cause sexual dysfunction (for assay sensitivity), and placebo, and that includes the kinds of specific instruments that are well-accepted (CSFQ or ASEX). It would be up to the drug company to make this investment. The current drug labeling suggests there might be sexual dysfunction.”
Bill Glazer, MD, a veteran researcher who authors Behavioral Healthcare’s Rx Resources column, understood the agency’s caution, commenting, “We’ve seen enough drugs come out where the early promise of a different side effect profile just doesn’t work out.”
He suggested that medication like Viibryd would “likely have to have two positive findings—in head-to head comparison studies with other antidepressants, showing statistically significant differences in the level of sexual dysfunctions.”
Dr. Reed stated that Clinical Data is confident that its data accurately represent the clinical profile of Viibryd and that the company is committed to “additional discussions with the FDA with regard to options for labeling,” however she did not comment on whether the company would proceed with the studies suggested by the FDA.