1 Boring Old Man

Before launching in to the ins and outs of Viibryd‘s march to market, I thought it would be important to talk about what’s happening out there in my front yard. This weekend, we drove up to Tennessee to a Craft Fair. It was Tennessee [my birth State] at its best. Driving back Sunday on as fine a day as ever was, I was awed as I always am at the beauty of Fall and feeling nostalgic for the Tennessee of my childhood, but when I got home and looked off the steps of my porch, Fall was there too. I expect there’s some lesson in that story, but I’ll pass on figuring it out and move on the the story of Viibryd and its circuitous route to FDA approval and final release into wide world.

^{The studies in support of this application were conducted under IND 54613. Several meetings were held with the various sponsors over the course of its development. The IND has been held by several different sponsors over its long course. The IND was initially submitted 11-21-97. An early EOP2 meeting was held with the sponsor on 12-20-05, however, this was clearly premature. This meeting focused on a proposed design for the first phase 3 study. Subsequent meetings were held on 8-7-06, 8-20-07, and 5-11-09. The 8-7-06 meeting was another early meeting to discuss CMP, OCP, and pharm/tox issues. The 8-20-07 meeting was focused on their genetic analysis plan, since at that time the sponsor hoped to utilize biomarkers in their development program. The 5-11-09 meeting was to discuss their second phase 3 study and again their plans for genetic analyses. A preNDA meeting was planned for June, 2009, however, this was cancelled since the sponsor found our preliminary comments sufficient to answer all of their questions. Ultimately, they dropped their plans to include analyses of genetic data as part of this NDA.}

It looks as if it was initially patented by Merck in the mid 1990s:

"It was later discovered that patients exhibiting a specific genetic biomarker responded better to treatment with vilazodone. The drug was then licensed to Genaissance Pharmaceuticals, a company specializing in pharmacogenomic therapies, or ‘personalized medicine’. Genaissance then began additional Phase II trials in only those patients exhibiting the desired biomarker."

A Randomized, Double-Blind, Placebo Controlled Study Assessing the Efficacy and Safety of Vilazodone and Discovering Genetic Markers Associated With Response in Patients With Major Depressive Disorder

Genotype data were available for assessment of the relationships between genetic variations in CYP2C19, CYP2D6, and ACE with vilazodone response in the two phase 3 studies. There were no meaningful associations with MADRS by responder analyses or change at 8 weeks. There were also no robust associations with discontinuation rates or failure to reach target dose that could explain the similar responses in CYP2C19 UMs and PMs. Genotype data were not available for all pivotal studies in which DNA was collected. Given the complicated vilazodone metabolic pathway, it is uncertain whether genetic variation on pharmacokinetic-related genes would likely result in clinically meaningful differences in either response or adverse events.

Clinical Data Announces FDA Approval of Viibryd(TM) (vilazodone HCl) for Major Depressive Disorder
1/24/2011

^{NEWTON, Mass.–(BUSINESS WIRE)– Clinical Data, Inc. (NASDAQ:CLDA – News), today announce}d that the U.S. Food and Drug Administration (FDA) has approved vilazodone HCl tablets, to be marketed under the brand name Viibryd™, for the treatment of adults with major depressive disorder (MDD). Viibryd is a new molecular entity and the first and only selective serotonin reuptake inhibitor and 5HT1A receptor partial agonist. Clinical Data plans to make Viibryd available in U.S. pharmacies in the second quarter of this year. "When treating MDD, our goal is to offer treatment options that meet the individual needs of each patient,” said Stephen M. Stahl, M.D., Ph.D., Professor of Psychiatry, University of California, San Diego. “Viibryd is an important new treatment option with proven efficacy and a demonstrated safety profile.”

The mechanism of the antidepressant effect of Viibryd is not fully understood but is thought to be related to its enhancement of serotonergic activity in the central nervous system (CNS) through selective inhibition of serotonin reuptake. Viibryd is also a partial agonist at serotonergic 5HT1A receptors; however, the net result of this action on serotonergic transmission and its role in Viibryd’s antidepressant effect are unknown. 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.

Viibryd was demonstrated to be safe in clinical studies. In the placebo-controlled, Phase III studies, the most commonly observed adverse reactions in Viibryd-treated patients were diarrhea, nausea, vomiting and insomnia. No single adverse event led to discontinuation of treatment in greater than 1% of patients. Overall, 7.1% of the patients who received Viibryd discontinued treatment due to an adverse reaction, compared to 3.2% of placebo-treated patients. Viibryd has not been associated with any clinically important changes in laboratory test parameters including liver function tests, ECG including QT interval, or vital signs. In addition, Viibryd had no effect on body weight as measured by mean change from baseline in the 8-week studies. Among the common adverse reactions (=2%) related to sexual function with Viibryd compared to placebo were decreased libido (4% vs. <1%), abnormal orgasm (3% vs. 0%), delayed ejaculation (2% vs. 0%, males only), and erectile dysfunction (2% vs. 1%, males only).

“While there are currently available treatments for MDD, no one therapy works for every patient and side effect profiles vary, which may impact both compliance and treatment success,” said Carol R. Reed M.D., Executive Vice President and Chief Medical Officer of Clinical Data. “Viibryd will be a new choice for healthcare providers and their patients who are suffering from depression.” “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.”

But in February 2011, barely a month after FDA Approval of Viibryd, Forest Laboratories acquired Clinical Data and Viibryd along with it [I expect my rendition of this story is flawed in some temporal details, but it’s the best this old man who still can barely spell business without a dictionary is able to muster]. My point is that Viibryd was not developed and tested by one of the big pharmaceutical companies. It was moved through the Phase 3 Clinical Trials by a series of small entities in the business of genetic testing, and only acquired by Forest Laboratories after FDA Approval.

Is Clinical Data/Forest Labs Deal Bad for Biotech?
Seeking Alpha^a
By M.E. Garza
February 23, 2011

The news that Clinical Data sold to Forest Laboratories  for only $30 a share plus incentives sent some minor shockwaves through the biotech community. It wasn’t that the news wasn’t highly anticipated, in fact, going as far back as 2007, the man who engineered the biotech sale was already polishing CLDA for deals. The thing that left investors scratching their heads was the unexpected $1.2 billion buyout price – $30 a share in cash plus $6 per share more if sales milestones are met – a discount of nearly 12 percent from Friday’s closing price of the stock.

Randal J. Kirk, is the man behind the scenes at CLDA that everyone has been second-guessing for weeks leading up to the deal is the same billionaire who structured a $2.4 billion sale of biotech company Scios Inc. to Johnson & Johnson in 2003 and a $2.6 billion sale of New River Pharmaceuticals to Shire  four years later- both while pocketing a huge chunk of the proceeds along the way. Yes, Kirk has been positioning himself for the windfall from today’s Clinical Data deal for years and just as it did back then, the media attention will now turn to the next company that Kirk has been molding into a more valuable asset – his new synthetic biology company Intrexon. Forbes and others are already calling the venture far bigger than anything Kirk has done before. Kirk predicts the new company will someday be "the Google of the life sciences."

Nobody can fault Kirk, or his method for means and prosperity, but some are left wondering whether the CLDA/FRX deal is good for the rest of the biotech sector given the broad-reaching sentiment that he should have held out for something sweeter. Yes, CLDA was a $14 stock just a few weeks ago, but speculators had hoped for a buy-out somewhere north of $40. In fact, one analyst had even set a price target of $46 per share of Clinical Data stock. After all, the Massachusetts-based biotech had just gotten FDA approval for the antidepressant Vilazodone [marketed as Viibryd], which Kirk himself calls "the first genuinely new antidepressant in 14 or 15 years." The market felt Viibryd offered Big Pharma a very special proposition: The drug does not have the negative impact on sexual associated with most of the current therapies available to those suffering from depression. Those rooting for the stock argue that the market potential could be tremendous given that as many as 40% of patients currently taking some of the best-selling depression treatments report sexual side effects, which often leads to discontinuation of therapy. In fact, clinicians observed a slight improvement in sexual function for patients treated with Viibryd, although those improvements did not reach statistical significance. Even Kirk said, "I haven’t spoken to anyone who doesn’t appreciate the differentiation this has."

Theoretically, a big drug company desperate for new products would have offered a better deal. Sources told BioMedReports that some at the company were hoping for a deal with Eli Lilly – who markets Cymbalta- late in the game. Even now, some feel that there is still a window for another firm to come in and top the priced deal, but given his track record and the fact that Kirk is sitting on a 52% stake worth over $600 million (common stock, convertible notes and warrants), it looks to most of us like the dealin’ is done and that Kirk is ready to move on…

Carol R. Reed, M.D. joined Clinical Data in October 2005 as Senior Vice President and Chief Medical Officer following the completion of its merger with Genaissance Pharmaceuticals, Inc., where Dr. Reed had served as Vice President, Medical Affairs since 2003. In April 2008, Dr. Reed was appointed Executive Vice President and Chief Medical Officer of Clinical Data. Dr. Reed joined Genaissance from Bayer Pharmaceuticals, Inc., where she was an Associate Medical Director in Pulmonary Medical Research. Previously, she was the Associate Director, Section of Pulmonary and Critical Care Medicine, at the Hospital of St. Raphael and directed its Medical Intensive Care Unit. Dr. Reed received a M.S. in biology from the University of Illinois and a M.D. from Rush Medical College in Chicago.

So what happens now? Will our literature be flooded with Forest Laboratory funded articles with the usual suspects signing on as guest authors singing the praises of Viibryd? Will the KOL Speakers Bureaus send out their legions of mercenaries with creative CME programs? Will our television viewing be punctuated with beautiful people recovering from depression, smiling at their new-found sexual prowess? And what of our old friends, the review articles with novel innovative promising new treatments, including Viibryd – maybe even augmenting Viibryd with Latuda?