FDA Drug Approvals: Back to the Future

The first two new therapies cleared by FDA in 2011 feel like hail from a bygone era: a serotonin inhibitor antidepressant and an angiotensin II blocking anti-hypertensive. This is certainly not how we expected the new drug approval process to work after the FDA Amendments Act was signed into law in 2007.

Our view of the new drug safety law was that it would favor drugs to treat relatively small, high need populations—and especially ones where robust risk management plans could deliver high value to very sick patients. Primary care blockbuster indications? Not so much.

As we like to put it, it will never be 1997 again.

Or will it?

Take the antidepressant Viibryd (vilazodone) and the angiotensin II receptor blocker Edarbi (azilsartan). Both enter crowded primary care classes that seemed vibrant and innovative 15 years ago, but feel saturated and, well, generic today. And both applications breezed through FDA early in 2011, gaining approval on the first cycle, with no deadline extension and no advisory committee review. Just like they probably would have in 1997.

Heck, when Forest acquired Clinical Data, the manufacturer of Viibryd, it felt even more like turning back the clock, with the company that brought Celexa and then Lexapro to market in the 1990s buying back into the class.

And it isn’t just these two drugs. For all the talk that “me too” drugs are out of favor, there have been other recent examples of "me too" success at FDA. Like, for instance, pitavastatin—a statin!—which cruised through FDA in 2009. Or Watson’s Rapaflo, which breezed through in 2008 to provide yet another alpha blocker option for men with BPH.

Those recent approvals are surprising not just for their nostalgic value. They are remarkable as examples of products making it through the agency at a time of chronically dismal new drug approval statistics. Viibryd and Edarbi cleared FDA amid some fairly prominent disappointments for orphan products (Protalix’ Uplyso gets a complete response; Pharming’s Rhucin gets a refuse to file letter), seemingly tougher standards in oncology (think Avastin and TDM-1), and some setbacks for attempts to repurpose old blockbusters for new indications (Contrave for obesity, for example).

What’s going on here?

Okay, first of all, it isn’t 1997 again.

For one thing, even with the two latest approvals, FDA will be lucky to reach half the total in NME/novel biologics for 2011 that it cleared in 1997. FDA approved 44 new molecules that year, compared to just 21 in 2010, and there is no reason to expect a higher total in 2011. (For a comprehensive look at the pending new products in 2011, check out this week's issue of "The Pink Sheet," here.)

And, while the new drugs are coming into huge classes, they don’t exactly have 1997-level blockbuster expectations. Kowa/Lilly’s launch of pitavastin (Livalo) generated just $5.7 million in sales in 2010. That’s just a few hours worth of Lipitor sales. Forest paid $1.2 billion to acquire Clinical Data and Viibryd. That’s a lot of money—but doesn’t exactly suggest anyone things Viibryd will be a billion dollars a year any time soon.

On the other hand, it’s not like other recent launches are doing so great either. Lilly isn’t getting rich on Livalo, but it isn’t getting very far with Effient either--at much higher cost.
And Effient—despite (or perhaps because of?) a massive dataset including a head-to-head comparative trial—struggled through FDA, requiring a protracted review and a public airing of safety questions at an advisory committee, followed by still more internal wrangling over whether and how to address those questions.

Compare that to Edarbi, which went through FDA in 10 months without any public hiccups--and with head-to-head superiority data versus the market leader. It didn’t need an advisory committee, because—as FDA explains in the approval letter—

“This drug is not the first in its class, the safety profile is similar to that of other drugs approved for this indication, the clinical study design is acceptable and similar to previously approved products in the class, evaluation of the safety data [when used in the treatment of hypertension] did not raise significant safety or efficacy issues that were unexpected for a drug of this class, the application did not raise significant public health questions on the role of the drug in the diagnosis, cure, mitigation, treatment, or prevention of a disease, and outside expertise was not necessary; there were no controversial issues that would benefit from advisory committee discussion.”

That may not sound like a ringing endorsement of the products therapeutic potential, but at today’s FDA lack of controversy might be as good as it gets. Commercial models aside, it is just possible that the secret to a first cycle, on time approval is as simple as “me too.”