If thereâ€™s one piece of pharma news that should come as no surprise, itâ€™s FDA throwing a new drug back at its maker with a â€œTry again later.â€ After all, the agency spent last year handing out â€œapprovableâ€ letters like pharma hands out freebies. Thatâ€™s why weâ€™re surprised that analysts, reporters, and possibly even Merck R&D superstar Peter Kim (right) were all thrown for a loop at the knockdown of Cordaptive, the companyâ€™s biggest â€™08 contender.
(To add insult to that $2 billion blockbuster-to-be injury, the agency even rejected the name Cordaptive. But, hey, Tredaptive is OK! Go figure.)
Why the surprise? Because Merck was so confidentâ€”thatâ€™s why. Believe it or not, thatâ€™s the reason several leading analysts gave to the media on Tuesday. Analysis? Not so much.
In their defense, Cordaptive was approved in Europe only last week. And only last month, FDA OKâ€™d Abbottâ€™s Simcor, a Niaspan
Of course, itâ€™s a dangerous business trying to interpret the mysterious workings of FDA. But since neither the agency nor Merck is talking, the reason for the â€œnot approvableâ€ letter is anybodyâ€™s guess. So get in line.
Businessweek (niacin)/statin combo. And since Cordaptive is also based on high-dose niacin, anyone reading the FDA tea leaves could surmise that the agency is bullish on niacinâ€”currently the only safe and effective way to increase HDL, the â€œgoodâ€ cholesterol.
The Merck drug was a nice piece of innovation: Kimâ€™s elves figured out what causes niacinâ€™s worst side effect, facial flushing, and developed a spanking new chemical, laropiprant, to control it. But since the cholesterol market is not exactly underserved by pharma, you could also surmise that FDA is getting bearish on innovation there (more about that later).â€™s John Carey, apparently the only reporter not to be surprised, offers a must-read analysis of the situation. â€œAdd it all up and the FDA’s decision shouldn’t be seen as coming out of the blue. Cordaptive offers no big improvement over niacin aloneâ€”while introducing a new, unknown risk. And even the benefits of niacin’s effect on cholesterol may not be that big.â€
Cordaptiveâ€™s only potential advantage over Niaspan or generic niacin is the laropiprant, but it cut the rate at which people went off treatment by only a modest 5 percent. As for risks, best guess is that FDA was underwhelmed by Merckâ€™s safety data. Laropiprant works by blocking the hormone prostaglandin, and the agency presumably is asking for better long-term data of its potential dangers. And whether itâ€™s a result of the current Vytorin debacle or the Vioxx disaster, FDA is obviously in no mood to cut Merck any breaks when it says, â€œTrust meâ€ about its data.
According to a post by someone named The Pharmacoepidemiologist at Derek Loweâ€™s blog, In the Pipeline, the NDA for Cordaptive wasnâ€™t up to snuff. It showed elevated liver enzymesâ€”a major post-Vioxx red flagâ€”and contained no mortality data at all. (Missing data? Surprise!) How does the Pharmacoepidemiologist know that? Good question. But if itâ€™s true, some heads are probably rolling in Whitehouse Station this week.
Speaking of whichâ€¦Peter Kim says he remains confident in Cordaptive and its dataâ€”no surprise there. â€œWe plan to meet with the FDA and to submit additional information to enable the agency to further evaluate the benefit/risk profile of MK-0524A [Cordaptive],â€ said Kim. But the consensus on Tuesday was that heâ€™s whistling in the dark. â€œNot approvableâ€ means, at best, another clinical trial lasting three years or more.
Is it worth the investment?
On the one hand, Merck was hoping to net $2 billion from Cordaptive alone, and also to spin off a Cordaptive/Zocor combo, as well as who knows what additional niacin-based packages.
On the other hand, FDA will be judging a whole range of up-and-coming anti-cholesterol drugs, from boring old statin combos to wild and crazy gene silencers. And Merck is currently just a lap behind Roche in the race to bring the first CETP inhibitor to market (or fail spectacularly like Pfizer). FDAâ€™s safety bar for that class is certain to reach new heights, but if the drugmakers succeed, the high-dose niacin approach to raising good cholesterol may take a back seat.
On a third hand, some observers detect signs that FDA is getting fed up with pharmaâ€™s obsession with anti-cholesterol drugsâ€”and by requiring new chemicals to meet higher safety srtandards is not only covering its own ass but deflecting R&D toward more innovative approaches.
â€œThe decision also comes at a time when the very idea of cholesterol-lowering is under increasing scientific attack. Yes, doctors know that the statin class of cholesterol-lowering drugs, like Lipitor, do prevent heart disease and heart attacks. But there’s growing evidence that a big chunk of the benefits of statins comes from reducing inflammation,â€ writes John Carey.
But for now Merckâ€™s entire cholesterol franchise is in free fall, along with its stockâ€”down 31 percent since January. As Avery Johnson reports in a withering Wall Street Journal piece, â€œThe setback raises doubts about the ability of Merck’s scientistsâ€”whose recent successes include cervical-cancer vaccine Gardasil and diabetes medicine Januviaâ€”to maintain the company’s competitive edge.â€
Thatâ€™s sure to wake up any Merck board members who slept through the past four months of bad press about their company (keywords: Vytorin, Enhance trial, Richard Clark).