FDA to New Drugs: It's Hammer Time

Wonder no further whether the recent litany of drug-safety problems would make the Food and Drug Administration more cautious about approving new drugs. In just the past four days, the agency has thrown some serious sand into the industry’s drug-development works, delaying or derailing three separate programs of widely varying merit.

Consider:

• Earlier today, the FDA told Merck that its newish cholesterol-lowering drug Cordaptive was “not approvable,” and said the name wouldn’t pass regulatory muster either. Cordaptive is a combination of niacin (a form of vitamin B3 known to lower LDL, or “bad” cholesterol, while raising HDL, or “good” cholesterol) and laropiprant, a new compound designed to prevent the hot flashes and uncontrollable blushing people often experience when taking niacin. Per its usual procedure, the FDA isn’t offering the reasons behind its decision, and neither is Merck; instead, the drugmaker says it plans to submit additional data to the agency. This is quite likely bravado on the drugmaker’s part, as “not approvable” decisions tend to be very difficult to reverse. Still, if Merck was planning on distancing itself from its partner Schering-Plough in the wake of their mutual Vytorin scandal, this development was not at all helpful.
• Merck also got whacked by the agency last Friday when the FDA rejected its request to sell a combination allergy pill consisting of its drug Singulair and Schering-Plough’s now-generic treatment Claritin. Again, both the FDA and the companies have been mum, although according to the In Vivo Blog, Merck says the FDA didn’t raise any “safety or tolerability issues.” That leaves the door wide open as to what issues FDA did find with the combo pill.
• Also last Friday, the FDA told Genzyme and Isis Pharmaceuticals to submit additional data for their experimental cholesterol-lowering drug mipomersen. The decision amounted to a one-two punch: The companies must complete cancer studies in animals before requesting approval of mipomersen as a treatment for a rare high-cholesterol genetic disease, and then have to prove that mipomersen can reduce the risk of heart attacks or similar diseases before marketing it more broadly.

Of course, not all new drugs are created equal, and in at least two of these cases, you can make a pretty good argument that neither proposed drug is that much of a loss. Nothing currently prevents anyone with a Singulair prescription from also taking Claritin if they want to, for instance, so the need for a combination drug doesn’t seem particularly pressing. Similarly, the actual benefits of Cordaptive — or whatever Merck ends up calling it, assuming it survives — appear to be pretty small, particularly once you consider the fact that laropiprant hasn’t been extensively studied and may have side effects of its own.

The Genzyme/Isis drug, by contrast, represents an entirely new way of lowering cholesterol by “silencing” the genes responsible for producing and shuttling LDL around the body. The problem these days is that finding innovative ways to lower bad cholesterol isn’t enough, thanks to — you guessed it — a recent large study of Merck and Schering’s drug Vytorin, which lowered cholesterol but failed to show any signs of reducing heart-attack danger.

None of these actions are surprising in and of themselves, and even taken together they don’t reveal much more than the fact that the FDA does react to public concerns about drug efficacy (think Vytorin and the shenanigans Merck and Schering pulled in an apparent attempt to bury those findings) and safety (think GlaxoSmithKline’s diabetes drug Avandia or Merck’s Vioxx).

Pretty much everyone in the industry knows that the FDA’s concerns about drug safety ebb and flow depending on what sort of drug problems seem to be dominating the headlines. The agency, however, can’t ever bring itself to admit that, even though it’s very clearly a political football these days. And the result of its failure to set clearer safety standards and stick to them over time, instead of reacting episodically to crises, creates real problems for the industry and the public. Companies and their investors never know exactly where they stand with FDA, which in turn fuels criticism that the agency is capricious (which it sometimes is) or that it’s unfairly impeding innovation (which it usually isn’t).

A big part of the problem is FDA’s insistence that the companies submit to the agency must be considered proprietary information. That’s what’s behind the agency’s silence in its recent drug rejections, and it’s one of the single biggest obstacles to restoring a proper balance between approving badly needed new medicines and drawing the line against those whose benefits or risks haven’t been fully studied.

Look no further than the emerging scandal involving experimental blood substitutes, which appear to increase the risk of death by 30 percent and triple the danger of heart attacks. Researchers say the FDA should have known about the safety issues eight years ago, although the agency instead approved further trials without sharing the data it already had in its possession. For another, consider a case in which Glaxo apparently cherry-picked data from a study of its antidepressant Paxil to show the drug was safe and effective for teenagers, when in fact a full analysis of the data linked it to serious nervous-system disorders and other side effects.

The FDA has a tough enough job on its hands without a self-imposed gag order that shields its regulatory decisions from scrutiny and informed analysis. Cloaking its activities in proprietary obscurity doesn’t do the agency — much less public safety — any favors.

Image by Flickr user PPDIGITAL, CC 2.0