FDA's Approvable Problem - Pharmaceutical Executive


FDA's Approvable Problem

Pharmaceutical Executive

Analyst Steve Brozak, president of WBB Securities, agrees. "It's to the point where it's by exception—not the rule—that drugs are approved," he said, and then raised another red flag: "Innovation and safety are contraindicated. Pharma can't have blockbusters in very large populations at the same time FDA has no safety signals."

In a study released in August, James Kumpel, an analyst at Friedman, Billings, Ramsey, reported that FDA OK'd 38 new drugs between January and July, down 31 percent from 55 approvals for the same period in 2006. Meantime, the number of new molecular entities (NMEs) is at a 10-year low, seven through July, compared with an average of 12 over the same period every year since 1998. "They've raised the bar," said Kumpel, whose study helped spark a recent media flap about the drug-approval slowdown. "They've made it more difficult for drugs to get through the system."

Gretchen Dieck, Pfizer
It doesn't take a scientist or analyst, however, to detect that different drugs are being treated differently in FDA's decisions:

Big-market drugs Innovative drugs for common chronic conditions that will be used by millions of people are getting scrupulous scrutiny—particularly for heart and liver toxicity—and are routinely found wanting. The message seems clear: No more Vioxxs! As a result, pharma has had to sit on its hands as one after another potential top-seller gets jettisoned.

Me-too drugs These seem to be hit hardest of all. In 2005, only one of 14 me-too drugs won approval on the first try—another 10-year low. The poster child for these drugs is Merck's Vioxx spinoff, Arcoxia (etoricoxib), which didn't even earn an approvable letter. To many observers, FDA's new unofficial policy seems to be that me-too drugs don't just have to prove safety and efficacy—they have to prove superiority to existing drugs. "The discussion on what this [drug] brings over and above what's on the market is a question that's being asked," Vasella told the Financial Times. "FDA doesn't seem to trust the physicians any more."

Second indications Given that these drugs are already in wide use, their safety profile should present fewer uncertainties. But the agency asked to see more data for Wyeth's Pristiq (desvenlafaxine) and Endo's Frova (frovatriptan succinate), both for menopause; Encysive's Thelin (sitaxsentan), for hypertension; and Trexima (naproxen and sumatriptan), a new combination being codeveloped for migraine by Glaxo and little biotech Pozen, whose stock value dove by half at the news. The NASDAQ Biotechnology Index is down about 14 percent since last winter, a drop some analysts attribute to investor skittishness about the FDA's abundance of caution.

Priority NDAs FDA has seemed careful not to put the brakes on approvals for important drugs for life-threatening diseases; each gets not only a speedy six-month review but its own risk/benefit ratio. In oncology, for example, Pfizer's TKE inhibitor, Sutent, became the first drug ever approved for two indications at its first time at bat. First-in-class cancer drugs that sailed through include Wyeth's mTOR (mammalian target of rapamycin) inhibitor, Torisel, and Glaxo's first small-molecule ERB1/2 inhibitor, Tykerb. Yet with oncology pipelines exploding, the gate may be closing. According to Tuft's Chris Milne, the agency has delayed (or rejected) five promising cancer therapies since January, including Genetech's Avastin (bevacizumab) for its third indication, breast cancer. Another NDA was blocked on dubious grounds, Milne says: "FDA told the company it doubted the postmarketing studies were going to be done on time and demanded the firm do them before approval. But, in fact, 89 percent of postmarketing studies in oncology meet their deadlines." And since such studies can take five to 10 years, the drug was DOA.


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