Wednesday, August 15, 2007


The FDA’s philosophy seems to be that the way to protect the public from uncertainty about the safety of new drugs is to stop approving any at all. But who will protect the public from the FDA -- Henry I Miller, M.D.

These past several months, the Food and Drug Administration has been under severe attack by former officials, by unfairly treated pharmaceutical companies, and by patients in pain. Let us list a sampling.

Avastin, a breast-cancer drug, is delayed a year or more because FDA wants additional data. Moving the goalpost in the middle of the game is vexing for drug-developers, says Henry I. Miller, M.D., FDA official 1979-94.

The FDA some times requires testing long after it has approved the therapy. FDA approved doxepin for depression in 1969. Doxepin may be useful as a sleeping pill at very low dosage. FDA has ordered animal testing, a procedure always done prior to use on humans.

Vioxx, an arthritis drug for pain was withdrawn by Merck, its maker, when it was found to double the risk of heart attacks.(In the interest of full disclosure, two or three years ago, one snowy December night, a member of our household shook from every limb till Vioxx was administered. In 15 minutes, there was complete relief—a miracle!)

Arcoxia, a new arthritis painkiller from Merck, was disapproved by FDA. Its Director of the Office of Drug Evaluation ruled that “simply having another drug on the market” was not a reason “to approve the product unless there was a unique role defined.” FDA’s criteria for approval are safe and efficacious, to which the Director has added competition.

Why not let the patients choose which therapy is best for them? A drug that cannot be tolerated by one person, works wonders with another, says law professor Richard A. Epstein, author of a book on FDA. There’s no right answer. Arcoxia had already been tested on over 34,000 patients.

Genasense, a new drug, is for melanoma and chronic lymphocytic leukemia, CLL, which often appear together at a patient’s terminal stage. FDA denies to terminally ill patients their last resort, investigational drugs. It doesn’t want those near death to take any avoidable risk. FDA should have to show that its duty to society supersedes an individual’s right to be free from government interference.

Genasense caused complete disappearance of the disease in 17% of the patients in contrast to 7% in the control group. FDA disqualified the only sitting CLL expert on its Advisory Committee and added several non-experts to the Committee. Following the presentation designed to elicit a negative outcome, the Committee voted No by 7 to 3.

The company found a mathematical error in FDA’s analysis and has won the first round in court.

Bureaucratic revenge awaits challengers. FDA charged that TMJ Implants failed to do the paperwork indicating adverse events. TMJ denied it and appealed and waited for the case to come up. It waited. And waited. Finally FDA said, too late. We have just fined you $63,000. Your appeal would have been rejected since it is on the same issue as the fine.

TMJ is a small, one-product company. It has been in business a long time. It makes jaw-replacement devices. A big company would settle, but this small company could not afford it. FDA’s Center for Devices has lost its last four consecutive cases.

On May 9, 2007, “the dawn of a new era in cancer immuno-therapy was driven back into the night,” wrote Mark Thornton, former FDA official, as two new promising therapies were turned down by FDA. The first therapy, Provenge, is a cellular therapy that tackles prostate cancer in men for whom all other therapies failed. The search for this type therapy has been alive for a hundred years.

The second therapy, Junovan, was tested on children with osteosarcoma, a rare bone cancer affecting only 900 children a year. The presentation was to an FDA Advisory Committee of oncologists with no experts on immunology present. The results of both therapies showed that patients lived longer compared to control groups.

Provenge was approved by 13-4, but the minority four were influential oncologists who launched a PR campaign accusing the majority of incompetence. A few weeks after the Provenge vote, Junovan, by a different manufacturer, came before the Advisory Committee. It was turned down because the odds were 94% surety instead of the usual goal of 95%. The vote was No by 12-2. The meeting was chaired by the same influential oncologist who had launched the PR campaign against Provenge. Not one comment was made about immunology science’s supporting the efficacy of Junovan. Under the pressure, the FDA fell apart and declared it would not approve Provenge either, calling for more testing (three more years).

Viracept, for H.I.V., has been recalled by its maker, Roche Pharmaceuticals of Switzerland. Roche found an impurity, ethyl mesylate, which developed in the manufacturing process. The New York Times attacked Roche for discriminating against the poor, headlining its story “Roche’s Recall of AIDS Drug Hits World’s Poorest Patients.”

Richard Epstein pinpoints FDA’s basic problem:

Transfixed on the harms drugs can cause, the FDA remains largely oblivious to the harms they can prevent. Any delay in the use of a successful drug is costly: The delay matters little to the FDA, but a great deal to the thousands who plea for compassionate exemptions to try a drug that has not met with FDA approval.

By Natalie Sirkin
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