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Vioxx, an arthritis drug for pain was withdrawn by Merck, its maker, when it was found to double the risk of heart attacks.(In the interest of full disclosure, two or three years ago, one snowy December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


Anonymous said...

Great article! Cancer patients and advocates will be holding an FDA rally September 18th to raise awareness of the current situation and elicit change at the FDA in order that cancer patients may gain access to promising therapies not yet granted FDA marketing approval. You can find out more at: Please come support cancer patients September 18th. Every voice counts.

Tony F said...

GREAT article about the goings-on at the FDA and how it adversely affects cancer victims! Thanks!

Regarding Dendreon's PROVENGE, a compilation of Conflict of Interest (COI) for Scher of Sloan-Kettering who sat on the Provenge March 29 FDA Advisory Committee and who voted “YES” that Provenge was substantially safe and “NO” that is showed substantial efficacy indicatges he has UNdisclosed COI's.

Sources are public information available on the internet.

Scher reported only 3 COI’s to the FDA in his Waiver Application permitting him to sit in judgment of Provenge which appears to be composed of ownership of 1 stocks and 2 competing industry interest.

Internet research shows the following for Scher thus far:

1. NOVACEA: grants & research support; STUDY CHAIR of DN-101; Direct competitor to Provenge

2. GPB BIOTECH: financial conflict of interest per Scher in MedPage

3. PHARMION: financial conflict of interest per Scher in MedPage

4. SANOFI-AVENTIS: grants & research support

5. BRISTOL MYERS SQUIBB: consultant, grants & research

6. MILLENNIUM PHARMCEUTICALS: grant of research support

7. COUGAR BIOTECHNOLOGY: principal investigator; advisory board;

8. INNOVIVE PHARMACEUTICALS: principal investigator

9. INFINITY PHARMACEUTICALS: principal investigator

10. BIOGEN-IDEC: jointly held stock with spouse

11. PFIZER: jointly held stock with spouse

12. GENTA: scientific advisory board (as of March 6, 2007; since
removed from web, but cached)

13. DEPARTMENT of DEFENSE: Principal Investigator PC Clinical Trials-P1 and P2

14. MEDIVATION, INC: principal investigator MDV3100

15. AMBRILIA BIOPHARMA INC: Principal Investigator PCK3145, Phase I/II

16. PROQUEST INVESTMENTS: consultant, scientific advisory board; LIMITED PARTNER FINANCIAL interest

There appears to be a significant and disturbing difference between his 3 disclosures to the FDA and the alleged 16 COI’s found so far on the internet. It seems incomprehensible for someone with the training and education Scher has to “forget” so many apparent COIs… that is simply beyond all reasonableness and suggests intentional dishonesty or deceit.

Even more disturbing is the FDA’s Office of Inspector General and others at the FDA to whom this information has been supplied and their apparent failure to investigate these charges that Scher has more COI’s than he disclosed to them. When such information is provided and such allegations of potential federal law violation is involved, any ordinary citizen has the right to expect our government to investigate such allegations timely and thoroughly.

As a “temporary government employee” at the FDA, he is obligated, under Federal law, to provide full and complete disclosure. If he didn’t, he may have the potential for liability for law violation(s) as well as for providing false data to the FDA under which he secured a waiver in order to participate on the Provenge AC meeting March 29th.

Advocates, cancer patients, family and others will Rally at the FDA in Washington on Sept 18. Details are at Support cancer victims according to your ability… come to the Rally, join caretolive, volunteer to drive or sit with a cancer victim… however, you can. If we don’t help them, who will?

Hopefully, this information will peek the interest of someone in the media to investigate whether or not these allegations are true or not and expose this tragedy which allows 83 men to DIE each day from prostate cancer.

Thank You! For you article bringing the FDA’s action to the public view.

kevin said...

I appreciate your article pointing out that the FDA has become risk averse, thinking that by doing nothing they will never make a mistake.

Yes they have suffered some bad pub because of some decisions made earlier, but especially when it comes to terminal patients, some intellectual flexibility should be exhibited. Slavish adherence to statistical models serves only the bereaucracy, giving it a legal leg to stand on in court.

Anonymous said...

It is conflict of interest in the FDA that keeps these drugs off the market. When you research the monies these doctors are paid by big pharma, it is appaling that they have the power to keep rival and potentially better therapies off the market. It is the usual story, money and power corrupts and the patients are left to die.j

Mara said...

Excellent article....covers a lot of ground. A "must read" for those who are desperately waiting for the FDA to act in a responsible and timely manner to grant approval to effective and safe drugs and/or therapies.

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