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VIOXX: Systemic Problems Doom Another Systemic Drug BY ROBIN R. YOUNG CFA, OCTOBER 4, 2004

Since its introduction, more than 91 million prescriptions for VIOXX have been written in the United States for patients with arthritis pain in either the hip or knee. If one were to include all the prescription Cox-2 inhibitor drugs like Celebrex, naproxen and Naprosyn, fully 12% of adults in the United States (about 25 million people) reported taking prescription drugs for arthritis, according to a July 2000 Kaiser poll. In terms of its importance in the arthritis continuum of care, VIOXX took up one big piece of real estate.

Last week, with the writing clearly on the wall, the manufacturer of VIOXX, Merck voluntarily withdrew the nearly $3 billion dollar drug from the market.

There were systemic problems with VIOXX. Taken orally, the drug worked its way through the major organs, the brain, the heart, the gastro-intestinal tract before finally reaching the hip, knee and facet joints. While patients took VIOXX to treat arthritis pain, what they got was a full body treatment. We now know that that treatment included seriously elevated risk of heart disease and stroke.

Because of the way the drug was administered, namely through the entire blood stream, VIOXX had to be tested in 68 different studies involving almost 10,000 patients for an estimated cost of over $100 million before the FDA would review Merck's IND application in late 1998. Based on all those studies, the conclusion of the best minds both inside and outside the FDA was that VIOXX was safe to be prescribed.

Cox-2 inhibitors are a member of a class of drugs known as non-steroidal, anti-inflammatory drugs. Other examples of this class include ibuprofen, naproxen, Naprosyn and aspirin. All of these compounds work by inhibiting the cyclo-oxygenase enzyme (Cox-2) as well as inhibiting production of prostaglandin and prostacylin, the key source of inflammation in the joints. But, as most of us know, these compounds can cause gastro-intestinal distress. VIOXX had less of this than aspirin.

But, the drug was still subject to a final line of defense, the prescribing physician. VIOXX came with FDA approved warning labels and the prescribing physician was expected to withhold it from the patient if it was not safe for that person. And, we are now hearing a growing number did.

The human body is indescribably and unpredictably complex. Literally every attempt to intrude or introduce a new compound has a biologic consequence apart from the intended therapeutic effect; stents created restenosis and spine fusion created adjacent level disease.

Ironically, VIOXX was promoted to address one of the unintended consequences of the other Cox-2 inhibitors, stomach problems including but not limited to bleeding ulcers.

The single most promising solution to the fundamental problem of any drug that is administered either orally or via the blood stream, namely its systemic effects, is site specific drug delivery. This is particularly important for device manufacturers since their products can become (via biomaterial coatings or infusions of compounds) drug delivery vehicles.

Consider three cases; two in orthopedics and one in cardiovascular:

  • Infuse
    • Site specific drug
    • Accelerates healing
    • 2004 estimated sales: $250 million
    • Market value: $1.4 billion
    • Years on the market: 2.5
  • Synovial Fluid Substitutes
    • Site specific therapeutic (Drug? No, biologic, but therapeutically, same outcome)
    • 2004 estimated sales: $150 million
    • Market value: $550 million
    • Years on the market: 6
  • Drug Coated Stents
    • Site specific drug
    • Prevents restenosis
    • 2004 estimated sales: $2 billion
    • Market value: $10 billion
    • Years on the market: 4

Several of the companies presenting at this coming Biomaterials Summit have site specific drug delivery strategies. The date is October 15th. The site is the Omni Hotel, New York City. The registration web site is Be sure to attend and learn more about how different implantable materials can become drug delivery vehicles. It is only the future of medicine.

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