The plight of many MSers is witnessed daily by many in the medical community. These are just a few comments on their observations and thoughts.

3-5-06

For the record,

My wife Janet Dressell has been afflicted with Multiple Sclerosis since 1996 and we have followed the developments with various MS drugs; including Tysabri; quite closely over the past few years.;

I am writing to call to your attention that the testimony from John Richart; MD; representing the National MS Society; in the event he fails to call for the immediate re-approval of Tysabri with appropriate labeling and a risk management plan. He does not by any means represent the membership of the NMSS or others who are afflicted with this terrible disease. It is important to point out that there is a component of the NMSS that is dedicated to research that is funded in part by grants from several drug companies that wish to prevent or delay Tysabri from returning to the commercial market for blatant financial reasons. This has even been publicly disclosed in newspaper articles. Therefore; the testimony from Dr. Richart or others stating that they are representing the NMSS may be prejudiced for financial reasons and should be taken as such. The many MS patients testifying who have traveled from all over the country without any financial benefit are aware of the potential side effects of Tysabri; and they are the best representatives of the MS community which will be most affected by Tysabri’s re-approval. Please take this into account when weighing the testimonies.;

Respectfully submitted;

Terry L. Dressell DMD

3-2-06

WSJ EDITORIAL

Paternalism Costs Lives

By HENRY I. MILLER

March 2, 2006; Page A14

Decisions about drug safety and efficacy are far from easy. Tysabri, a multiple sclerosis (MS) drug that was voluntarily withdrawn from the market last year after the appearance of a previously unknown side effect, illustrates some of the conundrums.

In advance of the publication of three critical new studies on Tysabri in this week's issue of the New England Journal of Medicine, a major news organization recently asked me, as a physician and former FDA official, whether I knew of examples of prescription drugs that have "efficacy but [also] serious safety issues." That is, I responded, the rule rather than the exception.

Obvious examples include the antimetabolites used for traditional chemotherapy. Because these drugs are no more than poisons administered in a way intended to be more toxic to cancer cells than normal ones, it is not surprising that their side effects are often serious and even life-threatening. When I was a medical resident three decades ago, hospital gallows humor included referring to BCNU, an experimental cancer drug, as "Be seein' you." Approved in 1977, it is still widely used.

A more recent example is aldesleukin, a drug that has offered new hope to victims of kidney cancer and malignant melanoma. It is highly effective in a small proportion of patients but exhibits significant toxicity. The patient information booklet warns that those taking the drug "frequently experience serious, life-threatening or fatal adverse events," including dangerously low blood pressure and reduced organ perfusion, impaired function of infection-fighting white blood cells, disseminated infection and autoimmune disease.

Antibiotics are another class of wonder drugs that sometimes manifest significant toxicity. Chloramphenicol, a drug that is effective against a wide spectrum of bacterial infections, causes rare cases of fatal aplastic anemia, so it is used only sparingly. The potent antibiotic gentamicin is often lifesaving but can cause damage to the kidneys, nerves and ears. And significant numbers of patients are allergic to other important antibiotics, including the penicillins and cephalosporins.

But let us return to Tysabri, only the sixth medication approved -- and the first in several years -- for the treatment of MS, a common and debilitating autoimmune disease that affects the central nervous system. The impressive results of the drug's testing in clinical trials -- the frequency of clinical relapses reduced by more than half -- induced the FDA to grant accelerated approval in 2004. By the time that several thousand patients were being treated with Tysabri, however, three had contracted progressive multifocal leukoencephalopathy (PML), a rare neurological disorder caused by a virus. (Because the drug suppresses certain components of the immune response, regulators, clinicians and the product's developers had from the beginning been sensitive to the possibility of infections as a side effect.) Immediately -- some would say prematurely -- the manufacturers of the drug voluntarily halted production and distribution and withdrew Tysabri from the market. MS patients and many neurologists were bitterly disappointed.

The three clinical studies reported this week in the New England Journal of Medicine bolster our confidence about the safety and efficacy of Tysabri. In a study of almost a thousand patients that compared Tysabri to placebo, the drug cut the rate of clinical relapses by 68% (to 0.24 from 0.75), reduced by 83% the number of new or expanding brain lesions found on MRI, and slowed the clinical progression of disease. (The other currently used drugs for MS lower the occurrence of acute relapses by roughly one-third.) Similar results were obtained in a second trial which compared two-drug therapy with Tysabri plus interferon beta-1a to the interferon alone.

Finally, a third study found no additional cases of PML in more than 3,000 patients (exposed to an average of 17.9 monthly doses) who had participated in clinical trials of Tysabri. The investigators concluded that the incidence of this serious side effect is approximately one in a thousand patients treated with the drug. However, it should be noted that all three of the original cases of PML occurred in patients treated with interferon beta or other immunosuppressive agents in addition to Tysabri, so the risk might be significantly lower in patients treated with Tysabri alone.

The "safety" of a drug is a relative thing. Safety and efficacy, the two criteria required for marketing approval of a drug, are inextricably linked. The judgments of regulators (and practicing physicians) require a global and often difficult calculation of risk and benefit, including consideration of what alternative therapies are available. For a given drug, we are willing to tolerate greater uncertainty and more severe side effects for a potential cure for pancreatic cancer or AIDS, for example, than for a new drug that treats heartburn. When FDA grants marketing approval, the drug is deemed to be sufficiently safe and effective to be used for the conditions on the label.

In light of the just-published data -- to which the FDA should have had access months ago -- it is clear that this drug belongs back on the market, probably with new warnings about PML in the labeling.

The notion that the FDA should "err on the side of safety" sounds like a tautology but is an affront to patients with incurable or poorly treatable diseases: For them, there is no safety in the status quo, and we only damage them further with paternalistic public policy that prevents individuals from exercising their own judgment about risks and benefits. If the FDA must err, it should be on the side of patients' freedom to choose.

Mr. Miller, a physician and fellow at the Hoover Institution, headed the FDA's Office of Biotechnology from 1989 to 1993.

2-26-06

The FDA will not make a more important decision this year than whether or how to allow patients with MS to have Tysabri. Already the sceptics and critics are stoking the fires of doubt and negativism. Most prominent are those physicians and researchers who say [things such as] “Tysabri should not be allowed back because it is not a ‘cure,’ that is, it does not stop the progression of the disease, it does not target the true mechanism of neurological degradation, etc., and that since we do not know the long term side effects of the medicine the risk benefit profile of Tysabri is overwhelmingly negative.”

This standard, that the only drugs that should be approved are cures with no long term side effects, is nearly an impossible one to meet. Indeed, under such a standard, most -- if not all -- drugs for orphan diseases, cancer, HIV, MS and other degenerative illnesses would not be available to patients today. The constituency of rejectionism is convenient and easy to assume. It generates great press and attracts a lazy media that reports its position without challenge. A cure would be great. But note that the "cure uber alles" faction was formed in the United Kingdom where denial of new MS and cancer medicines is part of a larger effort to ration care and clamp down on costs even at the expense of quality of life and life itself. The author of a commentary in the British Medical Journal criticizing Tysabri as an "Uncure" was simply building the case for denying Brits access to the drug if and when the FDA approves it in America.

Such analysis fails to take into account the long term impact of disease and suffering of patients who suffer relapses from MS or the loss of independence, productivity and function absent access to medicines currently available or in development. And it fails to take into account that access to new drugs have been shown to reduce death and morbidity consistently over the past 40 years.

Finally, as we enter an era of personalized and targeted medicine, an era in which the response and reaction to drugs is a function of genetic variation and unique disease pathways, the decision about whether or not to have access to a drug should not be made by an agency or an advisory committee or second guessers in medical journals. It must and should be made by individuals and physicians after review of personalized information that provides a predictive picture of the risks and benefits of using a medicine. To the extent that genetic tests, previous clinical data, including a carefully kept registry of patient, and other diagnostics offer a predictive and personalized model of benefit, the decision to use a medicine should be left to the patient and physician. Nowhere is this model of medical practice more fully articulated, apart from HIV and cancer, than in the use of Tysabri. MS patients should push hard to make this personalized case. There should be no double standard in this regard.

There are lines of a a poem from Spoon River Anthology I often think of in times of transformation such as this:

And now I know that we must lift the sail
And catch the winds of destiny
Wherever they drive the boat.

Now is the time for MS patients everywhere to lift the sails of self-determination, to shape their destiny and drive their boats to greater freedom and better health. Show the world, the naysayers, the critics that you won't take no for an answer.

Robert Goldberg, Ph.D.
Director, Center for Medical Progress
Manhattan Institute for Policy Research

2-22-06

Letter to C-Span


Dear Sir or Madam:

As a neurologist who happens to also have multiple sclerosis and is active in patient educational seminars, I would like to request that C-SPAN cover the upcoming FDA hearings on a medication called “Tysabri” scheduled for March 7 & 8, 2006. As you may know, this drug was approved for the treatment of multiple sclerosis following very good efficacy data and then, just a few months later, withdrawn in February 2005 because of deaths from a severe brain disease that occurred as a complication in at least 2 MS patients in the trials (and a third case was discovered in another trial of the drug for another disease). The hearings will concern the potential re-introduction of the drug, as well as the kinds of restrictions the FDA may place on its use.

These hearings are very important for MS patients and their families; and given the recent turmoil surrounding FDA decisions in general, I think a strong argument can be made that these hearings are very newsworthy and of genuine interest not only for the MS community, but for the general public that needs to see how the FDA makes difficult decisions!

Please give your consideration to this important matter.

Sincerely,

Karl x. xxxxx, MD