Friday, September 15, 2006

Tysabri Follow-up

Several people have asked questions regarding TYSABRI, its recent re-introduction after the 2005 withdrawal as a result of reports of deaths of a few MS patients from progressive multifocal leukoencephalopathy (PML), a rare and frequently fatal, demyelinating disease of the central nervous system. As reported, these deaths occured in MS patients that were also taking Avonex.

As many people that know me are aware, I raised serious questions regarding the FDA approval of TYSABRI in the first place, given its then very brief clinical trials data. Over the past two decades, the FDA has taken greater and greater risks with health by a) accelerating the approval of drugs with increasingly less clinical trials data, and b) accepting increasingly lower threshholds for drug effectiveness prior to market release. While I agree that patients with many illnesses should have broader open opportunity to make decisions about new therapies, particularly when they are dealing with truly life-threatening diseases, too often in recent years, the pharmaceutical industry-influenced FDA has approved drugs that often show limited incremental benefit over drugs that are already on the market. In my opinion, this raises serious questions.

However, as long as the FDA is willing to pursue such strategies, it is in the hand of patients and physicians whether or not to try these newer drug therapies.

Based on the clinical trials data that were used for FDA approval, Biogen and Elan claim that TYSABRI "two-year data from the AFFIRM monotherapy trial showed that treatment with TYSABRI reduced the risk of disability progression by 42% (p is less than 0.001), the primary endpoint of the study, and led to a 67% reduction (p is less than 0.001) in the annualized relapse rate compared to placebo. TYSABRI treatment also resulted in sustained and statistically significant reductions in brain lesion activity as measured by MRI.

While the number of incidences of PML were low, and none were reported with TYSABRI therapy alone, I feel that it is only prudent that given the availability of competing immunosupressant or immunomodulating therapies for multiple sclerosis, that people weigh two important criteria:

1. The effectiveness of the alternative drugs;
2. Their own experience and tolerance of those drugs.

It is true, based on the data, that TYSABRI appears to be more effect than the alternative "CRAB" drugs in reducing relapse rates and the number of enhanced brain lesions.

While TYSABRI has shown to reduce the risk of disability progression by 42% as compared to placebo, AVONEX data shows a reduction of 37%; BETASERON data shows a reduction of 29%; COPAXONE data shows a reduction of 50%; REBIF (PRISMS STUDY) data shows a reduction of 30%.

While TYSABRI has shown to reduce the relapse rate by 66% (AFFIRM STUDY) as compared to placebo, AVONEX data shows a reduction of 44%; BETASERON data shows a reduction of 73%; COPAXONE data shows a reduction of 32%; REBIF data (PRISMS STUDY) shows a reduction of 32%.

Now here's food for thought: Keep in mind that there are several clinical studies that measure these important metrics. Some show better results than others, so it is difficult to offer truly direct comparisons. Additionally, keep in mind that while many of these data results are impressive, not every patient that takes on of these drugs actually receives all or any of the benefit. That's the dirty little secret that the pharmaceutical companies and many neurologists do not adequately disclose. In fact, of those that have participated in various of the clinical trials, in some cases as few as 35% of those taking a particular agent actually received benefit.

And then there are the statin drugs. While they have only been in small, early stage clinical trials - mainly because their manufacturers simply do not see the benefit of investing tens of millions or more in complete clinical trials when they are generating billions of dollars of revenues with these somewhat benign oral drugs in the anti-cholesterol market - there is modest evidence that statins may be of important benefit in at least reducing the number of brain lesions. More trials need to be conducted to gauge their effectiveness in reducing relapse rate and disability progression.

The conclusion of this piece is not that MSers should shy away from TYSABRI or any other therapy. Rather, be fully educated about the relative risks and benefits, the financial and side effects costs, and seek the guidance of a neurologist that specializes in multiple sclerosis.