Posted on 04/29/2005 4:57:26 AM PDT by Paul_B
Drug withdrawal a travesty for MS sufferers
Michael Fumento (archive)
The yanking from the market of both Vioxx and Bextra, members of a new generation of pain relievers called COX-2 inhibitors, has critics ripping raw flesh off the Food and Drug Administration. Inevitably, both the agency and pharmaceutical companies are under intense pressure to over-scrutinize new drugs. But over-caution can also cause tremendous, as multiple sclerosis sufferers using a recently-pulled drug called Tysabri can attest.
Tysabri belongs to an incredibly promising new class of biotech drugs called monoclonal antibodies. Monoclonals have repeatedly shown an ability to slow or reverse diseases for which previously there had been nothing available but pain relievers and to be effective against multiple diseases.
Such appears to be the case with Tysabri, produced in partnership by Biogen Idec and Elan Pharmaceuticals and approved for MS in late November. About 400,000 people in this country have MS, in which the immune system attacks both the brain and spinal cord and causes a host of symptoms including blindness, paralysis, and sometimes death.
There are other MS drugs, but none seem nearly as effective as Tysabri or as well-tolerated. In fact, results released this month of two years of clinical trials showed a stunning a 42 percent reduction in the risk of disability progression and an even more amazing 67 percent drop in clinical relapses.
In late clinical trials Tysabri has also apparently been extremely effective against Crohns disease, a severe bowel disorder. Additionally, it was also in human testing for rheumatoid arthritis. So it came as a stunning blow to the approximately 8,000 patients using the drug, as well as a long list of persons waiting to get prescriptions, when the axe fell.
The force behind that axe was a tiny virus thats extremely common but that the immune system keeps locked up. If unleashed, though, it causes an often fatal disease of the central nervous system called progressive multifocal leukoencephalopathy. Unfortunately two MS patients on Tysabri contracted the disease and one died. When the drug makers scoured their databases they found another PML death in a Crohns patient. He also died.
Its possible that in suppressing the immune systems attack, Tysabri may have let loose the virus. But tremendously complicating matters is that all three patients were also on other immunosuppressive drugs at the time, leaving the real possibility that Tysabri alone is harmless. There are NO known cases of PML in patients using only Tysabri, according to the FDA.
Whats bizarre to Dr. Jeffrey Horstmyer, director of the MS Center at Mercy Hospital in Miami, is that less-effective MS drugs known to kill people have been used for years. We allow Novantrone, he says, and yet take Tysabri off the market. Novantrones side effects can include heart failure and leukemia.
Likewise all the drugs that slow the progression of rheumatoid arthritis carry FDA warning labels, and two have been implicated in several deaths. Yet sufferers practically worship the companies that make them.
Tysabri is a great drug, says Horstmyer. My patients . . . were delighted with the lack of side effects and its effectiveness. He adds theyre really ticked that its been pulled. In fact, New York Newsday headlined a recent story, MS Patients Plead for a Recalled Medication and the drug makers are being deluged with requests from desperate MS sufferers.
Horstmyer thinks the threat of lawsuits was primarily responsible for the drug being withdrawn, while the Competitive Enterprise Institutes Sam Kazman blames government. What weve apparently got is FDA reverting to its traditional operating mode of deadly over-caution, he says. That plays well in both Congress and the press but its murder on patients. Yet both agree that but for the COX-2 calamity there would have been no withdrawal and its wrong for Vioxxs tentacles to be reaching out and grabbing other drugs.
The Biogen and Elan people were trying to demonstrate the highest level of scrutiny in pulling Tysabri until all patients could be evaluated, says Horstmyer. But, All the MS drugs have serious side effects, he adds. Moreover, patients with MS are among the most well-informed, he says, and best able to balance the risks of their disease versus the rewards and risks of various drugs.
Says Horstmyer, I really hope they can bring Tysabri back.
Michael Fumento (mfumento[at]pobox.com) is author of BioEvolution: How Biotechnology is Changing Our World, a fellow at Hudson Institute, and a nationally syndicated columnist with Scripps Howard News Service.
©2005 Michael Fumento
This is the legal and political environment we have come to, where patients in need and honest investors are punished so that senators can grandstand and lawyers can become rich.
Hopefully, Tysabri will be back, soon. And hopefully we can finally get some tort reform. The current legal/political situation is quite literally killing us.
Who would have thought this could happen with the party of Reagan in charge?
(AP) In other news Senate Minority Leader Reid denounced the Bush regime for the Tysabri debacle, pointing to both the high death rate and the unannounced and precipitate ban as having an undue effect on minorities and women.
Here's the problem with Tysabri, IMHO.
The reason it was yanked is because PML symptoms are so similar to MS symptoms that it is impossible without an MRI, lumbar puncture, or brain biopsy to determine if the patient is just experiencing an MS exacerbation or is experiencing PML symptoms.
To make matters more complicated, the normal thing a neuro would do if he saw a MS patient with worsening symptoms would be to put them on a course of IV solumedrol (steroids) and if the cause of the worsening symptoms was PML, then that would make the PML become even more aggressive. (and since 80 percent of people harbor the JC virus which causes PML, it does not good to try to avoid people with the JC virus when administering Tysabri.)
Tysabri was shown to reduce exacerbations by 67 percent versus 33 percent for the other treatments, but the EDSS (disability scores)of Tysabri versus a placebo were no better than those patients treated with an interferon versus a placebo (about a 12 percent reduction). Most neuros will tell you lesion load has no impact on disability.
I can see Tysabri coming back as a Crohns or RA treatment sooner than as an MS treatment. And if it comes back as an MS treatment with a warning about immunosuppressants (i.e. steroids), I think there will be problems getting it accepted widely by the MS community.
Another issue with Tysabri is the cost, it is by far the most expensive of the present treatments because it has to include the cost of the infusion, when the other treatments are self injected.
There will be a market for Tysabri. Those who have side effects from the interferons, or have developed antibodies to them so that they are useless, or perhaps those with liver problems from the interferons. There are plenty of people who refuse to take a CRAB (copaxone, rebif, avonex or betaseron), but not all those people don't take them because the other treatments have failed. They just don't want to take that strong a medication, or use alternative therapies like LDN. Those that have refused to be on a CRAB for that reason, will also probably refuse Tysabri.
I do hope Tysabri comes back to the market, I just don't think it will have as wide a market appeal as there was before the PML was discovered.
The decision to pull T. has been devastating to so many. It does look, though, that it will be back in a few months, Lord willing.
How trial lawyers kill people and make them suffer in America for their profit...
Thank you very much for this informative explanation.
I see so many people getting caught in emotional half-arguments. I know investors are at a huge loss for now, are filled with hyperbole and are indiscriminately blaming all persons and organizations for their loss. MS patients and relatives of MS sufferers are also easily drawn to the side that views the cancellation of Tysabri as unnecessary.
I hope the companies involved in Tysabri are fortified enough to continue research and will find ways to manage problems with the JC virus.
Please post again if you have any insight into possible remedies for research. Thanks again.
Yes, PML signs are similar to those of MS, but no Lumbar punctures have been done in the detailed followup testing of the patients who have taken Tysabri. In fact, probably more is now being learned about PML and its differences from MS than ever.
Tysabri on monotherapy has a sterling record. The problem is quite evidently immunosuppressant synergies, which the label already warns against.
As this article brings out, the safety profile of other drugs in accepted use is far worse than anything associated with Tysabri. I believe the drug comes back with a warning label and becomes the standard of monotherapy in a short time. Neuros will undoubtedly demand waivers from patients, but patients will want the drug. From what I've read, the EDSS scores are not a particularly great way to guage actual quality of life.
You said:
"Tysabri on monotherapy has a sterling record. The problem is quite evidently immunosuppressant synergies, which the label already warns against"
I just don't know too many MS patients who are willing to write off steroids as their first line of attack during an exacerbation.
As far as the EDSS not being a way to gauge quality of life, it takes into account 8 different functional systems.
Most people think it only deals with mobility, but it does deal with other symptoms, or functional systems.
Here's a link to the expanded scale.
http://www.mult-sclerosis.org/expandeddisabilitystatusscale.html
We lost my mom's cousin to MS. (We did get a good 25 years with him.) I pray that the FDA comes to it's senses soon.
You wouldn't happen to know exactly what Tysabri targets, would you?
If you mean the action of Tysabri...it keeps T-cells from crossing the blood brain barrier. This helps the MS patient by limiting exacerbations, as t-cells are what cause destruction of the myelin.
But since the PML cases cropped up, it was wondered if the action of blocking t-cells from crossing the blood brain barrier was what caused the JC virus to go unchecked and the MS patients to come down with PML.
PML is usually only seen in severely immunesuppressed patients, such as AIDS patient.
The PML was found only in the MS patients who had taken Avonex and Tysabri, but since Avonex (an interferon and immune modulator) has been on the market for about 10 years without incidence of PML, the question arose as to whether it was the Tysabri that led to the PML.
Of course, steroids (immune suppresants) were thrown in the mix once the MS patients in the trial started having worsening symptoms, because the worsening symptoms were thought to be an MS exacerbation.
One MS trial patient died, the other, last I heard, had been moved from a hospital to a rehab and was making a slow recovery from the effects of the PML.
So the question that remain to be answered if Tysabri is reintroduced is: Why did PML develop when Tysabri was given to the MS patients? Did it have something to do with the combination of the Avonex and the Tysabri?
(There was a third patient who came down with PML and died, this patient was a Crohns patient, and was not on an interferon. However, this patient had been on other immunosuppressant drugs, in addition to the Tysabri.)
End government restraint of drug therapies. Abolish the FDA.
Do waivers hold up in court? Sounds like the best tort reform right there.
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