Biogen, Tysabri & A Dying Democratic Fundraiser
32 CommentsBy Ed Silverman // October 15th, 2008 // 3:06 pm
Fred Baron, a prominent Dallas trial lawyer who helped bankroll John Edwards’ presidential run and also paid for the former senator’s mistress to leave Chapel Hill, North Carolina, after the affair made national headlines, is dying of multiple myeloma. But money won’t buy the wealthy, 61-year-old Democratic Party fundraiser a medication that may improve his odds of living beyond the next few days - Tysabri, which is sold by Biogen.
Despite a furious publicity campaign drummed up by his son, Andrew, Biogen refuses to make the medication available. Never mind that calls to Biogen ceo Jim Mullen were placed by various politicians - Bill and Hillary Clinton, Henry Waxman, Ted Kennedy, Tom Harkin, John Kerry - or their staffs. Oh yes, Lance Armstrong also rang. Mullen is resolute that Baron will not receive Tysabri.
Why? A Biogen spokeswoman tells us the drugmaker has a policy of not making Tysabri, which is approved only for treating multiple sclerosis and Crohn’s disease, available for any other treatment, even for compassionate use. That’s because the med was linked to a deadly brain infection - PML - which prompted a withdrawal in February 2005. Sales resumed in July 2006, but only under a closely controlled program that restricts access and usage.
The Biogen spokeswoman tells us that, given the drug’s complicated history, any inadvertent reactions Baron may experience could, theoretically, jeopardize its use for multiple sclerosis and Crohn’s patients if it would somehow cause labeling to change or spark another regulatory review. Biogen has similar concerns for the outcome of a Phase I clinical trial testing Tysabri for treating multiple myeloma. Two more cases of PML, for instance, were recently reported in Europe (read here).
“There’s no human data on whether tysabri may be effective for multiple myeloma,” she tells us. “We’re not going to do emergency use because of all these issues. We want to protect access for patients who are on drug now and rely on it. These decisions are never easy and we understand it impacts real families. But that said, we feel like we can’t make an exception in this case and risk further limiting access for the more than 32,000 patients with MS and Crohn’s who depend on the drug…And we don’t want to put at risk further clinical trials for multiple myeloma.”
On his blog, Andrew Baron writes that the FDA informed Biogen that making Tysabri available for compassionate use would be acceptable, and that the FDA would be willing to exclude any adverse reactions from what he described as “future considerations against the company,” a reference to its clinical trial. An FDA spokeswoman tells us that the agency is, in fact, agreeable to compassionate use, but we are still awaiting clarity on the point about consequences for Biogen’s clinical trial.
UPDATE On Thursday, October 16: An FDA spokesman writes us to say this: “The FDA is working with the company and the health care professionals involved - as we would with any such request - under the provisions of FDA’s expanded access program.
“Regarding your other question: Did FDA assure the company that if the drug were administered to Mr. Baron and it did not work, or caused harm, the agency would exclude this data from its future consideration of the drug?
“The FDA has provided no such assurance to the company. Our policy is to consider all available information when evaluating the safety and effectiveness of drugs. We recognize and appreciate that expanded access programs involve less-controlled use of experimental treatments than the well-controlled environment of a clinical trial, and thus we would consider information that might be obtained in this instance within that context.”
Anne
Shouldn’t that be John Edwards, not “Jim”?
Andy
I’m sure he wishes it was “Jim.”
Ed Silverman
John who? Just kidding. I goofed for some reason I can’t figure out, other than I know someone named Jim Edwards. Anyway, thanks for the heads up. But I guess John Edwards didn’t make much of an impression on me to begin with.
Cheers
ed
Steve
I sense more concern for what the FDA would say, along with the politics, than to give a dying man the drug. Talk about “compassionate use”! So much for the “compassion” part.
NyHack
Here we go again, pharma/biotech evil… everyone else not to blame. FDA sure seems covered here too.
This story is now creeping out of the blogdome and into more mainstream media with little context being provided.
Given that a trial is underway in Multiple Myeloma with Tysabri, do you think there is no potential harm in providing Mr Baron the drug? Despite the FDA approving compassionate use, I could easily see an situation where something goes wrong with Mr Baron and next thing you know, the MM trial is put in jeopardy. Not even to mention the thousands of patients with MS for which this drug presents a real option. The FDA is in a can’t lose situation by saying they would allow compassionate use here, Biogen is in a can’t win.
Marguerite
I could just as easily anticipate Mr. Baron’s treatment going well, leading to widespread positive press for Biogen.
Steve
Marguerite
Well said! The dying man has absolutely nothing to lose. Your Mojo is in full swing!
Anne PME
As someone who has first hand knowledge of compassionate use, I understand Mr. Baron’s desperation, and I wish him all the best. From the sound of things, he has a good medical team and a great support system in his battle against MM.
Compassionate use can sometimes involve reimportation. In these circumstances, the patient cannot be participating in a clinical trial, and any results are not part of clinical trial data, so it is surprising that Biogen is worried about PML in this specific case.
Paul
Compassionate use? It hardly ever is! Indeed,in most instances compassionate use is little more than a process for providing preferential access to someone with influence. Since Tysabri is marketed, under ordinary FDA policy, a licensed health practitioner would typically be free to prescribe Tysabri for an off label indication (e.g., cancer, psoriasis,hemmorhoids, etc.) if he deemed it to be in the best interests of his patient. That presumably won’t work here because Tyabri is not available in ordinary pharmacies, but is distributed to patients with MS and Crohn’s under a risk management plan operated on behalf of Biogen Idec. Nonetheless, it appears that Mr. Baron’s physician can get the FDA to open an IND for Tysabri’s investigational use in a single patient with Multiple Myeloma, but that still won’t work if Biogen Idec won’t agree to supply the drug. Personally, I don’t believe Biogen Idec has any moral obligation to supply its drug to Mr. Baron although I doubt there would be much risk to them or Mr. Baron if they did. From a drug development perspective, however, allowing ‘compassionate access’ for selected individuals while randomized trials are ongoing with a drug is not a good idea. When clinical trials are ongoing, as a matter of fairness, access should only be be granted to those willing to run the gauntlet of randomization.
Mike
There is appearance and there is reality.
Appearance: In 2005, Biogen pulled the drug Tysabri from the marketplace voluntarily when 2 PML cases were discovered shortly after its approval.
Reality: The FDA, which had been abused by the media and Congress for ignoring Vioxx safety problems the year before, put a gun to Biogen’s head in Feb 2005 and basically said pull this drug or else we will. The motivation for Biogen to agree was that the FDA left the door open for re-approval if they pulled the drug “voluntarily”.
Appearance: Biogen designed a risk-mitigation program which prohibits off-label usage.
Reality: Biogen “designed” a program that was basically dictated to them by the FDA. Even though Tysabri would be very interesting in a number of different auto-immune diseases, the FDA was determined to show its regulatory chops by restricting usage to multiple sclerosis. Therefore, the “voluntary” risk-mitigation program prohibits off-lable usage.
Appearance: Biogen would never be impacted by a negative clinical result if Fred Baron took Tysabri and died. Why? Because the FDA said so.
Reality: Even if Tysabri were to “cure” his cancer, Fred Baron is an immuno-compromised individual as a result of his prior cancer treatments who would be susceptible to PML. He has apparently taken Campath, which basically eliminates all of your B cells and severely compromises your immune system (which protects you from PML and other infections). If he were to contract PML after taking Tysabri, the FDA would naturally count this as a strike against the drug in the cancer setting. In addition, Tysabri usage in Multiple Sclerosis and Crohn’s would decline as patients over-react to a PML case which will be widely reported in the media due to Fred Baron’s fame.
It is unfortunate for Fred Baron, but it is the FDA — and the media — which has persecuted this drug for the past three years. The drug has risks, but the rewards far outweigh these risks in just about all cases. This drug never should have been pulled in the MS space and it never should have had these ridiculous “voluntary” restrictions which prohibit off-label usage. Let doctors practice medicine! Instead, we have the FDA covering its butt by letting ONE well-connected individual potentially have access to this drug, and setting Biogen up for a “lose-lose” situation.
Biogen is right to stand up to the FDA for putting it in this ridiculous position. If off-label usage is justified for Fred Baron, then it is justified for everyone with multiple myeloma and other conditions where Tysabri may be useful. (Every other drug in the universe which is approved for one indication may be used for other indications if the doctor believes appropriate.)
If Tysabri for multiple myeloma is only good for Fred Baron, then the FDA is not going by clinical or scientific principals, but merely reacting to political pressure.
ANDREW
they should find someone with Crohn’s disease and pay them for a months worth of of pills. i am sure Baron has enough money to spend few thousand per pill.
Former pharma Marketing Exec
This is completely unacceptable behavior on the part of Biogen.
The FDA which is the major ruling hurdle in this case have stated that they would allow access to this drug for this use.
The close mindedness of the people at Biogen should speak very loudly to their clear lack of vision.
They now are making a strong public case and willing to sacrifice another human beings access to a drug that may - MAY, provide him some assistance, and all to make a political point for being asked by the FDA to provide more data on the PML issue.
How the powers that be at Biogen can possibly link the two issues in the face of this current situation is beyond comprehension.
This isn’t about access for the elite either. This is about the true definition of compassionate use.
Shame on the administration at Biogen.
Providing this drug compassionately could very well produce some interesting data for Biogen and that the “would be patient” already knows the risks involved and is willing to take them anyway is an opportunity they should not be throwing away for the sake of political posturing.
Here we have someone who is fully informed, knows the risks involved and yet Biogen has found a way, in their minds anyway, to withhold access.
The argument that providing access to this drug while randomized trials are still underway is detrimental in some way, is an empty argument. The data from Mr. Baron’s use of the drug doesn’t affect the trial results because it is not part of the trial protocol. It becomes experiential data - that’s all!
Shame, shame, shame. Maybe they should stick to other disease categories than cancer, because they are clearly showing a complete lack of compassion and humanity. With “friends” like this, cancer patients need no further enemies..
NyHack
What about the rest of the patients in the Multiple Myeloma trial underway Former Pharma? What do you say to those individuals. There will be individuals randomized into an arm of the trial who will not receive Tysabri when they begin the Phase 2 portion of the study, how can you deny them this drug if you are willing to let a well connected individual receive Tysabri for the same condition outside of the trial?? Read the post by Mike above to get a sense for some of the things at play. Again Biogen is in a lose-lose situation.
This is being widely reported now by mainstream media and in many cases with absolutely no context, shameful.
Nathan
FPME writes: “This isn’t about access for the elite either.”
It’s not? Then where do they stop? If Fred Baron gets the drug, then what happens when the thousands of other multiple myeloma patents also line up to get the drug? Why should Fred get it and the others don’t? If start down the road of “compassionate use”, then where does it stop? Sooner or later, FDA approval becomes meaningless for terminal illnesses.
Steve
Nate
I wonder if you would make that same bold statement if God forbid, it was one of your beloved family members! If so, you are indeed a cold man.
I make this conclusion: You are just a level headed businesss man who doesn’t want to rock the boat.
By the way, “compassionate use” is part of the FDA operation, and, has been used many, many times.
PJ
A patient who is initially immune suppressed who would then go on Tysabri might be at very high risk for PML. I can see both sides of this issue.
Nathan
Steve, please answer a couple of the questions I pose and then we’ll have a discussion. I noticed only insults in your post — no answers.
Steve
Nate
What are your questions?
By the way, you may take these comments as “insults”. These are observations, certainly not to be invective.
Ram
Millennium Takeda’s Multiple Myeloma drug didn’t work? How about Celgene’s? why go for something in phase 1?
Nathan
Steve, I’ll repost my questions:
“If Fred Baron gets the drug, then what happens when the thousands of other multiple myeloma patients also line up to get the drug? Why should Fred get it and the others don’t? If start down the road of “compassionate use”, then where does it stop?”
Continuing with these questions, why should cancer drugs get FDA approval at all? If cancer patients can just get drug directly from the company without FDA approval, then why should they bother getting FDA approval at all? What is the incentive for anyone to join a clinical trial? If they want the drug, they can just get it from the company. No need to enroll in a clinical trial where you may or may not get the drug.
Opening up drugs for “compassionate use” sounds great — until you start thinking about the implications of it.
Anne PME
Compassionate use would not be widely available b/c insurance does not generally cover it. Unfortunately, most people cannot afford to pay for these types of medical treatments out of pocket.
If the patient tries to get authorization from the insurer under compassionate use, they could potentially by held financially responsible for the treatment and all related aspects of treatment- i.e. things like administration, scans, bloodwork etc. Read your insurance certificate- chances are that there is a waiver for experimental therapies. Insurance companies now often interpreting this to include off label use of FDA approved drugs. In some cases such as certain FDA approved cancer indications, reimbursement is limited to the specific type of cancer that the drug is FDA approved for.
Steve
Nate
First paragraph, good question but your thrust was a cold one. Maybe, should have toned it down.
“Where does it stop”? My ether answer, I don’t know. But the person who has exhausted every other avenue, this could be the one that worked.
“Why should cancer drugs get FDA approval at all?” To answer that question, would be to dignify an obvious response.
Incentive to join a clinical trial. As an involved person, you know the answer. I won’t be roped.
Thinking about the implications. If everyone contemplates the implications, very little would be done, including the use of the U S Patent Office whose work force would dramatically recede.
Nathan
First, to Anne’s point:
“Compassionate use would not be widely available b/c insurance does not generally cover it. Unfortunately, most people cannot afford to pay…”
That makes this elitist by nature, right? Only those rich enough to afford it can have access to the experimental drugs. This completely flies in the face of FPME’s point above when he says “This isn’t about access for the elite either.”
Now to Steve’s non-response. You really didn’t answer any of my question. You can say I’m being cold-hearted. I say I’m being practical. I don’t see any easy answers to the questions I posed.
1) If dying patients could get easy access to experimental treatments, then why should they enroll in the clinical trial? It doesn’t make any sense. I would shake the very foundations of cancer clinical trials.
2) What happens to the data (good OR bad) that comes from these patients that are using the unapproved drugs? Can/should the FDA take that data into consideration?
3) If the company charges huge prices for the drug, then they conceivably could make enough money simply through “compassionate use” and never actually COMPLETE a real, controlled clinical trial to prove efficacy. (this is especially true of small companies, which is where many of these experimental drugs originate)
4) Is the company COMPLELLED to supply the drugs to the dying patients, or is it up to their discretion? Remember that companies typically manufacture only enough drug to complete the clinical trial. Why should they spend millions of $$$ to make more GMP-quality compound? These drugs are cheap to make on a ton-scale for millions of people — but incredibly expensive to make small quantities of.
You can call me cold-hearted if you like — but these issues are very real. I’d love to hear some detailed responses to each of the points I raise. I don’t see any easy way around any of them.
NyHack
To further Nathan’s point, following on mine earlier… there is in fact a phase 1/2 MM trial underway with Tysabri. Patients in the phase 2 portion will be randomized and may not receive Tysabri. How could these patients be denied if Mr. Baron is allowed to receive the drug with the same condition?
It is also right to point out that while there are often instances where terminally ill patients receive a drug through compassionate use, it is rarely a drug in phase 1 development.
Steve
Nate
I have been involved with the biotech industry for many, many years and our democracy is based on a capitalistic structure.
I admit it may be unfair to those who can’t get any drug they want for nothing or because it’s in a trial, and they maybe do not have the close contacts to gain access to the therapies but, that is the unfortunate and only way our country works but for a few government underfunded health funds.
I would like to see everyone treated equally but that isn’t reality. We have created the American Way and so far, it’s a lot better than any other government on this planet.
Christopher
Steve - if you think the healthcare system this government has put in place reflects the best government on the planet you need to get out more. But as Ed says, this is a garden party and I shouldn’t bring up politics.
Former pharma Marketing Exec
Nathan and NyHack,
You are ASSUMING that if the patient gets the drug and develops PML, that it will prevent patients getting the drug within the confines of the clinical trial from further treatments.
That is the wrong argument. The FDA has given permission for this to go ahead and have obviously looked at the risks involved. The patient knows the risks, it does not jeopardize the clinical trial. It provides more data, but the experience of one patient will not stop the trial, especially when so many patients may, MAY, benefit from it.
As for the idea that patients in the MM arm can be randomized to not receive this drug, that is the way it goes. However, HOWEVER, in most cases if the drug is showing clinical effect in the arm for the patients getting the drug, with this type of critical disease, patients are allowed to cross over.
The article further states that at this time, there is no data on the use of this drug in Human trials. So, here is a chance to capture some firsthand data.
You can make a good point about this being an “elitist” issue, in my view, that is the only leg you have to stand on.
Yet, I know countless patients who are ordinary citizens and have jumped the cue. What can you say about those people?
So, we all partake in denying Mr. Baron access to this drug, based on baseless arguments, when really it seems to be more because he is a “somebody” and some of us just can’t handle that?
As for the update that Ed has provided, I rest my case, that was exactly what I said it was. The results of Mr. Baron’s experience cannot be lumped in with the rigorous clinical trial, but it does provide more data.
Nathan, your remark about FDA approval becoming meaningless, cracks me up. Are you sure you really meant that? Compassionate use as this is has been going on for a long time, and must continue. For the sake of the patients these companies try to make us believe they provide drugs for and try to help them prolong their lives.
Funny how Biogen figures they can pass up any opportunity to get more data…
The people at Biogen do not have the necessary skills to negotiate this issue, so they are blowing it off. Political posturing on Biogen’s part - they get no sympathy from me.
Steve
Chris,
I said the government is the best, not the health system being the best.
In fact, I stated,”underfunded health funds”.
By the way, my surmising has just become fact, Mr. Baron will get his drug therapy.
GeorgejjL
I wish Fred the best of luck and God’s blessings.
Tysabri seems to be wonder drug for MS patients and I am hoping that it will become a wonder drug for Multiple Myloma patients as well.
Gooe luck and God bless,
George
Questionable
“You are ASSUMING that if the patient gets the drug and develops PML, that it will prevent patients getting the drug within the confines of the clinical trial from further treatments.”
I don’t assume that, but I do assume that if Mr. Baron gets PML, this drug will be even more tainted with PML than it is now. And hundreds of Mr. Baron’s law partners will sue the heck out of biogen everytime someone develops PML, assuming this drug even makes it to market for MME. In case you haven’t noticed, the FDA is very focused on safety these days …
Former pharma Marketing Exec
Questionable,
It won’t be just Mr. Barons case, should he develop PML, that would bring down this drug.
This is a cancer drug. My understanding is that as long as the facts and risks are known and documented, then this drug could come to market with a BBW.
You cannot look at this case as some other class of drug. It is not a birth control drug for example. Developing PML as a side effect for a birth control drug would be unacceptable. There are other cancer drugs that cause CHF and a whole host of other life threatening problems.
I do think the data will be reviewed. But here is the catch, why are we willing to say that if a few people develop PML and the drug doesn’t come to market that we have done a great dis service to the countless thousand others who must or at least, should access this drug. Why can we think that the majority of these patients will not develop PML? Therefore, if that is the case, why bring this to the market for them at all?
In other words, denying him access on the basis that he MIGHT develop PML and that would be a disaster for all the other patients is not a strong argument.
vincent
The situation is more complicated with Tysabri, because it is currently available only under a strict prescribing and monitoring program called Touch; the program was instituted when Tysabri was brought back to the market in July 2006 after having been withdrawn in 2005 because of its link to a rare and often fatal brain infection called PML. Tysabri is now taken by an estimated 32,000 patients worldwide with multiple sclerosis and Crohn’s disease.
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Vincent
Drug Rehab