Wednesday, May 04, 2005

The Story Has 2 Sides - Amanda and Medarex

In his best-seller, “Blog”, columnist and talk show host Hugh Hewitt explained why blogs are passing news analysts in popularity: “The public has the final say. There is no going back, only an endless effort to capture and keep audience based on credibility.” (pg 94). That credibility is the seed for the blogosphere’s growth and character. Sometimes it’s vital for blogs to band together to defend a fellow blogger. Sometimes, it’s necessary for one blog to step in to be sure the story remains balanced.

Tuesday afternoon, Hugh Hewitt posted the story of Amanda Twellman-Dieppa, who contacted him to ask for support in her quest to gain access to an experimental cancer drug. According to Amanda, she has cancer which has relapsed, and in her opinion only an experiemntal drug she calls “CD30” has any chance of saving her life, but she says the drug company, Medarex, refuses to allow her access to the drug, even though she says the Food and Drug Administration has promised special permission to ensure she can take the drug. Hewitt checked our her website, decided he found it credible, and says he tried to get Medarex’s side of the story. By airtime of his radio show, Hewitt had made up his mind to pick a side, and pushed his audience to press Medarex to release the drug. One of Hewitt’s callers pointed out that he had only presented one side of the story, which Hewitt rather angrily denied, saying “she’s dying, and we can’t wait.” The caller suggested that one day wait to get the other side wouldn’t hurt the matter, and could allow a balanced presentation. Hewitt was not interested in that option. Hugh's one of the good guys, but on this call I don't believe he has covered all the bases. So, I decided to look into the matter myself.

Hewitt’s website has links to Amanda’s website (which has become unavailable, probably due to high traffic), and the website for Medarex. This allowed me important reference information, for which I thank Mr. Hewitt.

Hewitt began with Amanda’s statement to him, which in part reads as follows:

I am 22 years old and I have cancer. I was diagnosed when I was 16 years old, went through chemo and radiation and was in remission until I relapsed when I was 19 years old. I went through a grueling stem cell transplant and received my lifetime amount of radiation and once again went into remission until February 25, 2005.”

One thing which bothered me right off the bat, is that Amanda does not specify what sort of cancer she has in this statement. Since I was unable to access her website, it’s possible that this information is on her website, but neither Amanda nor Mr. Hewitt were specific about this point. This is a concern, because there are many types of cancers, some which move rapidly (like cancer of the liver) and some which grow comparatively slowly, some which can be treated with a number of options, and some which are difficult to treat.

Another point of concern showed up when I reviewed the information at Medarex. Medarex did not refer to a drug called “CD30”, but their 2004 Annual Report mentioned promising hope for a drug they called “MDX-60”, which is primarily being developed as a treatment for Hodgkin’s Disease, and the statement says the drug was especially effective in treating “relapsed CD-30 lymphomas”.

The National Institute of Health identifies “CD 30” not as a drug, but as a class of treatment, called “anti-CD 30 immunotoxins for the treatment of cancer”, specifically “a novel therapeutic agent to treat Hodgkin's disease and anaplastic large cell lymphoma, NCI has made a panel of recombinant immunotoxins specific for CD30 using Fvs of newly produced anti-CD30 monoclonal antibodies (MAbs) and a truncated mutant of Pseudomonas exotoxin. CD30 is highly expressed on both Hodgkin's disease and anaplastic large cell lymphoma. NCI is curently seeking cooperative partners to work with the Laboratory of Molecular Biology in the development and clinical application of immunotoxins directed against CD 30 epitopes found on cells in Hodgkin's Lymphoma and anaplastic large cell lymphoma.

Significantly, the NIH says that anti-CD 30 immunotoxins are in a “current state of development” known as “in-vitro demonstration of toxicity.

Further, the NIH notes that in developing drugs for this purpose, companies working on the drug will operate under an agreement known as “CRADA” (Cooperative Research and Development Agreement) . CRADA terms include:

* Term of the CRADA will be up to five (5) years
* No funding from the Government is available to Collaborator under a CRADA.
* Non-exclusive license option available for background rights. Exclusive license rights may be available in a specified field of use.


In plain english, the NIH expects drug labs to develop the drugs, but at their own cost and risk, and without a guarantee of an exclusive license, should a viable drug be discovered.

Looking deeper into Medarex, I found that Medarex began in 1987 as a New Jersey company, went public in 1991, and specializes in Monoclonal antibodies. Their specialties are “MDX-10” for melanoma treatment, and “MDX-60” for Hodgkin’s Disease (both entering or in “Phase II” of clinical trials in 2005)

22 “UltiMAb” products in clinical trials in 2004. Eight reached Phase II or III, meaning most of their work is in very early stages.

"MDX-60" is the product used in conjunction with “relapsed CD-30 lymphomas”, in Phase I and II trials. This is the product most likely referred to by Amanda Twellman-Dieppa.

"MDX-10" is already in “fast track” study in conjunction with the FDA, for treatment of metastatic melanoma, meaning that "MDX-60" has a back seat..

FDA assigned “Orphan Drug” designation for "MDX-60" in treatment of Hodgkins Disease. This means that using the drug for any other purpose can result in revocation of this designation, with significant tax penalties for the company.

Also, I found a “2005 Proxy Meeting Notice”, which shows company will have a meeting of the Shareholders on May 19. The notice specifies that any actions the company may take before the May 19 meeting, will be decided and approved at a prior meeting on March 22, 2005.

So, if you’re a director at Medarex, here’s what you see:

You're a relatively new, relatively small comany which has two major drugs in various phases of advanced research, but neither is in anything like near-release stages, certainly not for FDA submission. A woman and her family are demanding you release a drug still in “in-vitro” testing to them, and this request does not come from the FDA or the woman’s doctor, and there are no effective releases from liability, should something go wrong (like a patient facing death in a year, suddenly dying from an unexpected heart attack). There is no information about whether “MDX-60” is the only drug with a reasonable chance of success, nor in fact any empirical data to show “MDX-60” will be effective in the specific case. Further, release of the drug will be public record, so it’s success or failure will provide pivotal data to your competitors. Even if the drug does work, there is a risk that the extended use of the drug would result in increased tax costs, which the eventual sale of the drug would not cover. And finally, you have no authority to make a decision between March 22 and May 19, because of a blackout window in the Shareholders’ Meeting terms. In those conditions, what would you say to Mr. Hewitt, if you represented Medarex?

Maybe Medarex can find a way to make this work. Maybe there is some negotiating position with the FDA which can happen. But Hewitt’s assumption that Medarex doesn’t want to help Amanda, or that Medarex is operating out of greed, does not fairly present both sides. This article presents Medarex’s side, to give some balance to this story. It also reminds us that as bloggers, we have a strong and unending responsibility to seek the truth. It also, as a sidenote, illustrates some of the difficulties in drug reform initiatives: We need to focus on the patients, but never to the point of forgetting the needs of the companies which provide the miracle cures we now take for granted or worse, expect on our terms without delay or conditions.


UPDATE: The "Save Amanda" site is back up, but is very thin on facts. Amanda and her family still do not explain what sort of cancer she has, there is no medical support whatsoever, least of all to explain why MDX-60 is alleged to be the "only" drug which has any chance of successful treatment. I have also emailed Mr. Hewitt the notice of this article, so that he will have fair opportunity to respond.

UPDATE II: As it happens, I cross-posted over on Polipundit. Some of the more salient comments follow:

a4g reported (9:26 AM) that at the end of his show on Tuesday, Hugh spoke with Amanda’s father, who says that he has spoken with the President of Medarex, and found him very kind and sympathetic.

I pointed out (9:54 AM) that “the reason I am concerned about the absence of a doctor’s comments, is that we have nothing to indicate that MDX-60 will be more effective than other options. Amanda says MDX-60 is ‘it’, but given the level of its development, that seems an emotional assumption, rather than the judgment of a medical professional.
Next, what if MDX-60 kills her immediately, then it turns out another drug could have saved her? If Medarex ignores protocols here, there are all sorts of liability and performance issues that can fall on the company. What good would it do to give Amanda the untested drug, if the result not only does not save her life, but destroys the company and hurts countless other people, because the research is set back by the loss of the company? Don’t say it can’t happen, because it’s happened before.
Finally, there is a basic issue of fairness here. Hewitt put this up on his national radio show, but only addressed one side of the story. I genuinely hope that Amanda can receive the treatment that will save her life, but to coerce a private company to take risks, purely on an emotional argument with no empirical support at all, can hardly be called the right way to go about this.”


~B observed (9:58) this raises the question of whether it is acceptable for “dying patients to demand access to unproven drugs in an effort to extend and or save their lives at the risk of crashing the company developing the drug.”

Buckland (10:20) observed “The part I don’t like about this is the perception it leaves – if you want an unapproved treatment, the way to get it is to scream loudly and make accusations. Working within the system is for losers (and eventually dead ones).
The FDA puts some really stringent rules in place concerning the hurdles that a drug has to clear in order to come to the public. This is why it takes many years and successful trials to bring the drug to the public.
The drug has to be safe and effective. Those concerns have to be balanced. OxyContin is a great pain reliever, but the safety is less than optimal due to high addiction rates. However on balance it’s good. Such tradeoffs are made by companies and the FDA hundreds of times per year. There are exceptions, but on balance the system works well.
My guess is that the company will work out a way for Amanda to get the medicine, possibly through enrolling her in a trial of some kind. It may or may not do her any good, and it may or may not have side effects...

Non-Hodgkins Lymphoma (NHL) is extremely rare in people under 50, while Hodgkins Lymphoma is much more common in young people. However the fact that she had a marrow transplant hints that it is NHL, since that’s the only form of lymphoma that a transplant does any good for. It’s not an accepted treatment for Hodgkins Lymphoma.
Another possibility is that she has the more common Hodgkins Lymphoma and the family convinced the doctors to experiment with a marrow transplant (she calls it stem cell transplant), even though it has no history of working on Hodgkins Lymphoma. That would explain the public pressure to get the “wonder drug” now, and also explain why there’s no definitive statement on the type of cancer on the website.
My heart goes out to the family. It seems that they’re thrashing about, trying to find a cure for their daughter. Maybe I would do the same. However pushing for treatments that won’t help won’t do any good for anybody. And publicly pushing for drugs that aren’t ready for the public will tend to dry up the supply for those who really need them.”


I followed up again (10:46) with unanswered questions: “Why is MDX-60 the only option?
Why should a drug in early stages of testing be released to a patient with no compatibility vectors considered?
The page you referenced clearly (and in bold letters) claims Medarex is “CHOOSING PROFIT OVER LIFE” without a shred of evidence to back up that claim. Why do you ignore that issue?
There is not a single piece of medical opinion anywhere. There is nothing from her GP or any Lymphoma specialist, to support her demand for this specific treatment regimen. Why not?”


Buckland observed (11:04) “According to the Lymphoma Information Network , there are roughly 131,279 cases of Hodgkins Lymphoma in the US. All are fighting their own demons and those of the medical industry in order to do what’s necessary to survive. Each can tell a story of a disinterested doctor or a treatment that didn’t work as expected.
So if Hewitt found a new demon in the form of a drug company, so be it. And getting a new drug with unknown efficacy and side effects may be just what she needs. But if this in any way delays research on this or other drugs by diverting scarce resources to her above all of the other 131,278 cases then it’s a bad thing.
In the 1980’s the organ transplant world went through this. A reasonably fair system was set up for the allocation of scarce donor organs. However “resonably fair” is not at all fair if you are the one denied a life saving organ. So very sad cases mounted publicity campaigns, complete with sobbing Moms and beautiful children to get the needed organ.
And it worked. The cases that could mount the best publicity drive got the livers, no matter where the need was. Eventually the system corrected and went back to more of a dispassionate approach to these horrible choices.
There is a very good case that drugs as a whole go through too many trials before reaching the consumer. There’s also a case to be made that certain specialty drugs should be exempt from more (they are somewhat exempt now) of the rules and regulations. However I’m hard pressed to come up with a logical argument that the people who can get on the radio or build a website should go to the front of the line
.”

Jim m noted (11:47) “A couple of thoughts…I have worked in the oncology/transplant industry for 14 years now. Stem cell transplants(Bone marrow is almost never used any more as the primary source of cells) are done for Hodgkins Lymphoma. It is rare. Most cases respond well to therapy and such aggressive therapy is not necessary.
The company’s reluctance is quite understandable. “Compassionate Use” exemptions from the FDA are common, however these are typically requested by physicians who are participating in a company sponsored study. The Medarex website indicates that MDX-60 is in Phase II trials, but does not specify whether or not these trials are active or complete. In any case is seems clear that Amanda’s physician is not participating in any Medarex trial. Also it would take longer than just a few days to get the drug to Amanda. While the company might e able to ship the drug, the hospital where she would be treated would have to have any treatment plan approved by their investigational review board and the physician and staff need to be trained in the drug’s use. These issues would delay administration of the theray significantly.
The idea that the company is being greedy is simply nuts. They are required by law to follow very strick regulations regarding the use of an unapproved drug. Improper release of a drug would bring severe penalties to the company and possibly delay the approval of the drug if trials are successful.
As to the notion that this is her only hope. Please go to www.clinicaltrials.gov and search for hodgkins lymphoma. You will find 101 open trials for this disease. Many are for advanced disease. This family as seized upon one opportunity among many and clearly has decided not to pursue the many other options that are currently available.”


These profound thoughts add great value to this matter.

2 comments:

jon said...

I was looking at your posts about cancer kidney and found a good article about the same cancer kidney info too...

God luck with it : )

wholl resources said...

Looking for skin cancer mole picture information I came across this post. I totally agree with you and would feel the same way!

jon