Monday, December 29, 2008

FDA/CDER "no answer" answer to my request about when Stellara will be approved

I just received my third FDA unhelpful response that can be summarized in real people speak in the following sentences: "Sorry we cannot help you." "We refuse to tell you when the NOVEL medication with "stunning" clinical trial results will be available to your son." "We only help pharma companies." "Real Americans can go sit and in a corner and die for all we care as long as our jobs are protected. "

But even more amazing is that after three of these FDA/CDER no help emails, FDA CDER sent me a customer satisfaction survey. Yes, they asked me how I felt about their "service."

What fun it was to fill out their survey! I know, I know, no one will read it, but somehow it was satisfying to write down what I felt. You can read my response to their survey at the end of this post.

But first I thought I would provide you with the pleasure of reading the FDACDER's third and most recent response. I wrote to them asking about the delay in approving the REVOLUTIONARY advance in the treatement of psoriasis namely Centocor's Stellara aka Ustekinumab aka CNTO 1275. (Ever wonder why all these new investigational meds have three names?)

The FDA/CDER email is in red and my translation is in blue.

Dear Mr. Welch,

Thank you for writing to the Division of Drug Information in the Center for Drug Evaluation and Research (CDER). Please note that under the Freedom of Information Act (FOIA), the U.S. Food and Drug Administration can only provide information on approved drug product applications. (We will only give you info on medications that are already approved and in your local pharmacy. Information that any internet search engine can find quicker and again ONLY information about Meds that a doctor can ALREADY prescribe. Meds NOW on the pharmacy shelf. Meds that Paul has tried that did him little or no good-some even harmed him --bloody hives, breathing shut down.) Any information on an application submitted by a firm to the FDA, that did not receive approval, belongs to the manufacturer/sponsor developing the drug (21 CFR 314.430) so this type of information is not available from the FDA. (We know, but we won't tell you. You, stupid parent, thinking you have any political pull or importance to anyone at the FDA. You should know that ordinary Americans without political and financial influence are of NO import to us.) However, you may wish to contact the manufacturer/sponsor directly to inquiry about this product -- including the status. The manufacturer/sponsor is the source that can provide you with information on its product. (We are pretending that the manufacturer would actually give you information. We know they will not but by saying "CAN PROVIDE" we make it appear that there is a way to get the information, but of course we know they will not and we do not care.)

In addition, there is a mechanism (Compassionate Use) to access products that have not been approved. However, this would involve a physician willing to file a single patient or emergency Investigational New Drug (IND) application and this must be done with the cooperation and permission of the drug supplier. (This is a hours or even days long mind numbing process of ridiculous paperwork put in place to protect FDA bureaucrats first and foremost with no thought to getting the med to patients in need in a timely manner. Furthermore most physicians have no knowledge of new drugs in the pipeline. So they are scared even annoyed to be asked. The application puts all the risk on the doctor. What doctor is going to accept the risk of losing his profession for one patient? Finally even if the doctor is some kind of saint, accepts the risk and spends the hours needed to comply with all demanded records (the patient's med records and the doctor's education and experience records) and fill out the data demanded by the FDA, the Pharma company HAS THE FINAL SAY. That is correct. The company developing the med can and always does say NO. NO. NO. NO. That is it. No appeal. When the pharma company says no, their "no" is absolute with no way out and no appeal. Not even the courts will let you have the med. Court case after court case gives one and only final say EXCLUSIVELY to the company EVEN WHEN THE PATIENT WILL DIE WITHOUT THE MED. That's right. You can have a life threatening infection and the only antibiotic that will save you is not yet FDA approved, then YOU DIE with NO ACCESS and no right to sue.) For more information accessing unapproved products and single patient/emergency IND, please visit the sites at and

Lastly, FDA has a role in facilitating appropriate treatment access to investigational drugs, while at the same time recognizing the need to protect the public by requiring that drugs are proven to be safe and effective before they may be generally marketed to US consumers. The agency is committed to making effective therapies available to patients in need and continues to offer access to unproven therapies through our special access programs (as explained above). (LIE! BIG FAT LIE!)

Sincerely, Division of Drug Information LL Center for Drug Evaluation and Research Food and Drug Administration (NOTICE there is no name. The monster and liar who wrote this was too ashamed to put his name on it.)

This communication is consistent with 21 CFR 10.85 (k) and constitutes an informal communication that represents our best judgment at this time but does not constitute an advisory opinion, does not necessarily represent the formal position of FDA, and does not bind or otherwise obligate or commit the agency to the views expressed. (More CYA babble by the coward who wrote the rest of this letter)

My response that I gave them for their satisfaction survey is reproduced below.

My son has been an un-oiled, frozen Tin Man like in own personal version of a Wizard of Oz horror for last four years. And for at least the last two years a medication to help him has been tied up by the FDA.

Don’t BS me about compassionate use. Compassionate Use is neither. There is no compassionate from pharma nor do they allow any use. We have tried for 18 months to get access. The answer always is NO. NO. NO!

Clinical trials are a scam. They are not run on scientific principles to get the best possible knowledge. No, they are narrowly set up to get skewed results in hopes of getting FDA approval. Exclusionary and inclusionary criteria are written to eliminate all risk or any event that might further delay the glacially slow FDA approval process. They are not set up to get good science.

Worse the sickest patients like my son who will be first in line when investigational drug is finally FDA approved are deliberately excluded from the clinical trials. My son has been excluded from TWO clinical trials because his symptoms were TOO severe. Clinical Trials as currently concocted give NO data on the truly sick for doctors to look at when prescribing.

When "stunning" breakthroughs with NOVEL medications in clinical trials do happen, you folks delay, delay, delay. Do you think it is humorous to contemplate all the suffering and tortured patients waiting and dying while you delay MAJOR BREAKTHROUGHS?

APPROVE USTEKINUMAB/STELLARA NOW! It has the potential to allow my son to move again. How long will you %$#&@@!! make my son sit in a wheel chair while you play protect your backside games.

If FDA Commissioner, Andrew C. von Eschenbach, did not want to do any work at the job of running the FDA, why did he take the job?

Friday, December 26, 2008

Fix our B cells, Cure Autoimmune Disease

More evidence that a small subset of our B cells are responsible for keeping the autoimmune process going. B cells are the cells that produce antibodies that give us immunity to childhood diseases. Those are among the 80% of our B cells that are the "good guys". We cannot live without B cells manufacturing very specific antibodies for the various pathogens "germs" we encounter throughout our lives. Yet there are some B cells that if not suppressed produce antibodies that attack our own tissues and give rise to the 80 or so named autoimmune diseases examples of which are Rheumatoid Arthritis, psoriasis, Psoriatic Arthritis, Lupus (SLE), Multiple Sclerosis, Scleroderma, etc.

Good News is that there is an FDA approved drug, Rituxan, that can get rid of all the mature B cells. Unfortunately both "good" (protective) and "bad" (autoimmune causing) are eliminated. Losing all the "bad" B cells can turn off our autoimmune disease for weeks to years.

More good news is that the "baby" B cells (immature) are unaffected by Rituxan and they rapidly mature into fully competent "adult" B cells that will protect us against infections.

Bad news is that during the interim between the Rituxan caused death of all the mature B cells and the development of the unaffected "baby" B cells into fully competent "adult" B cells, there is a window of vulnerability to disease and infections for the patient.

Worse news most of us are carrying dormant viruses can become reactivated if the immune system is disabled even temporarily.

The very worst news some of those viruses can kill us if our immune system lacks mature B cells to keep them in check.

The most feared and the most deadly of these dormant horrors is a brain virus with the innocuous initials of PML. Sadly the P stands for Progressive which basically means unstoppable. The M stands for multifocal which means lots of location all over the brain. Worst of all the L stands for Leucoencephalopathy--white patches of dead brain tissue. PML is VERY deadly. I believe the survival rate even with the best possible current medical care is less than 10%. The hidden and undetectable presence of this virus makes any B cell depletion therapy a little scary.

Too bad Rituxan targets all our mature B cells both the kind that protect us from infection and dormant viruses as well as the "bad guy" B cells that cause autoimmune.

Wouldn't it be nice if only the bad guy B cells could be targeted?

What we need is a way to kill only the autoimmune B cells and not the good guy B cells. So far no one has done that even in the research lab.

Or find a way to 'tame' the bad autoimmune B cells, so they no longer act like bad guys. Taming them is very possible and has been done repeatedly in the research lab--both with various kinds of vaccines and with manipulations of immune system to produce more cells that calm down the immune system. The cells that calm down the bad guy B cells are called T regs. T-regs? Yes T regs. No it is not that scary dinosaur with big sharp teeth. The name just sounds a bit like T rex, but T regs are very different. They have the ability to turn off autoimmune disease. Apparently a signal called Interleukin 10 (IL-10) controls their numbers and effectiveness.

Lots of really nifty ways to increase IL-10 from a little bit gross--genetically engineered gut bacteria to pretty darn gross--good old fashioned parasites (hook worms, whip worms) to over the top gross out--fecal seeding of our colon with bacteria from a healthy donor. Fecal seeding means just exactly what it sounds like! The intestinal worms and the fecal bacteria from a healthy donor both seem to produce IL-10 or a biologically similar substance that our bodies use as though it were IL-10. IL-10 in small amounts in the right places increases our T regs and helps them to be better at controlling bad guy B cells.

Another way to deal with the overactive autoimmune B cells is to find a way to decrease their activity. The following article describes an FDA approved drug, bortezomib, for cancer that seems to interfere with B cells that are over active and stop them If you have an active case of autoimmune disease, then the B cells that are most active are likely to be the bad guy auto-antibody producing ones. Turn them down and the autoimmune disease should get better. Unless of course you are fighting an infection then turning off the active B cells would turn off the good guys that are most active in the infection fight. Not good. You must not be sick if you take this medication and you probably should stay away from sick people while you are taking it.

Here is the article from
(1. Plasma cells are B cells. 2. Because autoimmune disease is basically us rejecting parts of our own body, any drug that stops organ(kidney, heart) transplant rejection) will also stop autoimmune disease.)

Cancer drug effectively treats transplant rejections

CINCINNATI—University of Cincinnati (UC) researchers have discovered a new therapy for transplant patients, targeting the antibody-producing plasma cells that can cause organ rejection.

Results of the study are published in the Dec. 27, 2008, edition of the journal Transplantation.
Steve Woodle, MD, and colleagues found that a cancer drug—bortezomib—used to treat multiple myeloma, or cancer of the plasma cells, is effective in treating rejection episodes caused by antibodies that target transplanted kidneys and reversing rejection episodes that did not respond to standard therapies.

B-lymphocytes, or B cells, play a large role in the humoral immune response by making immune proteins ( these are antibodies) that attack transplanted organs.

"We found a body of literature demonstrating that bortezomib works well in suppressing transplant rejection in the laboratory," says Woodle, lead author of the study and chief of transplant surgery at UC. "Moreover, it worked well in models of autoimmune diseases."
T-lymphocytes, or T cells, are white blood cells that were commonly thought to cause the rejection of transplanted organs.

Woodle and his team began searching for agents that targeted plasma cells in 2005.
"It has become clear that plasma cells and the antibodies they produce play a bigger role in rejection than previously thought, and the development of therapies targeting these cells has lagged," he says. "We realized that current therapies don't target the plasma cells which may produce the antibody, in general."

Researchers administered this drug to six kidney transplant recipients with treatment-resistant organ rejection, evaluating and recording their responses to the treatment.

In each case, treatment with the drug provided prompt rejection reversal, prolonged reductions in antibody levels and improved organ function with suppression of recurrent rejection for at least five months.

Jason Everly, a board-certified oncology pharmacist in the division of transplant surgery at UC and co-author of the study, says the toxicities associated with this drug were predictable and manageable and were much less than those associated with other anti-cancer agents.
"We are pleased to see its toxicities are similar in transplant recipients suffering from treatment-resistant mixed organ rejection," he adds. "We hope it will be a viable therapeutic treatment option in this patient group."

Woodle says although this data is promising, it is difficult to overestimate the implications of this drug.

"We have an immunosuppressive agent that for the first time can target antibody-producing plasma cells with an efficacy similar to drugs that target T cells," he says. "This has significant implications for transplantation and auto immune disease."

UC researchers are currently conducting four industry-supported clinical trials to expand these findings.

This research was investigator-initiated. In addition to grants,
researchers have received honoraria from the manufacturer of bortezomib.

Tuesday, December 23, 2008

URL for Advances in Drug Discovery blogspot

I found an interesting blog today. It is not strictly about autoimmune disease but our problems are mentioned. The blog is called Advances in Drug Discovery and its URL is:

The blog discusses leading edge discoveries in the field of pharmaceuticals.

Sadly the last entry is June 2008, so it may be a dormant blog.

Monday, December 22, 2008

Ustekinumab delayed AGAIN by the FDA

Last Friday the FDA in again delayed the most significant advance in the treatment of autoimmune disease in last five years. The drug called CNTO1275 in research labs, Ustekinumab by doctors and Stelara by patients.

This drug, Ustekinumab, had "stunning" results according to independent observers in human clinical trials announced in Spring of 2007.

When I first read of the results, I naively thought that the FDA would rush this new drug to the market. After all Ustekinumab targeted a part of the immune system that no other drug targeted. It was new. It was novel. It was remarkably efficacious. I thought FDA would have it approved by summer of 2006.

But no. The FDA required the drug manufacturer to turn in a Biologic License Application. It took Centocor the manufacturer until Dec 5 2007 to get application in order. It took the FDA until March 2008 to DECIDE to accept the application. It took until June of 2008 to get together a outside science panel to review data. The independent panel recommended UNANIMOUSLY to approve the medication. FDA sat on the recommendation for six weeks then announced they would delay another four months until December 2008--TWENTY MONTHS AFTER THE STUNNING RESULTS IN 2006.

My son has been crippled and frozen sitting in a wheel chair for all those twenty months. Now the FDA rhymes with DELAY. DELAY. DELAY. has postponed approval AGAIN! B@$TARDS! I wish those evil monsters could spend one day in my son's place. Just one day of pain and terrible limitations needing help to do every single necessity of daily life. PIGS! I need a shoe to throw at their heads.

Did I mention in September of 2008 clinical trial results were announced indication that Ustekinumab beat for efficacy the number one drug on the market (Enbrel) for my son's conditions (psoriasis, PsA, AS) in head to head trials?

Is someone getting at the FDA getting paid off to delay this drug?

Read the article here:

FDA Holds Off Decision on Johnson & Johnson (JNJ) Psoriasis Drug
12/19/2008HORSHAM, Pa., Dec. 19 /PRNewswire/ --

Centocor, Inc., announced today that the U.S. Food and Drug Administration (FDA) issued a Complete Response letter for its Biologics License Application (BLA) for ustekinumab. The application, filed by Centocor in late 2007, seeks approval to market ustekinumab as a subcutaneous biologic therapy for the treatment of adult patients with chronic moderate to severe plaque psoriasis.

The Complete Response letter requests additional information, including a proposal by Centocor for a Risk Evaluation and Mitigation Strategy (REMS). FDA requires REMS to ensure that benefits of an investigational or marketed treatment outweigh the risks. The ustekinumab REMS must contain a Medication Guide and communication plan. It does not require restricted distribution. The FDA has not requested any new non-clinical or clinical studies evaluating the efficacy or safety of ustekinumab prior to approval.

"We are confident that we can expeditiously address the questions set forth in the Complete Response letter," said Jerome A. Boscia, M.D., senior vice president, Clinical R&D, Centocor, Inc. "We anticipate responding to the FDA in January 2009 and remain focused on bringing ustekinumab to market and ultimately to appropriate patients living with psoriasis and in need of treatment."

On June 17, 2008, the FDA's Dermatologic and Ophthalmic Drugs Advisory Committee (DODAC) unanimously recommended ustekinumab for approval. DODAC is convened on request of the FDA to review and evaluate safety and efficacy data of human drug products for use in the treatment of dermatologic and ophthalmologic conditions. The committee provides non-binding recommendations based on its evaluation; however, the FDA makes the final decision on approval of the drug.

About Psoriasis
Psoriasis is a chronic, immune-mediated disease, which results from the overproduction of skin cells, resulting in their accumulation on the surface of the skin, which causes red, scaly plaques that may itch and bleed. It is estimated that approximately 7.5 million people in the United States and 10 million Europeans are living with psoriasis and nearly one-quarter of those people have cases that are considered moderate to severe.

About Ustekinumab
Ustekinumab is a new, human monoclonal antibody in Phase 3 development by Centocor, Inc. for the treatment of moderate to severe plaque psoriasis, and is being investigated as an infrequently administered subcutaneous injection. Ustekinumab is a new, human monoclonal antibody with a novel mechanism of action that targets the cytokines interleukin-12 (IL-12) and interleukin-23 (IL-23), naturally occurring proteins that are important in the body's regulation of immune responses and that are also believed to play a role in inflammatory disorders, including psoriasis.

On November 21, 2008, the European Medicines Agency's (EMEA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion for ustekinumab for the treatment of moderate to severe plaque psoriasis in adult patients who failed to respond to other systemic therapies.

On December 12, 2008, the Canadian Health Authority approved the use of ustekinumab for the treatment of chronic moderate to severe plaque psoriasis in adult patients who are candidates for phototherapy or systemic therapy.

Centocor discovered ustekinumab and has exclusive marketing rights to the product in the United States. Janssen-Cilag companies have exclusive marketing rights in all countries outside of the United States.

About Centocor, Inc.
Centocor is harnessing the power of world-leading research and biomanufacturing to deliver innovative biomedicines that transform patients' lives. Centocor has already brought innovation to the treatment of Crohn's disease, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, ulcerative colitis, pediatric Crohn's disease and psoriasis.
The world leader in monoclonal antibody production and technology, Centocor has brought critical biologic therapies to patients suffering from debilitating immune disorders. Centocor and Janssen-Cilag are subsidiaries of Johnson & Johnson.
CENTOCOR DISCLOSURE NOTICE: This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or unknown risks or uncertainties materialize, actual results could vary materially from Centocor's expectations and projections. Risks and uncertainties include general industry conditions and competition; economic conditions, such as interest rate and currency exchange rate fluctuations; technological advances and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approvals; domestic and foreign health care reforms and governmental laws and regulations; and trends toward health care cost containment. A further list and description of these risks, uncertainties and other factors can be found in Exhibit 99 of Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended December 30, 2007. Copies of this Form 10-K, as well as subsequent filings, are available online at, or on request from Johnson & Johnson. Centocor does not undertake to update any forward-looking statements as a result of new information or future events or developments.
Source: Centocor, Inc.

Saturday, December 20, 2008

Rituxan, B cell depletion therapy proved efficacious again!

Rituxan (MabThera in Europe) has again been found to significantly reduce symptoms of autoimmune disease. The newest clinical trial results are for Rheumatoid Arthritis. Previously it has been found to be helpful for MS and Lupus. Read the new clinical trials article here:

B cells are our memory cells and they are the cells that produce antibodies. They are a kind of white blood cell. We have tens of millions of them in our body especially in the dry skin (epidermis) lining the outside of our body and the wet skin (mucous membrane) that lines the inside of our mouths, throats, intestinal tract, nasal passages, and the "plumbing tubes" or our urinary and sexual organs--urethra, ureters, vagina, uterus, fallopian tubes.

Immature B cells are being constantly produced in our bone marrow and released into the body where they mature. They are a vital part of our immune system. Without them we would quickly die of infection. As they mature they develop a CD 20 protein/receptor on their surface. Rituxan attaches to this receptor and labels the B cell for death. Other immune cells then kill the B cells. Good news is immature B cells do not have this receptor and are not killed by Rituxan. Given time (months) they mature and take the place of all the mature B cells killed by Rituxan.

The B cells lining the "outside" surfaces of our body both dry and wet work closely with another kind of stationary white blood cell called a mast cell of which equal million are found at these "outside" surfaces. The B cells produce antibodies and cytokines which can activate mast cells resulting in destruction of foreign pathogens (good) or destruction of patients own tissues (bad). The destruction of your own tissues is called autoimmune disease.

B cell are intimately involved in the autoimmune process in another way as well. They are the source of autoantibodies which independently attack “self” tissues while labeling those tissues for futher attack by dendritic and T effector cells. Some of our B cells are"bad" B cells. These B cells keep the autoimmune "pot" at constant "boil" by producing the autoantibodies. When the B cells are depleted with Rituxan or other B cell depleting medicines the autoantibodies are eliminated, in most cases the autoimmune disease stops. That is the good news.

The bad news is the only med FDA approved so far is Rituxan aka MabThera. It destroys all B cells including the ones that make and remember the antibodies to childhood diseases like measles and chicken pox. When all B cells are destroyed with this kind of med, the patient is no longer immune to a whole host of disease that the patient formerly was immune to. Viruses are a special problem. The patient may need a new set of child hood vaccinations after B cell depletion therapy.

More bad news, many of us carry hidden, suppressed viruses inside our bodies including herpes that causes cold sores, JC virus (jvc), CMV (Cytolomegalovirus) and worst of all the PML virus. PML stands for Progressive Multifocal Leucoencephalopathy. Without B cells these viruses can become reactivated. PML is especially bad. It can become an untreatable brain infection that is almost always fatal. No one can predict who will get PML after a Rituxan infusion. The incidence is quit low less than one in a thousand but it is a very horrible potential consequence of Rituxan.

Hopefully future research will allow only autoimmune antibody producing B cells to be destroyed eliminating the danger of PML and the need for re-vaccination for childhood disease of patients who are infused with B cell depletion drugs.

Dr. Ken show wrap up

Frank Burroughs and I were on the Dr. Ken Kronhaus Good Day Health program this morning as a part of the Doug Stephan Good Day show.

It went pretty well. Frank was awesome. I was a bit too rehearsed. There was so much I wanted to say and so little time. It is also surprisingly difficult to talk in quick accurate sound bites. Communicating on the radio is far harder than I imagined it would be.

Here are my followup emails to the various participants thanking them for their time. I hope many of you have a change to thank the participants as well for bringing the problem of the lack of access to life changing and life saving medications to the attention of an American radio audience.

Dear Frank
You were great! I am so glad you agreed to be on the show.

I think I am just too emotional. I spend hours preparing. I have stacks of flash cards with notes. So much to say so little time. Believe it or not I actually practiced what I wanted to say. Maybe too much.

How does a person get years of frustration, anger and sadness at the system and the delays into short coherent sentences? The delays have cost Paul so much.

I thought Doug Stephan was very helpful as well. He was pro-getting drugs to market. Dr. Ken less so. The thalidomide precedent has so affected our culture of getting new drugs to market.Everyone involved is terrified that they will get the blame for letting the next thalidomide on the market. Physicians, FDA bureaucrats and big pharma are too frightened of that one mistake that could cost them everything. The laws really need to be changed to give them protection so they can be more courageous.

Thank you again for your wonderful work. You remain our family's hero. The one shining hope in the midst of the constant stream of hurdles and barriers put up between my son and the help he needs.

I wish we could have brought up Jacob Gunvalson's lost of injunctive relief for access to PTC 124 by the third district court of appeals. I followed the case in the news. Poor Cheri.

Sometimes, I think there is a book here--a compelling book of patients and their loved ones desperately seeking game changing medication and therapies that are locked away in a research lab. In the case of my son, the med he needs, Ustekinumab, is in clinical trials here in San Diego County less than thirty miles away sitting in refrigerators but denied to him. He did not qualify for trials--too sick. It is a kind of terrible mental torture knowing that the medication is so close.

Most Americans have no idea of the type of revolutionary cures available in research labs and clinical trials. And they certainly have no idea that these meds are denied to the very sickest Americans who need them most.


Dear Dr. Kronhaus,

Thank you so much for having Frank Burroughs and I on your show this morning.

Changes in FDA clinical trial rules and lack of access to medication for the sickest Americans in a subject that most Americans are unaware of until they or a family member is denied life changing and life saving treatment—too late to do anything about the problem.

It is outrageous that our family has to consider traveling thousands of miles to Canada to get a medication that sits in a refrigerator less than thirty miles away from us in San Diego. Our son could not get passed the exclusionary criteria for that San Diego clinical trial. He had the right condition that was being tested, psoriatic arthritis but also has the related condition ankylosing spondylitis. He was too sick with autoimmune disease to qualify. A trip to Canada would be excruciating for our son. He is in constant pain. He uses almost thirty ice compresses a day. He is frozen up. I am not sure he could survive the trip. Is this what medicine has come to in America?

As to your expressed concerns about unexpected side effects, we are aware of that possibility but the disease effects must have equal consideration. His current life is no picnic.

Inclusionary and exclusionary criteria have been narrowed by pharmas companies in an attempt to protect the results of clinical trial from having any unexpected adverse problems. This narrowing has resulted in shortages of qualified volunteers. If trials were open up to more patients, cures would come faster not slower. Lack of qualified volunteers is now a limiting factor in trials. Yet thousands want access. Can we not find a way to solve both problems?

No one wants to get rid of safeguards in scientific process of testing drugs, we just ask that the process be streamlined and be a little compassionate for the very sick.

Peter Welch

Dear Doug

Thank you so much for giving Frank and me air time to discuss the unbelievable problem of access for sick patients to revolutionary new medication and therapies. People I tell about the problem just cannot believe it's true. They think there has to be a way to get these meds. But they are wrong. Compassionate use is a cruel hoax and access to clinical trials is denied for the sickest patients by exclusionary criteria put in place by Pharma companies.

The number one goal of the company is profit. Profit comes from the quickest possible approval of a new med not from helping sick Americans have greater access. Letting sick patients in or allowing compassionate use might result in some adverse event that slows down the already too slow approval process. I do not blame the pharma companies they are playing the game by the rules that are in place. Hopefully tom Daschle, Obama's appointee for Secretary of Health and Human Services will be a rule changer

I do blame the FDA for its antiquated rules and procedures. I especially blame the current FDA commissioner Andrew C. von Eschenbach. He has done nothing to improve access. Henry Waxman's House Oversight Committee wrote a letter to him a year and a half ago complaining about this very problem among others. Von Eschenbach forgot that it was his mandate and the mission of the FDA to improve the health of Americans first and foremost. He seemed to think that protecting FDA bureaucracy and big pharma company exclusive hold on these new cures were his number one and only job. Those considerations should have been his last priority. For the last six or eight months he seems to be just riding out his job, going through the motions waiting for the next commissioner to be appointed. Very sad.

Thank you again for bringing this the matter of access to the air.

I had practiced what I was going to say--over and over. Maybe too much I wanted to say so much more. I had flash cards and notes but saying it quickly and well is a lot harder than I thought it would be. That is why you have a radio talk show and I do not.

Peter Welch

Friday, December 19, 2008

Indecent FDA delays, Shades of Dr. Mengele

The issue of clinical trial access is far bigger than most Americans suspect. I will be on the Dr. Ken Kornhaus radio show tomorrow (Saturday) at 8am EST with Frank Burroughs of Abigail Alliance to discuss the phony promise of Compassionate Use under current FDA regs, the pointless bureaucratic delays of revolutionary new meds and therapies, and the increasing difficulty of getting into clinical trials due to inclusionary and exclusionary criteria that eliminate the sickest patients.

I urge all of you to listen to the show and call in with comments. You and your family may be in great health now but in a moment that can change. Once you get the “horror” diagnosis any extra time or finances you and your family have will likely be consumed. There will be precious little extra left to fight the FDA and big pharma. Get involved now. Look up Abigail Alliance and find out how.

There is a revolution in research going on in America right now. The medications and the therapies were undreamt up a decade ago. But this revolution is not getting to patients. The journey from lab bench discoveries to patient bedside therapies has become an ever lengthening process often taking decades. More awful still is that dozens of discoveries never get to patients because of the paperwork, time and especially cost of this process. These discoveries never advance. No one ever gets help. Something needs to be done. One start is a reform of the FDA clinical trial procedures to increase access and efficiency.

New research knowledge offers the possibility of the end of some of the most horrible chronic diseases in history of humanity. Researchers can manipulate cells inside the body with drugs like the PTC 124, so that slight errors in genetic instructions can be ignored by the cells gene reading machinery allowing the gene to function properly and the disease process to stop. There are meds called HDAC inhibitors which can turn on incorrectly turned off genes. Cancer in many patients is caused by p53 cancer suppressing gene being wrongly shut down. Turn on the p53 cancer suppressor with HDAC inhibitors or other similar drugs and the cancer melts away.

Read more about the denial of access to PTC124 in this article:

Other techniques allow immune cells to be manipulated inside the patients body with the result that "tolerance" cells can be exponentially increased. These “tolerance” cells normalize the immune system and turn off immune dysfunctions that cause various autoimmune disease and possibly even asthma and allergy. Or the immune cells can be “revved up” and targeted to kill particular cancers or infectious pathogens. All of this and far more is possible and it is being done today in labs and clinical trials. Far too many of us are dying while we wait for these advances.

New ways to kill resistant and increasingly virulent bacterial infections like MRSA, C diff, Iraqi bacter and others are held back from dying patients.

A father of three children at my wife's K-5 elementary school got a small cut on his hand on the job as a plumber. A resistant bacterial infection set in. Three days later he was dead! The brother of one of the teachers at the school was burned in a garage fire. He could have survived the burns, but he did not survive the infection. A perfectly healthy12 year old boy at a nearby middle school (Ramona) got the flu last winter ten days later he was dead from a bacterial pneumonia.

Three cases, three different doctors (at least), not one doctor asked for a compassionate use exemption for clinical trial antibiotics that might have saved all three lives.

Why? Not because they were lazy. No, because the compassionate use process is a dinosaur. It is incredibly time consuming and difficult even for emergencies. When doctors do try the companies invariably deny the request. NO is always the easy and safest answer. A “yes” might result in some unexpected outcome that would have to be reported to the FDA which could delay the already snail like pace of the FDA approval process even further. Each delay costs million maybe 100s of millions in lost sales and additional tests.

Recently an FDA approved cancer drug (Rituxan) showed remarkable efficacy in stopping Multiple Sclerosis. One of the researcher team members did not want the results shared. He said he was afraid too many MS patients would obtain Rituxan “off label” and there would not be enough MS patients available for his clinical trials to be completed. Shades of Josef Mengele! This researcher’s need for fame and compensation was far more important to him than the suffering of his fellow American citizens. We, the chronically ill, are more than clinical trial fodder. We are suffering human beings.

Worse, the FDA approval process is ever longer and ever slower. Fewer new drugs are approved each year. Bush budget cuts did not help. There are constant delays in the process. Bureaucratic black holes which shut down the approval process suddenly appear for who knows why? or for how long? It is always safer for FDA bureaucrats to say "no, let’s wait" then, "yes let’s go".

Clinical trials cost a billion dollars each and not just for each new drug, but worse for additional testing of existing FDA approved drugs for similar disease. For example Rheumatoid Arthritis (RA) drugs must be tested and FDA approved again before being used for Psoriatic Arthritis (PsA)—a nearly identical disease. Every PsA med was first tested for RA. There is not one RA drug tested on PsA patients that did not also work in PsA, yet PsA patients must wait years more for FDA approval while RA patients have the access to drugs.

PTC124 could save the lives of half of all the cystic fibrosis patients in Israel and up to 10% of cystic fibrosis patients in US. PTC 124 and similar meds have the potential to end any chronic disease that is caused by a tiny error in the DNA that causes the gene not to function. PTC 124 should work for some patients with autoimmune diseases and cancers. HDAC inhibitors hold the similar promise for a colossal range of chronic diseases.

Decency demands that these drugs be rushed to approval and allowed for every possible disease they might help.

Chinese medical tradition requires that the physician try to help the patient. Giving up is not an option. Western medical tradition says, “First do no harm.” Doing nothing may have been a good philosophy 3000 years ago when there was little knowledge and lots of bad out comes. Today it is a terrible philosophy. Doing nothing condemns thousands of Americans to death every year—that just those who die of out of control antibiotic resistant bacterial infections. Doing nothing is doing harm. How many more die of chronic conditions that could be helped and helped fast if the FDA clinical trial procedures were streamlined.

My son nearly died a year and a half ago of suffocation as his ribcage froze while a medication that could save his life and turn off his three related autoimmune diseases was denied to him. I could not get approval for Compassionate Use from the company even though phase II and III clinical trials results released months before my son’s near death were called "stunning" by outside observers. This medication that he was denied beat the most prescribed FDA approved med for his condition in head to head clinical trials. He was using that FDA approved medication and he was dying. How much worse could he get on a clinical trial med with such promise? Yet he was denied access.

In June of 2008 and FDA expert panel UNANIMOUSLY recommended approval of that medication. Wouldn't you expect the FDA to immediately approve it for marketing? No, of course not. As of today more than six months later, the FDA rhymes with DELAY still has not approved the medication. By the way, the name of that medication is Ustekinumab (CNTO 1275)—a FULLY human monoclonal that targets DIFFERENT immune inflammatory signals (IL12/23) than any other medication on the market. It is unique or would be if the FDA would stop stalling.

My son is still alive today only because another older and FAR more dangerous med has allowed enough reduction in inflammation for his ribcage to work again. Each six week infusion of this very dangerous medication made with NON-human mouse proteins is a spin of a medical Russian roulette. At any infusion his body could have a fatal adverse reaction to the FOREIGN mouse proteins.

What would you do if your child was dying and the medication that could save his life was locked up and denied to him? What value is human life in America today? What is more important antiquated FDA protocols or human life?

Wednesday, December 17, 2008

Type I Diabetes Celiac Disease same autoimmune genes

Following article again demonstrates that inflammatory autoimmune disease are genetically linked. If you have one you are at a much increased risk to develop another. The following are all inflammatory autoimmune diseases--RA, psoriasis, Ankylosing Spondylitis, psoriatic arthritis, diabetes type I, Crohn's, and likely many more of the eighty or so named diseases.

Some doctors who have not kept up with the literature do not realize that Celiac disease is an autoimmune disease. As this article and many others clearly indicate it is.

Today's posting is in memory of Barbara N who contracted type I diabetes at age 7 and who died just over ten years ago at age 42 after years of horrible complications.


Type 1 Diabetes And Celiac Disease Linked -

Scientists Identify Shared Genetic Markers
17 Dec 2008

Type 1 (juvenile) diabetes and celiac disease appear to share a common genetic origin, scientists at the University of Cambridge and Barts and The London School of Medicine and Dentistry, have confirmed. Their findings, which are reported in this week's edition of the New England Journal of Medicine, identified seven chromosome regions which are shared between the two diseases.

The research suggests that type 1 diabetes and celiac disease may be caused by common underlying mechanisms such as autoimmunity-related tissue damage and intolerance to dietary antigens (foreign substances which prompt an immune response).

Type 1 diabetes is an autoimmune disorder which causes the body to attack the beta cells of the pancreas, limiting its ability to produce the insulin necessary to regulate blood sugar levels. Celiac disease, also an autoimmune disorder, attacks the small intestine and is triggered by the consumption of gluten (a protein found in wheat, barley and rye) and cereals.

The development and anatomy of the small intestine and pancreas are closely related, and the gut immune system shares connections with pancreatic lymph nodes, which have been linked to an inflammation of the pancreas and the destruction of beta cells.

In order to assess the genetic similarities and differences between the two inflammatory disorders, the researchers obtained 9339 control samples, 8064 samples from people with type 1 diabetes and 2560 samples from individuals with celiac disease. They found a total of seven loci (regions of a chromosome) were shared between the two.

The researchers, who were funded by the Juvenile Diabetes Research Foundation, the Wellcome Trust and Coeliac UK, believe that these regions of the chromosomes regulate the mechanisms that cause the body's own immune system to attack both the beta cells in the pancreas and the small intestine.

Their results suggest that type 1 diabetes and celiac disease not only share genetic causes but could have similar environmental triggers as well.

Professor John Todd, from the University of Cambridge, said: "The next step is to understand how these susceptibility genes affect the immune system, and to keep exploring environmental factors that might alter the risk of type 1 diabetes, which results from an incredibly complex interaction between nature and nurture."

Professor David van Heel, from Barts and The London School of Medicine and Dentistry , said: "These findings suggest common mechanisms causing both coeliac and type 1 diabetes - we did not expect to see this very high degree of shared genetic risk factors." Richard A. Insel, MD., Executive Vice President, Research, at JDRF, said: "These studies demonstrate that type 1 diabetes and celiac disease share far greater genetic overlap than had been appreciated, which helps explain the high prevalence of both diseases occurring simultaneously in an individual, and provide new avenues for understanding the cause and mechanisms of both diseases." Sarah Sleet, Chief Executive of Coeliac UK said: "This is a real advancement in understanding the underlying mechanisms generating celiac disease, a much under diagnosed condition which affects 1 in 100 people in the UK today however, only 1 in 8 of those has currently been diagnosed. We hope that these findings will help in increased awareness and diagnostic understanding of both celiac disease and type 1 diabetes."

Type 1 diabetes and celiac disease together affect about 1% of the population.

About JDRFJDRF is a leader in setting the agenda for diabetes research worldwide, and is the largest charitable funder and advocate of type 1 research. The mission of JDRF is to find a cure for diabetes and its complications through the support of research. Type 1 diabetes is a disease which strikes children and adults suddenly and requires multiple injections of insulin daily or a continuous infusion of insulin through a pump. Insulin, however, is not a cure for diabetes, nor does it prevent its eventual and devastating complications which may include kidney failure, blindness, heart disease, stroke, and amputation. Since its founding in 1970 by parents of children with type 1 diabetes, JDRF has awarded more than $1.3 billion to diabetes research, including more than $156 million in FY2008. In FY2008 the Foundation funded more than 1,000 centers, grants and fellowships in 22 countries. JDRF
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Dr. Ken radio appearance FDA delays Ustekinumab

Ustekinumab is a monoclomal single injection medication that blocks two inflammatory immune signals that no other medication on the market targets. It has had stunning results in clinical trials of psoriais. It has beaten Enbrel in head to head trials. Centocor and others expect it have good efficacy in a wide range of inflammatory autoimmune diseases other than psoriasis including ankylosing sponkylitis, psoriatic arthritis, Crohn's and RA among many others. I posted the following about my appearance on the National Psoriasis Foundation Website under the CNTO 1275 thread:

I am scheduled to be on the Dr. Ken (Kronhaus) segment of the Doug Stephan Good Day radio program this Saturday, December 18 at 8:00 AM EST to talk about FDA delays in approving life changing and revolutionary medications, specifically CNTO 1275, Ustekinumab, Stellara. I urge you to google the Dr. Ken radio program, Good Day Health and listen on line. You can also call the show with your own stories.

People in our community are suffering needlessly for many extra years while we wait for the spectacular advances in research to make it through the snail like clinical trial and FDA approval process. Some of us are dying while we wait. When the “stunning” clinical trial results for Ustekinumab were revealed in the Spring of 2007, the FDA should have rushed approval of this novel, first in its class, medication. Instead they did nothing. When a new med has the potential to be a game changer and there is nothing else like it on the market, the medication should get some kind of expedited review by the FDA. Minimum!

My 26 year old son, Paul, has psoriasis, PsA and Ankylosing Spondylitis. Even with the maximum amount of Remicade for his body weight, he is in constant pain and frozen up. He compares himself to the tin man in the Wizard of Oz movie before Dorothy oiled him.

My son was a perfectly healthy 21 year old college senior when he developed a sore knee in the fall semester. He had no psoriasis at the time. The sore knee was the very first symptom of the autoimmune disease hell to follow. The ever more sobering diagnoses kept pace with his ever worsening physical deterioration. We desperately tried to stop the progression. Paul failed at Humira and Enbrel (although the Enbrel gave him about two months of good improvement before it stopped working). He had life threatening allergic reactions to sulfasalazine and methotrexate and was forced to stop using them.

In the summer of 2007 his ribcage had become so stiff that he literally could not breathe. Twice that summer my wife and I sat by his bedside watching him, comforting him, and expecting him to die. His rheumatologist at the time turned out to be incompetent. She could not diagnose the inflammation of his ribs, nor did she notice the AS symptoms, and told him he was not "trying" hard enough. Paul ended up taken to the hospital by ambulance where thankfully he received a proper diagnosis from an Emergency Room physician. Several shots of cortisone got his ribcage working again.

We now have a competent rheumatologist and Paul is on Remicade which has worked well enough to keep him breathing and give him a bit of improvement. But as you know Remicade is a chimeric monoclonal that is about 50% mouse protein. Paul's history of allergic reactions makes him a poor candidate for monoclonals made from non-human sources and a likely candidate for a life threatening adverse reaction. I want him off mousey monoclonals ASAP.

I desperately tried to get Ustekinumab (which is fully human) for my son during the early summer of 2007. I had contacts with top management at Centocor and still was not able to persuade them to apply to the FDA for a Compassionate Use exemption for Paul’s use of Ustekinumab. I was unsuccessful then and in the months since. Nor did Paul make it past the inclusionary and exclusionary criteria for a local clinical trial of ustekinumab later that summer (August 2007).

Every six weeks my son has a two hour infusion with Remicade. He must take pre-treatments with antihistamines and steroids before the infusion. He must have the Remicade infusions to breathe, yet every infusion is like playing medical Russian roulette. At any time he could have a serious (even fatal) life threatening reaction. The danger lasts for weeks after the infusion. His diagnosed allergies, asthma and adverse reactions to foods and other meds puts him at high risk of an adverse reaction. The more times he is exposed, the more likely a reaction is.

The FDA and Centocor are aware of mouse protein problems with the "old technology" monoclonals. Centocor has a new fully human version of Remicade in clinical trials. It is called CNTO 148 or golimumab. The FDA and the entire scientific community is aware of the benefits of TNF alpha inhibitors like Remicade, Enbrel and Humira. Knowing both the dangers of mousey monoclonals and the benefits of TNF alpha inhibitors in inflammatory conditions why wasn’t the fully human Remicade--Golimumab (CNTO 148) rushed to FDA approval for patients years ago? Even before Ustekinumab.

Other therapies for autoimmune disease offer incredible promise from vaccines to B cell depletion therapies, genetic and medicinal ex vivo and in vivo boosting of regulatory cells, to stem cell therapies. All of these are in various stages of clinical trials right now. All have had great success. Yet none are approved or even close to approval and not even months away from approval— decades away!

The first B cell depletion therapy was serendipitously discovered to benefit autoimmune disease when a B cell cancer victim who also had RA was given Rituxan. He was cured of both conditions. That was in 1987! It is now over twenty years later and Rituxan still is not FDA approved for 76 of the 80 autoimmune diseases that it likely would be effective for.

B cell depletion therapy with the "old technology" mousey monoclonal, Rituxan, offer weeks to years of disease remission. Newer B cell therapies that are FULLY HUMAN--HuMax CD2O and other monocloals targeting CD 22 receptors on the B cells offer the hope of better efficacy and fewer adverse reactions. The NIH should be funding these trials and the FDA should be pushing for approval in weeks or months NOT decades.

Prochymal a human stem cell product offers the possibility of life time remission. That’s right the real possibility of no more autoimmune disease for life. Imagine having regulatory immune cells living happily in your body and doing what regulatory cells are supposed to do--REGULATING the immune system.

Prochymal is made of the precursors of the complete immune system from many donors. Somehow it does not provoke graft versus host disease. In fact it actually cures GvH in bone marrow transplant patients. How? Who knows? Who cares as long as it works.

For about half of the diabetes type I patients who have gotten it in clinical trials, all their symptoms disappear. Crohn’s patients do even better. Two weeks after infusion the autoimmune disease condition is gone, done, finished, kaput!

My son could have the possibility of a fifty/fifty chance of his autoimmune disease being done and his life resumed by the next month if he could get Prochymal today. Nothing for sure. Danger? Yes. Risk? Yes. Worth it? Shouldn’t it be for him to decide? Why isn’t he given a chance to make that decision?

As the Denny Crane character said on Boston Legal when he was denied clinical trial medication for his Alzheimer’s that allowed a possibility of getting better, “I’d kill for a possibility.”

On Boston Legal in the series finale the Denny Crane character (William Shatner) was allowed by the Supreme Court to get the clinical trial drug but only him and no one else.

In reality our US Supreme Court has ruled that we have NO right to clinical trial drug. None. Not any right. No chance at all. Even if we will die with no hope of any other therapy. Too bad. No exceptions not even for rich lawyers like Denny Crane's character.Thee archaic FDA rules for NDAs and BLAs will require each and every of the eighty or so autoimmune diseases to be tested separately for Procymal. Nonsense! There is no good reason for separate testing.

Autoimmune disease runs in families. If you have one diagnosed autoimmune disease, you are likely to get another. Inflammatory autoimmune disease genes have been found to be similar in all inflammatory autoimmune disease conditions.

New therapies should be tested on MOST of the 80 autoimmune diseases at the same time. How long before psoriasis patients have access to Prochymal? Thirty years of FDA delay? While one autoimmune disease at a time goes through clinical trials at a cost of a billion dollars for each trial, we die! Bernie Mac (autoimmune lung condition), Christopher Reeve (mastocytosis), Richard Pryor (MS) and so many others and one day in the summer of 1987 almost my son.

When will the FDA figure out that the new genetic discoveries in autoimmune disease indicate that new therapies should be tried on all autoimmune conditions at once, not on one at a time. They are NOT different disease processes. They merely have different names based on an archaic naming system that named diseases for the organs or areas of the body they manifest in. The old idea before genetics was one organ, one disease, one medical specialty. Did you ever wonder why we have to decide between a dermatologist and a rheumatologist? Why is an MS patient sent to a neurologist? It’s nuts. These are all autoimmune disease. There should be ONE autoimmune specialist for all of us. There should be one set of tests for new drugs for all of us. The FDA’s clinical testing rules should reflect the new discoveries in the field.

If you are bothered by the FDA ever slowing process of new drug approval and would like to be heard on a nationally syndicated show, I urge you to call in this Saturday morning to the Dr. Ken show.

Thursday, December 11, 2008

Gene therapy lessens inflammatory autoimmune disease

University of Michigan school of dentistry discovered a gene therapy that lessens peritonitis. This gene therapy for peritonitis helps to stop autoimmune disease as well!

Excessive amounts of TNF alpha, an immune system signalling molecule, is linked not only to all inflammatory autoimmune disease, increased risk of cancer and heart disease but increased risk of infections.

According to the article below RA patients (likely all inflammatory autoimmune sufferers) have a four time higher risk of peritonitis than people without autoimmune disease.

U of Mich Ann Arbor has come up with an injection of an inactivated virus containing a gene for TNF alpha receptors. These receptors act as sponges to soak up excess TNF alpha.

Apparently we in the autoimmune community lack enough of these receptors. I personally suffer from frequent bacterial infections of the skin, peritonitis of the gums, and bouts of pnuemonia (as well as four skin cancer episodes with three kinds of skin cancer).

The dentists at U of Michigan were just trying to reduce peritonitis a bacteria driven disease of the gums that results in bleeding gums, then receding gums and eventually loss of teeth. Their gene therapy worked perfectly to reduce TNF alpha which reduced inflammation of the gums which reduced the bacteria's ability to infect.

However, a serendipitous side effect of treatment was that in RA patients their RA symptoms were substantially reduced as well. Apparently a high percentage of the patients they tried the gene therapy on had RA. No surprise when researching peritonitis.

The gene therapy treatment apparently consisted of a single shot in the arm. For RA patients a 30% reduction in symptoms. I would take a single shot for a 1% chance.

The improvement in RA patients should come as no surprise because the most effective meds for inflammatory autoimmune disease today soak up TNFalpha. Those meds are Enbrel, Humira, Remicade, and Cimzia.

This research is good news for us looking toward better therapies in the next two but offers no hope now unless maybe you have enough money to buy an endowment at U of Mich Ann Arbor which might get you access OR call you congressional Reps and US senators and ask them to support Abigail Alliance's FULL ACCESS to experimental medication and therapies.

University of Michigan
Gene therapy effective treatment against gum disease
ANN ARBOR, Mich.---Scientists at the University of Michigan have shown that gene therapy can be used to successfully stop the development of periodontal disease, the leading cause of tooth loss in adults.
The findings will be published online Dec 11 in advance of print publication in Gene Therapy.
Using gene transfer to treat life threatening conditions is not new, but the U-M group is the first known to use the gene delivery approach to show potential in treating chronic conditions such as periodontal disease, said William Giannobile, professor at the U-M School of Dentistry and principal investigator on the study.
"Gene therapy has not been used in non-life threatening disease. (Periodontal disease) is more disabling than life threatening," said Giannobile, who also directs the Michigan Center for Oral Health Research and has an appointment in the U-M College of Engineering. "This is so important because the next wave of improving medical therapeutics goes beyond saving life, and moves forward to improving the quality of life."
The preclinical study offers was a collaboration with the Seattle-based biotechnology company Targeted Genetics. In July, Targeted Genetics released human trial results that showed the same gene therapy approach used to stop periodontal disease had positive affects in human patients with rheumatoid arthritis, another chronic, non-life threatening, disabling condition. The company tested 127 human subjects and showed a 30 percent improvement in pain relief, and gain of function, among other enhancements using the gene treatment.
People with rheumatoid arthritis are four times more likely to also be afflicted with periodontitis. Periodontal disease is also linked to systemic conditions such as heart disease, bacterial pneumonia and stroke, likely due to the spread of bacteria coming from the oral cavity that invade other parts of the body.
Using gene therapy, Giannobile's group found a way to help certain cells using an inactivated virus to produce more of a naturally-produced molecule soluble TNF receptor. This factor is under-produced in patients with periodontitis. The molecule delivered by gene therapy works like a sponge to sop up excessive levels of tumor necrosis factor, a molecule known to worsen inflammatory bone destruction in patients afflicted with rheumatoid arthritis, joint deterioration and periodontitis.
The gene also delivers quite a bit of genetic bang for the buck. The periodontal tissues were spared from destruction by more than 60-80 percent with the use of gene therapy.
"If you deliver the gene into the target cells once, it keeps producing in the cells for a very long period of time or potentially for the life of the patient," Giannobile said. "This therapy is basically a single administration, but it could have potentially life-long treatment effects in patients who are at risk for severe disease activity."
The next step is additional safety testing on periodontal patients, he said.
The research was funded by the National Institutes of Health. Co-authors included Haim Burstein, a research scientist at Targeted Genetics Corporation, and members of U-M research team Joni Cirelli, Chan Ho Park, Jim Sugai and Katie MacKool.
For more on Giannobile, visit:
U-M Dentistry:

Tuesday, December 9, 2008

AUTOIMMUNE CURES IN DANGER!! Biotechs running out of money

Our cures are almost here but the financial crisis may bankrupt nearly half of biotech in America. See the article below taken from the New York Times this morning. Call your Congressional Representatives and Senators and ask them to support this tax law change.

December 10, 2008
Biotech Industry Seeks Help via Change in Tax Law

Move over Big Three. Little Biotech is joining you in seeking federal assistance.
Biotechnology industry executives plan to visit Congress on Wednesday to ask for a temporary change in the tax law that would let money-losing companies get cash from the government now, in exchange for tax credits they would pledge not to take if they eventually become profitable.
The change, if Washington approved of it, could enable the industry to receive potentially hundreds of millions or even billions of dollars, on the condition that the money would be used for research and development.

The effort comes as many smaller biotechnology companies, particularly those trying to develop drugs, are facing a severe cash shortage that is forcing them to dismiss workers, curtail research and even file for bankruptcy protection or liquidation.

Prospects for the proposal are unclear.

But Allyson Y. Schwartz, a Democratic member of the House Ways and Means Committee, which handles tax matters, said she would push to include the proposal in the forthcoming economic stimulus package and expected many of her colleagues to view it favorably.
“Innovation and technology are growth areas for American businesses and American workers and should be part of this package,” said Ms. Schwartz, whose district in the Philadelphia area is home to some pharmaceutical and biotechnology offices.

A spokeswoman for President-elect Barack Obama said his transition team was not commenting on individual provisions of the stimulus package beyond what has been revealed publicly.
The big profitable biotech companies like Amgen and Genentech remain financially sound. But of the 370 publicly traded American biotechnology companies, the number with less than six months cash on hand is approximately 125 — nearly double the total last year, according to the Biotechnology Industry Organization, a trade group. Developing a drug can require hundreds of millions of dollars and 10 years or more, so even in good economic times some small companies struggle to raise money.

But with financial markets in turmoil, investors have become reluctant or unable to provide the infusions of cash, pushing many biotech companies to the brink.

In seeking assistance, the industry is quick to distinguish itself from the automakers, banks and other supplicants in Washington, portraying itself as a model of innovation and American competitiveness.

“This is not a question of our companies operating with what some perceive as a flawed business model,” said Alan F. Eisenberg, an executive vice president of the Biotechnology Industry Organization, which is known as BIO. “This is about our companies taking a decade to get a product on the market, and during that time they need to have investor capital, and that capital is not available.”

The industry’s idea is to let companies turn their very weakness — their huge losses — into an asset. Under current law, net operating losses can eventually be used to offset some taxes once a company is profitable. But that does little good for companies struggling with losses and a lack of cash now.

So the industry’s proposal would let companies receive payments from the government now in exchange for giving up those tax deductions later. The industry would agree to a cap, perhaps $30 million, on the amount any single company could receive.

Mr. Eisenberg of BIO said the proposed change would be in effect only for a year and would apply to companies outside of biotechnology as well. Few other industries, though, require as much time and money to develop a product as the biotechnology industry.

Biotechnology might not seem an obvious candidate for a bailout. The industry employs only about 200,000 people in the United States, according to the accounting firm Ernst & Young; the automobile industry employs millions.

“Research-based companies that employ 30 people don’t necessarily stimulate the economy,” said a Washington lobbyist for a large pharmaceutical company, who was skeptical the proposal would win backing.

This person, who spoke on the condition of anonymity because he was not authorized to talk to the media, said the proposal’s opponents could argue that assistance was not needed because a company with a truly promising product would be able to sell the rights to that product, or the entire company, to a larger drug company.

The biotechnology industry is also notoriously risky, with many companies never achieving profitability despite spending hundreds of millions of dollars. The chief executive of Genentech has estimated the industry as a whole has lost about $100 billion since the field’s inception in 1970s. Even as of last year, the American biotechnology industry as a whole was not profitable, although it was getting close, according to Ernst & Young.

The biotechnology industry will argue that it is responsible for creating a large number of drugs now being tested that will be needed by an aging population in the future. And it will argue that it is a bastion of American competitiveness.

“It’s one of the few places where the U.S. is the undisputed leader of the world,” said Alexis Borisy, the chief executive of CombinatoRx, a biotech company in Cambridge, Mass., that recently cut 80 employees, or two-thirds of its work force, to conserve its cash after two drugs did not perform well in clinical trials. “Do we allow that to be cannibalized?”

The industry has paved the way in developing ways to treat rheumatoid arthritis and multiple sclerosis as well as cancer drugs like Genentech’s Avastin, ImClone’s Erbitux and Celgene’s Revlimid. OSI Pharmaceuticals, which developed the lung cancer drug Tarceva, lost a cumulative $1.3 billion from its inception in 1983 through 2006 before finally breaking into the black.

Since many companies will never reach profitability, the industry acknowledges that an upfront cash payment would have to be significantly less than the value of the deductions.
For instance, Mr. Eisenberg said, a company with $100 million in net operating losses would be entitled to about $35 million in lower federal taxes when it eventually became profitable. So perhaps the company could be paid about $20 million now, he said.

Ustekinumab, Prochymal, and Good Samaritan Pharma companies

The following is a copy of part of an email I sent to a fellow autoimmune suffer. He has psoriasis like my son but not PsA or AS. I thought the email summed up a bunch of problems we in the chronically ill community suffer from. I decided to share part of the email with this blog audience. I ADDED SUBTITLES TO THE LETTER FOR THIS POST.


No, Paul has not yet had the opportunity to try Ustekinumab despite my best attempts to get it for him. We almost got him into a clinical trial to test Usetkinumab on PsA but his psoriatic lesions were not large enough. It did not matter how bad and disabling his PsA was.

It’s sad that there are not better ways to measure the systemic effects of PsA then to physically look at the skin and joints. Wouldn’t it be nice if there were blood tests looking at gene expression to determine the status of the disease instead of subjective quality of life measurements and size of lesions?


I also think it is absolutely unconscionable that a medication with such promise as Ustekinumab can be denied to people in need for so long. The FDA approval process is way too slow and based on archaic disease classification criteria. If Ustekinumab is FDA approved this month for use, it will only be approved for psoriasis. Yet its mechanism of action very likely would be of benefit for related inflammatory autoimmune diseases as well.

It should certainly work for PsA and ankylosing spondylitis. Every medication that helps PsA started as an RA medicine so shouldn’t CNTO 1275 be very likely to be useful for RA as well as PsA? I would think that diabetes type I and even MS might be helped. Too bad the FDA requires separate billion dollar clinical trials for each condition rather than allowing for the testing of many related conditions at once.


As to the Cimizia and Paul, no we have not tried it. Because of Paul’s history of hives angioedema and breathing problems with medications and foods, a “humanized” monoclonal like Cimzia is not my first choice. Humanized monoclonal are up to ten percent mouse protein. Right now Paul is taking Remicade a chimeric monoclonal that is up to fifty percent mouse. Each infusion is scary like spinning the cylinder on a revolver in Russian roulette.

He and all other patients who are infused with Remicade must take massive doses of steroids and antihistamines before the Remicade to try to prevent reactions. Even so many patients especially those like Paul develop severe adverse reactions after a few to few dozen infusions.

Cimzia is not FDA approved for psoriasis, is it? I know it has been in clinical trials for psoriasis. I have not heard of it being approved for psoriasis yet only Crohn’s. So we would have to use it off label. Just googled it. Supposed to be less likely to cause reactions—less immunogenicity—don’t you love research talk? Hmmm. Maybe it would be worth looking into.


Except we have had difficulty getting physicians to use medication “off label” even when clinical trials indicate it might be helpful. We have tried for years to get Rituxan* for Paul—no luck so far. We even tried to get him into a clinical trial for Rituxan with no success. Also my wife’s medical insurance refuses to cover off label use which if we could find a doctor to prescribe Cimzia, it would be an off label prescription. We would have to pay all of it out of pocket.

For Rituxan the cost of a complete course of treatment would be less then $10,000. Expensive but doable if we found a doctor willing. Cimzia, once a month subcutaneous, would cost what? $600 to $1000 I would guess based on what Enbrel and Humira cost. That would be in the $10,000 a year ball park. Same price. Still where could we find a doctor who would be willing to prescribe “off label” and risk his “career investment” as a physician?


We are spending around $2000 out of pocket every six weeks for Remicade infusions, currently—close to $18,000 a year. Maybe Cimzia would be worth asking about if Ustekinumab is not approved this month.


Certainly TNF alpha inhibitors like Cimzia help Paul. They keep his chest flexible enough to allow him to breathe. When the Remicade starts to wear off he starts to have more difficulty breathing—not as bad yet as the two suffocating episodes in summer of 2007 when the Enbrel stopped working. (Paul says he feels like the Tin Man in the Wizard of Oz before Dorothy oiled the rusty joints in the week or so before he gets the next Remicade infusion as the benefits of the previous infusion wear off)

Thanks for the Cimzia idea. Being FDA approved and on the market it has to be easier to access than Ustekinumab has been.


My long term goal is to find some way to get fully function regulatory immune cells working in Paul’s body (and mine too.) The closest to that happening that I can find are the clinical trials using Prochymal from Osiris.


Prochyma is a mixture of blood and immune forming cells from a lot of donors. It has had tremendous success in Graft versus Host Disease, Crohn’s and now diabetes type I.

Somehow getting these pre-immune and blood cells from lots and lots of donors overcomes the problem of the new immune cells attacking and destroying the recipients tissues (graft versus host) which has been one of the main problem with using bone marrow transplants as a way to cure autoimmune disease.


The drawback of Prochymal is that the infused cells cannot be tracked or eliminated once transfused and they can stay alive for decades even for entire life of the recipient. If something goes wrong, it stays wrong.


Yet if Paul and I had free access to any experimental drug or therapy, I would grab Prochymal in a minute. I have read anecdotal stories of Crohn’s patients, with decades long disease who two weeks after having the infusion of Prochymal had no sign of Crohn’s in their bodies. Endoscopes of intestines were completely normal. Patients had complete relief from their disease for first time in their lives. If Paul had an infusion of Prochymal today, he could be running around and playing ping pong with me by Christmas. If I got it, I could go back to work in January. Just the possibility of that cure fills me with hope. I do not think it is false hope. The only thing separating Paul and I from living normal lives is properly functioning immune cells—the kind that normalize out of control immune reactions.


That hope is why I am going on the radio show. I want patients to have better access to clinical trial drugs.


If I were a well placed Washington insider, I would advocate for the FDA to create a special classification for severely incapacitated or those in imminent danger of death as “accident victims,” then allow pharma companies to treat those patients without any danger of liability under some kind of “Good Samaritan” type umbrella of protection from legal liabilities and negative drug approval process consequences.


With such a classification people like my son and I could have access to any experimental medication that might help. The Pharma companies would be able to test new drugs and therapies on a wide variety of human diseases without fear that a failure would doom approval of their medication. In fact they may serendipitously discover that their drug is even better for a related condition, then for the one they were going to clinical trials with.


Besides relieving the pharma companies of any worries of negative consequences if they allowed expanded compassionate use for “accident victims”, the willing companies the “Good Samaritans” should also be able to get all positive results on “accident victim” patients as officially approved FDA data to be used in the FDA approval process of their new drug. I bet pharma companies would jump at the chance for more humans with more conditions being tested especially if there was a chance that they could get their new drug to market faster with positive data they could get fast and cheap.


With so many really amazing new therapies and drugs being developed, there is a huge need to get the research advances from lab bench to bed side quicker.


Paul and I would volunteer to be the “accident victims” in a heartbeat. Actually I would see us more like heroes or explorers willing to go out into the unknown at risk to ourselves to pave the way for better treatments for others.

I wonder if I can say all that in a ten minute segment on the radio?

Sorry to be long winded. I am so excited by the progress being made in the research community. Autoimmune disease is a fixable problem and the fix is at hand.


I asked for two hours segment and was offered ten minutes—better than nothing. I also asked if Frank Burroughs of Abigail Alliance can be included to talk about his Full Access legislation in the House and Senate. I hope to be on the radio show this weekend or next.

Hope all is well with you and your family.

Let’s make our generation the last one that ever has to suffer with autoimmune disease.

Father of Paul


*You probably know that Rituxan depletes B cells. A few “maladapted” B cell clones are responsible for AUTO-antibodies. Rituxan gets rid of all B cells including both the good ones (that make antibodies to childhood illnesses, etc.) and the “bad” AUTO-antibody producing ones.

Once the “bad” B cells are destroyed there are no AUTO-antibodies produced and the autoimmune disease goes into remission for weeks or even years.


Down side risk of Rituxan is the chance of life ending infections picked up in the environment after B cell depletion or from existing hidden and suppressed but not dead viruses in the patient’s body.

PML is the worst of the lot that include various herpes viruses. PML is a potentially lethal brain virus that is hidden and suppressed in a large part of the American population. Perhaps one in 2000 patients who take Rituxan will die from PML. So Rituxan is also Russian roulette, but with the hope of a long term remission of the disease.

Even with the chance of death Paul would take Rituxan if he could. So far no doctor in our area will prescribe it for Paul. It is “off label” for PsA.

Oregon University drug blocks 19 cytokines!

Oregon Health and Science University announced today that they have created a drug which normalizes the production of 19 inflammatory cytokines (immune system signaling molecules).

The best medicines on the market today only target ONE inflammatory cytokine. Remicade, Humira, Enbrel, Cimzia target the cytokine, TNF alpha. There are other meds that target IL-1 or IL-6. Soon there will be two new drugs that target TWO inflammatory Cytokines IL-12 and IL-23 (CNTO 1275 from Centocor, Abbots 875. But there is no drug any where in development today that blocks more than two inflammatory cytokines. This one at Oregon blocks NINETEEN!

I want it. I want it now! How do I get it for my son? or myself? money? mob influence? political organizing. The last one is the only one available to me. So I am going with it. Support Abigail Alliance. Support FULL ACCESS to clinical trial drugs! Call your Congressional Representative and US Senators!

Until we force the issue politically drugs like this are decades away from helping any of us or our loved ones. Under current FDA procedures and protocols the drug will be tested for cancer patients first. Probably it will take a year or two of successful clinical trials for cancer before it will be tested for autoimmune disease. No hope under existing testing and clinical trial protocols and regulations for FDA approval in less than ten years for our autoimmune conditions.

Read the original article here:

This new drug holds great promise as a treatment for all inflammatory autoimmune disease which includes RA, PsA, Diabetes Type I, psoriasis and most of the other 80 or so named diseases. The only one I am not sure it could help is Lupus, SLE because the latest research I have read indicates Lupus to have a cause with faulty disposal of damaged DNA fragments.

Too bad we can not have access. If you do not like waiting and suffering for a decade or moreafter major drug discoveries like this one, go to Abigail Alliance site and contribute and or call your local Congressional Office and US Senators offices and ask them to support the Abigail Alliance Full Access bill.

Monday, December 8, 2008

Clinical trials problems listed in radio show email

I cannot give out names or details but here is my email confirming my interest in doing the radio show. It contains the main points and problems in getting access to new medications and drugs.

Dear Dr. TTTT:

Yes, I would be quite willing to be on your program. The lack of access to
clinical trials is a problem that should be highlighted for the American public.
I talked to both my son and wife. They agree it is a good idea. My son gave me
permission to talk about his disability on air.

How long a segment would you be planning? I could go two hours or more on
various aspects of this issue.* Here are the five parts to the problem of Lack
of Patient Access to Breakthrough Clinical Trial Medications and/or procedures
that may be of interest to your audience:
(1) The politics of the problem
(2) Personal horror stories re my son condition and limitations highlighting the
desperate horror of the situation quality of life issues with ghastly risk of
death always lurking in background as result of the disease or current
inadequate full of side effects medication.
(3) Horror stories of others I know (relatives and close friends) with deadly
conditions bacterial infections, multiple Myeloma, Alzheimer’s, Multiple
(4) The difficulty in accessing clinical trials medication—either for
compassionate use or qualifying for a trial (Two Paul stories one regarding CNTO
1275 Ustekinumab—compassionate use and the other Rituxan—clinical trial where
his lesions were too small.
(5) The terrible frustration that cures are available but just out of reach and
the almost fiendish institutional cruelty that allows informed patients and
their loved ones to know of amazing breakthroughs without being able to avail
themselves of them.

Frank Burroughs of Abigail Alliance is very well connected. He will
definitely want to help. He might even be a good guest on your show. Certainly
he will want to give me impute as to his progress in Washington trying to change
the law regarding rights of patients to clinical trials. His Right to Life
Supreme Court challenge failed last January. The court refused to hear it.

Boston Legal, the TV program with William Shatner starring as a senior partner
(Denny Crane) in the law firm with early stage Alzheimer’s is currently doing a
two part show based in part on the Supreme Court’s refusal to hear Frank
Burroughs challenge to the FDA rules for clinical trials and lack of patient’s

In the Boston Legal version the Denny Crane character is trying to get access to
an experimental Alzheimer’s drug. He has gotten the Supreme Court to hear his
case and he will argue it in this week’s episode. I mention the show as it might
be useful as the set up to use to introduce me and my son’s problem.

Right now Frank Burroughs is pushing another piece of legislation in Congress to
give the sickest and most desperate patients access to phase II and III
medications. These are the patients who under current practices have the LEAST
access to the meds. The really sick patients fail at making it past the
exclusion criteria of the clinical trials protocol.

Frank would be an interesting guest as well although he and I have very
different political views (He’s conservative. I am more liberal) and moral views
regarding embryonic stem cell research. Any research that helps my son I am for.
He is a staunch Roman Catholic and has a different perspective. Still we are in
agreement on the need to change the law and FDA proctocols and procedures
regarding clinical trials.

A third person who would have contacts with the FDA is XXXX MD FACC
Senior Director, SSSS GGGG at (Big Pharma company name withheld). I have corresponded with him by email after Frank Burroughs set up the contact. I am not sure that he would
want (Big pharma company) name mentioned, but he is a good man. He might give us an FDA
contact person as well.

He might also want some input as to what I say. I do not want to embarrass him
or (Big Pharma company). His company is playing by the rules as they exist now. They have no

Dr.XXXX might also have some ideas about how he would like the clinical
trials rules changed so drugs can get to market sooner. (Big Pharma company) could save a
billion dollars for each clinical trial, it does not have to do with some FDA rule

The CNTO 1275, Ustekinumab, could have very wide applications for many, many
other of the eighty autoimmune diseases in addition to psoriasis that it has
been tested on is under FDA review for approval to treat.

Eighty billion on eighty clinical trials for eighty autoimmune conditions over
thirty years is lot of money and time to spend on unnecessary duplicative
clinical trials. If (Big Pharma company) could test all autoimmune diseases at once in one
trial instead of eighty, a lot of (big pharma company) capital could be conserved. I would
think Big Pharma like (this particular big pharma company) would be eager for changes and someone like Dr. XXXX might want to add to your program at least indirectly.

Let me know when you might want me on and the direction you would like to take
the show.

Thank you so much for your response and interest in this problem.