Wednesday, December 17, 2008

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.

2 comments:

Anonymous said...

Drug trials are almost always sponsored and paid for by pharmaceutical companies. It is the drug companies decision regarding which autoimmune indications they want to test their new drugs for first. this is often limited by $$$, since as you know clinical trials are expensive. I don't disagree that the FDA could be more efficient (and perhaps rules could be changed), but you are inaccurate and incompletely informed to lay all the blame with FDA. While some autoimmune diseases do often occur together, it is also an exaggeration to think that all immune modulatory drugs will benefit all autoimmune diseases. Also, it is not good to mess with all cytokines. Cytokines provide important functions in the body. So, while your frustration and concern are understandable, your solutions are somewhat overstated.

the_breeze said...

Dear Concerned Dad,
I have read your post here and also what you wrote on the Nat P message boards. I really feel for you and your son. It must be tough knowing there could be a cure and not be able to get it. I agree with everything you have mentioned and I hope to get through to Dr.Kens show this Saturday. I am also have plaque P and Psa. I was sick back in 1976 with Hep B and probably had Hep C then but it was not known of at the time. In 2003 I moved to FL and was diagnosed with Hep C by a Rheum and told I could not go on biologics until I took care of it. So I did. I took the awful medicine for a year and got the viral count down low but not gone. They then let me take Enbrel and I was on it for 3 yrs. It stopped working for me however and now I am on Remicade every 4wks.@900mg. It is not working either. I also am waiting on Stelara. I would be happy to call the show and discuss it with you and Dr. Ken.

You can email me at gandy55@gmail.com
Thanks Richard