Thursday, May 10, 2007

Blocking Immune Signals gives "Stunning Results"!!

More good news on autoimmune treatments—new treatments in phase III testing are expected to revolutionize treatment strategies for autoimmune disease. and
These new treatments are not cures or virtual cures but they are better than anything we now have. They should make as big an impact on autoimmune disease as the introduction of TNF-alpha inhibitors—Enbrel, Humira and Remicade.

These new biologics are fully human monoclonals that block two immune system chemical signals called interleukin 12 and 23. The experimental results have been so good that the two companies involved are racing to get this product through clinical trials and to market. Whoever wins is going to make a fortune. Even the runner-up should get rich with the leftovers. For stock speculators, the companies are Abbott and Centocor (Johnson and Johnson).

Right now the companies are both using plaque psoriasis autoimmune patients in clinical trials. The “wow!” factor of showing before and after pictures of patients with cleared plaque patches has won out over the lure of more patients and more potential customers that the Big Four (RA, SLE, MS, and Type 1 diabetes) have in their favor.

This is great news for my son and others with psoriasis, not so good for the rest of you. However, now that Big Pharma has figured out that a treatment for one autoimmune disease is a potential treatment for all autoimmune disease, I feel confident that this new monoclonal will be quickly tested on other autoimmune diseases.* Johnson and Johnson’s division, Centocor made too much money qualifying Remicade for just about everything while Abbott and Amgen sat on the sidelines. Abbott will not let that happen again.

This treatment while potentially revolutionary will not be the final cure we are looking for. It does block the inflammatory process farther upsteam than TNF-alpha inhibitors. This is good news. The closer to the beginning of the initiator of the autoimmune cascade, the more likely the biologic will be to have greater efficacy and fewer side effects. However, what we all want is to shut down the cascade completely. These new biologics will not do that. The cascade will still be constantly trying to re-start. These medications to block IL-12 and 23 will needed to be taken for the long term. Once they are stopped, the autoimmune disease will return.

Better still than blocking Il-12 and IL-23 will be blocking or disabling “autoimmune, antibody producing” B cells. (See my blog entry: B Cells keep the autoimmune pot boiling) There are new medications which will do that coming down the road in the next two or three years. These medications will need to be taken once a month to once every six months. They will have significant danger of infection and cancer and will not be a permanent cure. The first of these to be FDA approved for use in autoimmune disease was Rituxan. It is quite dangerous. There are better and less dangerous ones just around the corner—possibly FDA approved by about 2010. But they will not be a cure.

What we want is a permanent cure--something that turns off the cascade completely. Mice have these type of cures. We could too if we are willing to agitate and yell loud enough. Those full blown human cures to come will be with vaccines, fetal stem cells, or gene therapy manipulation of our own bone marrow. All three techniques have been successful at curing mice with autoimmune disease. Wouldn't it be nice to be cured? Wouldn't you like to be normal again? You could be if you are willing to yell as loud as AIDS patients did in the eighties.

What will you do today to get those cures to clinical trials?

*IL-23: a master regulator in Crohn disease - Nature Medicine
Indeed, several recent studies knocking out IL-12 and IL-23 subunits in animal models of inflammatory diseases such as multiple sclerosis and rheumatoid

Cytos Responds!

I wrote to Cytos some time ago to ask about progress on their anti-TNF-alpha vaccine (TNFQb). The Cytos Director of Corporate Communications wrote back the next day with an update. I have posted her email below.

She says in the email that we can expect results from their latest clinical trials to be published between now and the end of June. I hope all goes well. Imagine having your own body produce the anti-TNF-alpha antibody. It would be so much safer, easier and cheaper.

Right now the cost of our son's Enbrel is $3000US a month. Lucky for us, my wife has family medical insurance through her work. Without her insurance we would not be able to afford the medicine. Her insurance covers only part of the costs of his medicine and physcian appointments. We still pay several thousand dollars a year for those costs. But without her insurance, our costs would approach forty thousand dollars a year. We would be bankrupt in a year or two.

Here in the US, if you cannot work at a place with family medical coverage, you cannot afford most medications. We do not have universal health care like the rest of the industrialized world. Very sad.

It takes a lot of money to buy TV ads in US. The candidate with the most TV ads almost always wins. Only major corporations have enough money to donate to politicians to pay for those ads.

Big Pharma is the biggest corporate donor, followed by Big Oil and major insurance companies.

Politicians who want to be re-elected must pass the legislation that Big Pharma and other big corporations want. Therefore no control on drug price. No universal health care that would put insurance companies out of business. Regulatory agencies that were created to protect ordinary citizens are now all run by mangers and lobbyists on loan from major corporations.

The Cytos email follows:

Dear Mr. Welch,

many thanks for your e-mail and your interest in our vaccine TNFQb. I have summarized below the current status for this vaccine candidate for your information. I hope this is helpful. I will also put your address on file, if this is fine with you, so you will be getting the news on this product candidate in future.

In October 2004, Cytos initiated a combined phase I/IIa clinical trial with TNFQb. The randomized, double-blind and placebo controlled study includes 48 patients with moderate to severe plaque psoriasis and is designed to evaluate the safety, tolerability and exploratory efficacy of the vaccine. Three different dose regimens have been already tested in a first part of this study. Initial clinical observations obtained in December 2005 suggested that the vaccine candidate is safe and generally well tolerated. Furthermore, it was observed that the number of patients who mounted an anti-TNF-α-specific antibody response was identical to the number of patients scheduled to receive TNFQb (study still blinded). The antibody levels were found to decline over time in all these individuals. This is an important safety feature for an Immunodrug™ targeting a self-molecule.

In 2006, the second part of this phase I/IIa study was performed with 24 patients. The highest previously tested and well tolerated vaccine dose (i.e. 300 μg) was compared with placebo. The patients in this second part of the study have completed the treatment period and data management is currently in progress. Throughout the treatment period, no safety concerns were raised and all vaccine injections were performed as planned. The first phase I/IIa study results are expected in this second quarter 2007.

I am sorry that I can not give you more detailed results right now and I wish you and your family all the best.
With best regards,
(name withheld)
Director Corporate Communications
Cytos Biotechnology

Tuesday, May 1, 2007

Autoimmune Vaccine-Cytos Biotechnology

Cytos Biotechnology, a Swiss, company, is developing a number of vaccines that if successful could revolutionized the treatment of autoimmune disease, tobacco addiction, excess weight problems (metabolic disorder-type 2 diabetes), allergy, asthma, and eczema.

The autoimmune vaccine is meant to cause our bodies to produce our own antibodies to TNF-alpha. Instead of paying $1000-3000US a month to buy mouse and hamster antibodies o TNF alpha, we would make our own!

TNF-alpha is the chief immune system messenger causing inflammation. It is the main target of the biologics for various autoimmune arthritis diseases. The vaccine, if it works, will be useful for any autoimmune patient who takes Remicade, Humira, or Enbrel.

Cytos picked plaque psoriasis, probably because of the ease of visually assessing progress should the vaccine work. Pictures sell product. But just because Cytos started with plaque psoriasis does not mean the vaccine wouldn't help many (most) other autoimmune conditions.

Remicade is a mouse antibody that attacks TNF-alpha when injected into us. Humira is a fully human antibody that also attacks TNF-alpha. Enbrel is a Chinese hamster ovary fusion protein whose target is again, TNF-alpha.

The problem with each of these is that over time our body's own immune system starts to make antibodies against these medicines destroying them before they can destroy the TNF-alpha. The longer we take these biologics the less likely they are to work. Worse yet, for the ten percent of us who get hypersensitivity reactions, the longer we inject any foreign antibodies or proteins, the more likely we are to have a life threatening reaction.

The Cytos vaccine gets around this problem by stimulating our own immune systems to destroy TNF-alpha with our own antibodies. Good idea.

Now the bad news, clinical trial results for phase II use of this anti-TNF-alpha vaccine were supposed to be announced last fall. A quick Google search finds no mention of these results being announced. Why? Did it take longer to register clinical trial subjects than anticipated, thus delaying the start of the trials? Did the vaccine fail to work? or Did it work too well?

If it worked too well volunteers may have had too high a rate of infections and cancers. TNF-alpha is crucial for the prevention of both. So while reducing the amount of TNF-alpha is a good idea, getting rid of all of it is not so good. Who knows what caused the delay? I have emailed Cytos to ask them these questions. We will have to wait for Cytos to reply. In the meantime, read more below.

Here is a summary of how the vaccine is supposed to work. It is from the Cytos website. Here is the URL:
Then skip down to the following:
"View information about the vaccine CYT007-TNFQb to treat psoriasis."
Click on this button: TNFQb Facts English or read part of the article below.

Proposed Mode of Action
CYT007-TNFQb is a therapeutic vaccine designed to instruct the patient's immune system to produce a specific anti-TNF-α antibody response that is able to neutralize the action of TNF-α.

This should prevent the binding of TNF-α to its receptors TNF receptor I or TNF receptor II, which are expressed by many different cell types, and reduce the subsequent inflammatory response.

In contrast to TNF-α inhibitors based on recombinant proteins and monoclonal antibodies, which have to be administered frequently and in high doses, CYT007-TNFQb represents an active immunization that is expected to have a long-lasting effect and thus allow for more convenient dosing schedules.

TNF-α, a cytokine predominately produced by macrophages, is a potent inducer of inflammatory responses and a key regulator of innate and adaptive immunity.

For its Immunodrug™ candidate, Cytos Biotechnology has selected an appropriate peptide of TNF-α that is directionally placed onto the highly repetitive carrier particle Qb (a virus-like particle) using the Immunodrug™ technology. The normally non-immunogenic peptide is now presented to the immune system in a highly organized array and has the ability to induce strong anti-TNF-α antibody responses.