The use of cells as a therapeutic treatment, certainly has the potential to  address critical unmet medical need. Unfortunately, however, besides being still experimental,  rules and regulations of the FDA and EMA for medical products,  and financial concerns via patented products play an essential role in respect of government sponsored health care systems and its related budgets.

Let’s review the unmet medical need and cost concerns first before we go to the fast track approval intention of stem cell therapies in Japan, obviously understanding that regenerative and stem cell medicine cannot be regulated in the same way as traditional chemical and biological based drugs.

The human cell can carry out functions that cannot be performed by small molecule drugs of present pharmaceuticals or by targeting drugs developed and market by pharmaceutical and biotech firms. Those drugs are designed to treat symptoms mainly, respectively trying to reduce progression of illnesses.

More than four decades ago, cells were first used, successfully, in bone marrow and organ transplants. Today with the rapid advances in cellular technology and Know how, researchers are able to manipulate cells to create better targeted and more effective therapies.

Nearly every week we are learning about new breakthroughs in  stem cell research  and related genetic  technology.  We have already seen that, for some medical applications, cell therapies are obviously better equipped than small molecules or genetically engineered drugs. For instance, individually tailored induced pluripotent stem cells might be used to regenerate damaged organs or tissues, a clear indication that curing is eventually possible via developing personalized therapies by using autologous cells and tissues.

The advantage of iPSC of becoming any cell type is, however; also a disadvantage as iPSC, like embryonic stem cells, may during the application process form unwanted cells  in the patient. The discussion whether cell treatment is safe or not, therefore,  cannot be ignored and there are many  papers regarding this subject with pro and cons. I do not intent to join this discussion but  like in this connection use the diagram in,  which shows there are risks but also potentially ways to reduce this problem by  using own stem cells.

The risk of stem cell therapy obviously in general increases with the change of source and its manipulation. The safest cells as far as we presently know are apparently our own adult stem cell. As iPSC are “induced” i.e. manipulated  and manufactured in a Lab,  they are apparently more dangerous in respect of potentially forming tumors.

In the latest breakthrough, a University of Wisconsin-Madison research group has, however, converted skin cells from people and monkeys directly into a cell that can form a wide variety of nervous-system cells — without passing through the do-it-all stage called the induced pluripotent stem cell, or iPSC. These cells are not yet mentioned in the above Stem Cell Risk table and should be positioned somewhere next to “own Stem Cells”.

Bypassing the ultra-flexible iPSC stage was a key advantage, says senior author Su-Chun Zhang, a professor of neuroscience and neurology. “IPSC cells can generate any cell type, which, however, could be a potential problem for cell-based therapy to repair damage due to disease or injury in the nervous system.”

In particular, the absence of iPSC cells rules out the formation of tumors by pluripotent cells in the recipient, still a major concern involving stem cell therapy.

A second advance comes from the virus that delivers genes to reprogram the adult skin cells into a different and more flexible form. Unlike other viruses used for this process, the Sendai virus does not become part of the cell’s genes.

I believe that scientific advances  if better coordinated with clinical activities could help to depart from  the present  approach of “treating symptoms”  to more hospital oriented  “personalized therapies”  where autologous stem cells are harvested, minimally modified and directly re-administered  at the patient.

Like this,  cost benefit ratio of treating illnesses  and quality of life equations will most likely become better manageable. The present approach by using chemical or biological designed drugs is a costly lifetime activity, once therapy starts,  and as we can see from recent healthcare discussions with most governments, unfortunately, its costs are unsustainable.

Personalized therapies using autologous cells and gene technology to stimulate the body own immune and regeneration system, may become a once or few time treatment which may not have the lifetime cost of present medical drug approaches.

As an example MS treatment with new oral FDA approved medication  costs about $ 75,0 K to $ 80,0 K every year, direct and indirect costs included. There is certainly a cost advantage for those paying for the treatment when applying even experimental stem cell treatments, especially when considering that quality of life of those affected may improve considerably.

Well, there are already some examples even in clinical trials for diabetes under way, where autologous cells are harvested from a patient and treated  which can be explained as “trained to behave correctly” and returned after this reorientation back to the patient to fulfill its corrected and correct function.  For more details please see the stem cell educator equipment and approach as shown in our BLOG Jan. 8, 2013; Global development of diabetes and potential cure of patients……

In this case, Hospital Know how, clinical protocols and scientific experience are intelligently applied directly in a hospital / clinic at a patient by using his own stem cells, which are then stimulated via modern cell equipment to “behave” correctly in the patient’s body.

Most important is that scientific Knowledge, the proof of concept, is fully applied in practice in such a case that the knowledge base in hospitals is enhanced further.

Any Cell treatment, therefore, should be regulated differently from chemical and biological drugs, especially in respect of its approval process.  This does not mean that it should not centrally registered in accordance with a standardized protocol with all positive and negative results, in the contrary, only instead of imposing the phased clinical trial model a new regulation is needed to help to develop the new medical approach.

Nearly all clinics and hospitals do have all needed licences to perform medical treatments according to FDA and EMA standards and some countries allowing those hospitals with this very high technological standard also stem cell treatments. Those clinics and hospitals involved have already gained considerable experience in stem cell treatment. In this connection we like to mention the Stem Cell Institute in Panama and their valuable input in stem cell harvesting from adipose tissues and its therapeutic use in Arthritis and Sports Injuries, just as an example. There are many more in China, India, Malaysia and other more open minded countries.

The question often asked are they legal? Yes, they are in the frame work of their countries, but as clinical trails must be registered and approved by the FDA and should not be paid by patients, the often required protocol of proof of safety and efficacy  is not documented in the FDA way but according to the respective hospital standard only.

While western countries try to solve the issue by debating politically what is the right approach to stem cell therapy, i.e. “following the FDA protocol religiously or allowing a pragmatic application of clinical know how “ which is a typical endless debate about what is first “the chicken or the egg”, and will not result in any significant progress. Progress will come from those countries being more pragmatic by applying what scientifically already was successful in various experiments and was revealed in scientific papers!

As mentioned before cell technology has not only the potential, to cure an illness, but also will have a long termed positive effect on financing health care. This is the second main topic of health care because besides the costly approval process, the treatment itself, once initiated, becomes quite expensive for the health care payer.

We have analysed as an example the health care costs and the prevalence of Arthritis, a truly painful illness of those affected, to see how many people are affected in their quality of life and the cost burden of the relevant healthcare system.

Arthritis is a large and growing public health problem in most countries. In  the  United States, the annual costs are at $128 billion (2010 Data), and continues to be the most common cause of disability. With the aging of the population, even assuming that the prevalence of obesity and other risk factors remain unchanged, the prevalence of doctor-diagnosed arthritis and arthritis-attributable activity limitation (AAAL) is expected to increase significantly by 2030. Based on an update of the National Health Interview Survey (NHIS) from 2007—2009 in the US,  the analysis found that already in 2009 about 22.2% (49.9 million) of adults aged ≥18 years had self-reported doctor-diagnosed arthritis, and 9.4% (21.1 million or 42.4% of those with arthritis) had AAAL. Among persons who are obese, an age-adjusted 33.8% of women and 25.2% of men reported doctor-diagnosed arthritis.

The yearly cost (average) based on this NHIS analysis (2009) for Arthritis per patient in the US is when using the above global data, surprisingly only about:

2.265,00 USD

Treating patients symptoms  with a cost of about 2.2 K USD per person is certainly economically viable, considering that a stem cell treatment may cost much more than the yearly cost per patient, but certainly this “thinking model” is not really healthy for those suffering the nearly unbearable pain and the overall cost burden!

Having worked many years in senior management in the pharmaceutical industry, I feel, there is something wrong in this new medical approach with stem cells.

Innovation and this include, Innovative medicine, must not only improve the quality of life of patients, but in our economic reality, it has to be also cheaper or at least not more expensive than the present cost of treating a certain illness.

Therefore patenting stem cells of people for profit is possibly not the right way to advance with this alternative medicine. So, what is wrong with this potential new curing medical treatment, besides being seen by the authorities as poorly experimental with its need to be well regulated due to safety reason? ——–Very simple, the very high price tag which comes with this potential cure. Basically, these high costs are stimulated by government regulations and policy as local treatment is red taped it is forcing people to go abroad to be treated with even higher costs.

Personalized medicine, therefore, should become a local hospital therapy where autologous cells, repairing damaged tissues or organs at a competitive cost within the hospital structure.  Otherwise we will face the same difficult situation as we see in modern biological e.g. cancer treatments were for an example NICE, UK is reviewing cost benefit ratios and improved quality of life with certain drugs in order that the government approved health care budget is capable to pay for this new treatment. Often new drugs, although in general approved, are not reimbursed and, therefore, applied only in particularly limited cases.

If there would be unlimited funds available by the governments it would be a different scenario, but as long as governments are using taxpayers money to run the state and its organisation in the way they do, it appears to be unlikely.

So what can we learn from this? Well,  any innovation has to be not only an improvement of the presently used method, product or services, but it need to be also competitive with present treatment methods. If stem cell treatment, beside the regulatory hurdles  will not be affordable by payers involved, it will also due to this additional reason very slowly, if at all, advance.

The faster we answer those questions and make stem cell treatment competitive, the faster this treatment will enter mainstream treatment. Therefore, hospitals should involve them strongly in treating illness with patients’ own stem cells to get experience and find ways to reduce treatment related costs.

If cell treatment should become the new pillar of treating patients not only science and its application has to leapfrog, but also the cost benefit ratio needs to leapfrog meaning not exploding the payers budget further, but implode it so that the chronically deficit in healthcare becomes manageable.

One company, Cytori Therapeutics, is trying to balance costs and treatment benefits with its novel “Celution System” harvesting stem cells from the patient’s fat tissue to re-inject them into the targeted area of need as quickly and efficiently as possible.

The model shown in the photo is the current version of the Celution. It’s about the size of a small washing machine, with a user interface, a canister that holds the patient’s fat tissue, and a port where the doctor can insert a syringe to remove the filtered cells. The process takes about one hour to harvest about a liter of the patient’s fat tissue and to transform it in the Celution system to a syringe with 5 cc’s of what looks like cloudy red liquid. This liquid is the patient’s own stem and regenerative cells.

This idea of Cytori Therapeutics is  “Facilitating the physician or the hospital to have access to the cells of the patient –in a single procedure, at the bedside– with pharmaceutical-grade cells, and very inexpensively.”

Forty-five patients with heart diseases are being treated in a randomized, double-blind clinical trial at this moment in the US. By the end of this year (2013), according to the company’s chief science officer Marc Hedrick, the results should be in, and he is hopeful the company can launch a larger definitive clinical trial to gain FDA approval for Celution as a medical device. There is some hope that stem cell treatment will eventually progress faster and finally support patients with those medical needs so far unmet by existing drugs and treatment methods at competitive costs.

The discussion we often see regarding illegal use of stem cells appears to be extremely irrational considering the FDA drug approval. Often even for approved drugs,  we can read that there are warnings, drawing attention to some “accepted” side – effects. Beside this,  it is internationally proven that the use of approved drugs in “OFF Label” application is truly high, i.e. the use of the approved drug for any other, however, not approved therapy is tolerated! This makes you wonder why there is such a political activity around stem cells as a drug!

The most recent information to support stem cell therapies is coming from Japan where Japan’s Health authorities apparently understood that with the present time consuming and expensive regulation, for drug approval we are not able to manage well, stem cell therapy and its development.

The move comes in response to the potential offered by its homegrown induced pluripotent stem (iPS) cell technology, which netted Shinya Yamanaka, of the University of Kyoto, last year’s Nobel Prize in Medicine or Physiology. The Japanese government already flooded the field with more than 20 billion yen ($206 million) in a supplementary budget announced earlier this year, and it’s expected to allocate another 90 billion yen into the sector over the coming decade.

Under the Pharmaceutical Affairs Law as it currently stands, regenerative therapies, like small-molecule drugs, must undergo three phases of costly and cumbersome clinical trials to get approval by Japan’s Pharmaceutical and Medical Devices Agency.

The proposed amendments to the pharmaceutical law will create a new, separate approval channel for regenerative medicine. Rather than using phased clinical trials, companies will have to demonstrate efficacy in pilot studies of as few as ten patients in one study if the change is dramatic enough, or a few hundred when improvement is more marginal.

According to Toshio Miyata, deputy director of the Evaluation and Licensing Division at the Pharmaceutical and Food Safety Bureau in Tokyo, if efficacy can be “surmised,” the treatment will be approved for marketing. At that stage, the treatment could be approved for commercial use in Japan and, crucially for such potentially expensive treatments, for national insurance coverage.

This retooling of Japan’s drug authorization framework, being on its way to becoming law, could produce the world’s fastest approval process specifically designed for regenerative medicine. “I don’t know of any other countries that have broken out with a separate and novel system for cellular therapies”, says University College London regenerative medicine expert Chris Mason, who recently met with Japanese policy makers to discuss the law.

Well if Japan goes ahead with this legislation illnesses like multiple sclerosis or cancer where yearly costs for payers are much higher  than for arthritis will certainly get a stem cell boost, as technology and treatment Know how is already available in many places globally.

Asian countries and governments again show a pragmatic approach to newly applied science. Will we, in the so called advanced western world, again become bystanders like in various key industries, now  clearly dominated by Asian companies, because their governments support the real future vision and entrepreneurship by developing the legal framework to support the fast adaptation of experimental science into applied science.

We hope that this “Japanese fast track approval  idea” will flourish and shall induce a fast rethinking process in Western countries. A supportive legal framework combined with quickly advancing stem cell Know how and equipment lead application, like by Cytori, which is already approved in Europe, will give a big push to stem cells and its therapeutic application.  Western countries, “not adopting to this new reality”, again will loose technological leadership and may each time more be considered as the “new undeveloped countries of the 21st Century”.

ARISTOLOFT, May 26, 2013