US vs Regenerative Sciences Comes to End

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A court case we blogged a fair amount about even before it started (see the first post in 2008) appears to have finally come to an end in the DC Circuit Court's decision to uphold the ruling in favor of the FDA.

United States Court of Appeals 
FOR THE DISTRICT OF COLUMBIA CIRCUIT 

Decided February 4, 2014 

No. 12-5254 

UNITED STATES OF AMERICA, 
APPELLEE 

v. 

REGENERATIVE SCIENCES, LLC, A CORPORATION, ET AL., 
APPELLANTS 

Appeal from the United States District Court 
for the District of Columbia 
(No. 1:10-cv-01327) 

It has been an interesting ride.  Chris Centeno and his partners (and investors) have been the lightning rod for a lobby and debate around the right way to regulate the use of cells therapeutically - particularly one's one cells.  The arguments became more sophisticated as the case wore on and, as so often happens, the ground shifted considerably while the case was ongoing.  The case and Chris Centeno's unparalleled commitment to the cause has contributed significantly to a debate that is important to have and I suspect is not over simply because the case is done.

Dr. Centeno and I have had our differences but now is the time to recognize his contributions to the debate and, more importantly, to the field. We look forward to his future contributions to developing robust, cell-based treatments for patients.

FDA 1. RSI 0. Regenerative Sciences (Regenexx) vs FDA (2012)

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As followers of this blog will know I've been blogging about Regenerative Sciences and predicting their eventual run-in with the FDA since my first post in September 2008 (Cell Therapy is Not the Practice of Medicine) and again in February 2009 (Regenexx vs the FDA 2009).  When the FDA finally proceeded with an injunction against RSI in August 2010,I helped spread the news (here).

I've watched the development of the fight between RSI and the FDA with interest.  In September 2001 I posted a rather lengthy commentary about the potential impact of the case (Potential far-reaching implications of the ongoing fight over point-of-care autologous cell therapy.

Since then I have welcomed other bloggers and commentators who are now following and commenting on the case much more closely and frequently than I including @LeighGTurner (on Twitter) and Paul Knoepfler (@PKnoepfler on Twitter and his Knoeplfer Lab Stem Cell Blog).  Recently I enjoyed being interviewed by Paul on the issue of unregulated stem cell activity and touched on the case for his blog.

Consequently I read with interest yesterday's federal court ruling upholding the FDA's injunction against RSI and the immediate commentary from the New Scientist, Stanford's Scope Blog and Knopfler's multiple posts (here and here). As a long-term follower of this case, I've been asked to comment.  Here is my brief reaction:

This is a case that was always destined for the appellate courts regardless of which way the initial court ruled.    The fact the federal court ruled in the FDA's favor certainly now sets the onus on RSI and what is anticipated to be a gamut of intervenors but taking this case to the appellate courts is what the legal team have anticipated and legal arguments designed for all along.

This is just the beginning of what will be a long and interesting battle.  The ruling was nothing more than the granting of an injunction in response to the government's motion for summary judgement.  In granting the injunction the court  agreed with the government's position that it was acting under the authority given it under the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 321(g) but it provided little-to-no rationale for its ruling.

The court chose, in its wisdom, not to address the bulk of the RSI's legal arguments which are largely jurisdictional in nature. These are the kinds of arguments which the lower courts prefer be dealt with by appellate courts and frankly the judge did us all a favor by ruling quickly, succinctly and punting the case where we all knew it was inevitably headed.

In my opinion, other than chalking one up in the government's win column there is little to be gleaned from this ruling in terms of how RSI's arguments will be received in appellate court.  The interesting day is yet to come.

In terms of a short-term practical impact, frankly I see very little.  RSI has already ceased distributing Regenexx within the US so there will be little-to-no impact there.  As for the potential impact on other companies or clinics who might be operating on the fringes of FDA regulation within the US, I suspect it will be business as usual.

Most of the clinics/companies offering cell-based treatments/products which are arguably in contravention of FDA regulation are operating under the clear knowledge of what they are doing and where the FDA stands with respect to the treatments/products they offer and yet they persist and continue.


 For the truly fraudulent there is the risk of criminal charges and/or litigation but for those companies or practitioners who are operating in this shade of grey which are not shady (and they do exist), the  risks associated with this practice are barely higher than in the routine practice of medicine. 


In reality, with the exception of the most fraudulent examples, it takes a fair long-time for the FDA to catch up with these folks and there is good money to be made in the interim.  When they get caught, they will stop. If they've recouped their initial investment (which is nominal and the margins are high) there is very little penalty to this course of action.  Perhaps they set up shot elsewhere or simply enjoy the proceeds.  I doubt we will see much of a slow-down of this kind of activity.  Indeed it may strengthen the resolve of those committed to the cause.

In my opinion yesterday's ruling was in interesting and important milestone in a continuing evolution in the debate of how best to regulate the use of cells in treating people but I'm not sure it's the seminal pivot point that some believe.  I suspect we will not see any radical shift in terms of FDA or industry activity until (if then) the appellate courts rule.

Just my two cents....

--Lee

Potential far-reaching implications of the ongoing fight over point-of-care autologous cell therapy

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The FDA recently issued an untitled letter to Parcell Laboratories and its contract manufacturing organization, New England Cryogenic Center (NECC), pertaining to the product PureGen™ Osteoprogenitor Cell Allograft intended for the "repair, replacement, reconstruction of musculoskeletal defects". The letter stated:

"The PureGen™ Osteoprogenitor Cell Allograft is not the subject of an approved biologics license application (BLA) nor is there an IND in effect. Based on this information, we have determined that your actions have violated the Act and the PHS Act."

This would appear to be an indicator that the FDA does not intend to relax enforcement of its view of how autologous cell therapies are to be regulated despite its ongoing litigation on this very subject with RSI.

As followers of this blog know, since the battle's inception in 2008 I have followed the case of Regenerative Sciences, Inc and their war with the FDA over their right to provide certain autologous cell therapy treatments to patients in certain circumstances without FDA approval. My first blog entry on the topic was in September 2008 in which I pointed out that the FDA had written a letter to RSI that July taking issue with some of their practices.

My next blog on the subject was February 2009 in which I concluded "I think the FDA is building its case and a showdown is on its way to Denver-town."

At the advice of legal counsel, I pointed out in a March 2010 blog entry that my reference to FDA's July 2008 letter to RSI was not officially a "warning letter" as that is defined and as I had referred to it but rather an "untitled letter". I also commented that FDA's lack of enforcement action against RSI to-date was emboldening medical practitioners into thinking FDA was reconsidering their position on the legality of providing autologous, expanded cells to patients outside of an FDA-cleared IND or BLA.

I took some satisfaction in announcing on my blog in August 2010 that the FDA had finally taken action against RSI. My satisfaction was not rooted in a belief that the FDA is right (I've always been agnostic as to which side is right) but in the sense that things had occurred as I had predicted they would.

The action the FDA chose to take against RSI was to seek an injunction against RSI from continuing to provide the "offending" treatment - a version of the Regenexx™ procedure using mesenchymal stem cells (“MSCs”) grown outside the body after harvest for the later infusion back into the donor-patient for the treatment of various orthopedic conditions - which the FDA alleges is a "product" falling under its regulatory authority but for which RSI has never received any FDA clearance to provide to patients.

RSI counterclaimed against the United States, challenging the FDA’s authority to regulate the Regenexx™ Procedure in question and challenging certain FDA regulations. The United States moved to dismiss Defendants’counterclaims and for summary judgment.

I have continued to follow the case relatively closely through a number of source (see this sample media coverage in OthosSpineNews) as it continued to progress. Last month, for example, a blog I follow posted an eloquent case in support of RSI's position with the help of Mary Ann Chirba, J.D., D.Sc., M.P.H. of Boston College Law School.

So it was with much interest that I was recently notified of an order issued by the court which appears to have the potential to take the case in a very unexpected direction with enormous potential ramifications.

The context is that the judge was reviewing the FDA's motion for summary judgment, RSI's response, and FDA's reply when the judge issued this order to show cause.

At its essence the Judge has ordered the FDA to file a brief no later than 26 September showing the court why the term “chemical action” applies to stem cells. It is is a short Order the core of which reads as follows:

The Government finds its definition for a “drug” in the FDCA: “The term ‘drug’means . . . articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals” and “articles (other than food) intended to affect the structure or any function of the body of man or other animals.” 21 U.S.C. § 321(g)(1)(B)&(C).

This definition, at least as to subsection (C), would be broad enough to encompass a boot on a patient’s ankle to hold it secure after ankle surgery. The Court doubts that was Congress’s intent.

Neither party references the definition for “device,” found in the statute at 21 U.S.C. § 321(h). A “device,” is a certain kind of “article” used in diagnosis, cure, mitigation, treatment or prevention of disease, 21 U.S.C. § 321(h)(2), but which, presumably unlike a drug, “does not achieve its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of its primary intended purposes.” 21 U.S.C. § 321(h).

These contrasting definitions immediately raise the question of why the Court should not interpret the meaning of the word “drug” to include not only an article for use in diagnosis, etc., and intended to affect the structure or function of a patient, but also an article that “achieve[s] its primary intended purposes through chemical action” and which is “dependent upon being metabolized for the achievement of its primary intended purposes.” Id.

The United States is ORDERED TO SHOW CAUSE why the Court should not read the definition of “device” at 21 U.S.C. § 321(h) as informing and restricting the definition of “drug” at 21 U.S.C. § 321(g)(1)(B)&(C).

It will be most curious to see how the FDA argues out of the corner that many believe the Judge has painted the agency. The FDA recently defined “chemical action” in its draft "Guidance for Industry and FDA Staff: Interpretation of the Term “Chemical Action” in the Definition of Device under Section 201(h)of the Federal Food, Drug, and Cosmetic Act". What is curiously absent from the document is any mention of cells or HCT/P’s despite CBER’s approval stamp on the document.

Another line of argument centers around whether cells - notably 'stem' cells - are “metabolized" as that term is defind.

If one extrapolates the ramifications of where the court appears to be currently leaning, the implications of this judgment may have far-reaching implications for biologics in general well beyond cell therapy and certainly well beyond autologous cell therapy.

As some quite logically argue, one potential scenario is that this judge rules all biologics fail to fall within the legislative "drug" definition. The argument goes like this. The drug regulations live under title 21, which has narrow definitions for what constitutes a drug. The FDA’s authority over biologics comes from title 42, which is merely to control communicable disease transmission in transplants, with no authority to take the drug provisions from title 21 and apply them to title 42. So the agency is risking a loss of control over all biologics.

What’s curious here - and perhaps somewhat ironic for RSI at this stage - is that they only ever set out to challenge their ability to regulate autologous cells used by a physician as part of his or her medical practice yet now the FDA's authority to govern all biologics is currently under question.

The fact that I cannot fathom the courts striking FDA's jurisdiction over all biologics when the dust settles on this case does not make the arguments any less compelling and it does leave open the possibility that a lower court Judge such as the one presiding over this case may be inclined to make a ruling which essentially ensures the issues are punted to the appellate courts for a more considered ruling. In such circumstances, even if the FDA were to prevail at the end of the day (perhaps a decade down road) the uncertainty such a ruling would rain down on the sector would be commercially stifling - even if if were just limited to autologous cell therapy let alone if were any broader.

My dated and unpolished law degree can only take this analysis so far and anyone interested in some further but delightfully light and practical reading on the potential ramifications of the case could do no better than read a paper published recently by the relevant practice groups at the law firm K&L Gates entitled "Cultured Stem Cells for Autologous Use:Practice of Medicine or FDA Regulated Drug and Biological Product in which they review the case and its potential implications - the latter of which the authors are not guilty of underestimating in the following concluding sentence of their analysis:

The court’s decision will, to a large degree, dictate the types of legal strategies and business models that will be necessary to successfully perform stem cell procedures in the future.

_____________

post-script: The potential stink of commercial uncertainty wafting from this case is even more egregious when combined with the uncertainty around what to expect from the FDA in its much-anticipated and typically overdue guidance on adipose-derived cell therapies.

Rumor has it that the FDA is leaning toward considering most (if not all) means of deriving cell populations from adipose tissue (typically lipoaspirate) to be governed as what we colloquially refer to as a '351' thus taking it out of the purview of the practicing physician and into the hands of companies prepared to follow the traditional "drug development' model for new medicines. The rationale here is that the mechanical and/or enzymatic digestion required to separate the desired cell populations from the stroma take the process beyond "minimal manipulation'.

Watch for this guidance from CBER OCTGT in the weeks to come and/or any relevant rulings by the Tissue Reference Group. This would be a serious blow to those building business models around point-of-care, autologous adipose-derived cell therapy treatments.

What makes this even more interesting is the pace of which US-based medical practitioners (and/or companies supporting them) are adopting and selling autologous cell-based products, services and/or treatments for sundry indications in ways which many would argue are apparently in obvious and flagrant disregard for the FDA's regulatory authority over such treatments. Included for consideration on such a list would be the following:

IntelliCell Biosceinces

eternaMD

Arizona Stem Cell Center

.

FDA files injunction again Regenerative Sciences citing Regenexx violates regulations

For those of you who follow this blog, you'll imagine my surprise to wake up the morning to the following announcement from the FDA:

_____________________________________________________________

FDA NEWS RELEASE

For Immediate Release: August 6, 2010

Media Inquiries: Shelly Burgess, 301-796-4651, shelly.burgess@fda.hhs.gov

Consumer Inquiries: 888-INFO-FDA

FDA Seeks Injunction Against Colorado Manufacturer of Cultured Cell Product

Violations of current good manufacturing practice and labeling requirements cited

The U.S. Food and Drug Administration is seeking an injunction in federal court against Regenerative Sciences LLC, of Broomfield, Colo., citing violations of current good manufacturing practice (cGMP) that cause its cultured cell product to be adulterated. The product is also misbranded due to the lack of adequate directions for use and the failure to bear the “Rx only” symbol.

The company’s cultured cell product is derived from a patient’s bone marrow or fluid surrounding the patient’s joints (synovial fluid). The cells are grown, processed, and mixed with drug products outside the body before being injected back into the patient.

Regenerative Sciences’ cultured cell product is not approved by the FDA, and no adequate and well-controlled studies have been done to demonstrate its safety or effectiveness for any indication.

“FDA recognizes the importance of the development of novel and promising new therapies,” said Karen Midthun, M.D., acting director of FDA’s Center for Biologics Evaluation and Research. “However, when companies like Regenerative Sciences fail to comply with FDA laws and regulations, they put the public’s health at risk.”

The complaint for the injunction was filed Aug. 6, 2010, by the Justice Department on behalf of the FDA in the U.S. District Court for the District of Columbia, against Regenerative Sciences and three of its employees, Christopher J. Centeno, M.D., John R. Schultz, M.D., and Michelle R. Cheever. The injunction would permanently prevent the company and cited individuals from adulterating and misbranding the cultured cell product while the product, or one or more of its components, is held for sale after shipment in interstate commerce.

Regenerative Sciences has agreed to cease production of the cultured cell product while the case is pending.

The FDA warned Regenerative Sciences about its cGMP violations as recently as June 2010. The company failed to make sufficient corrections, and the conduct of the individuals cited in the complaint demonstrates refusal to comply with the law.

Errata Statement re: Regenexx

It has been pointed out to me by legal counsel that the 25 July 2008 letter from the FDA to Regenerative Sciences, Inc regarding what FDA observed as apparent "violations" of FDA regulation by Regenexx, was not a "Warning Letter" as that term is officially defined but rather an "Untitled Letter" which has less or no formal effect.

My previous reference to the letter as a "warning letter" was a colloquial rather than legal use of the term. In any event, to avoid possible confusion, I hereby formally point out that the letter was not a "Warning Letter".

Despite the FDA's observations of what it then said appeared to them as Regenexx "violations" of FDA regulation in that Untitled Letter, since the date of the letter the FDA has not followed up with any Warning Letter, Cease and Desist Letter, or sought any other relief in court either in an action of its own or in the action brought against the FDA by Regenerative Sciences, Inc.

This fact has emboldened many to believe that the FDA will not take any action to remove Regenexx from the market despite its observations in 2008 that Regenexx appeared to violate the existing FDA regulatory framework.

Some take this one step further and believe that by its lack of action the FDA has demonstrated it now believes the product does not, in fact, violate the regulations. Others are convinced the FDA's lack of action is merely a lack of action and not a change of conviction. In the face of a lawsuit by RSI, after all, the FDA has to pick its battles carefully.

Only time will tell...

Cell Therapy Industry HiLites 2009-05-26

This week I'm ROTFLMAO loving this cartoon so I thought I'd share the chuckles (thanks to www.onstartups.com). I can't tell you how many times in the past years I've seen the inevitable 'hockey stick' market projections graph from companies, analysts, and investors when discussing the coming 5 years in the cell therapy sector. It's become a standing joke about how we just keep pushing the hockey stick out to the right but the curve is inevitably the same. This pokes a little fun at this much maligned tradition.

Maybe it's just because I'm Canadian that I love this so much but c'mon the beloved hockey stick has become almost more a marketing tool than the venerable piece of sports equipment every Canadian boy must own! Maybe we can adapt this new hockey stick model to give the over-used Gartner cycle a run for its money!

Down to business...

I was told last week that Senators have been inviting people to Capital Hill to speak to them about FDA regulation of adult stem cells perhaps at the instigation of Chris Centeno's lobbying through ASCTA (www.stemcelldocs.com) that the medical use of moderately expanded autologous adult stem cells should not be regulated by the FDA but rather self-regulated by physicians. This could, of course, have serious implications on business models for autologous cell therapy companies. I've heard nothing of the Senators asking for ISSCR or ISCT counsel to-date. It would, of course, likely be Centeno's position that anyone involved in those orgs are "pharma hacks" as he has accused me of being.

ASCTA which is comprised of physicians none of whom are acknowledged leaders in stem cell research recently proudly announced the release of their stem cell guidelines which they suggest should replace FDA regulation. In what appears to be simple ignorance of the years of work being done by AABB & FACT, ASCTA described their guidelines as "the world's first clinical guidelines to allow U.S. doctors to safely begin using the patient's own stem cells to treat disease." Their lab practice guidelines contain such gems as:

• Any facility used in the processing A-ASC’s must be of suitable size, construction, and location to prevent contamination.
• The facility should be in a good state of repair.
  
• Equipment used in the facility should be adequately maintained
• In humid areas, dehumidifiers should be used to control the spread of infectious agents in the lab.
• Any reagents used must be approved for human use (where practical).

In an online posting entitled "The FDA is Killing Adult Stem Cell Therapy Thus Killing Patients", ASCTA supporter, Don Margolis, states:

In a startling new interview on stem cell research and adult stem cells in the near future, Dr. Christopher Centeno warns that Big Pharma and the FDA are teaming to control the use of a person’s own stem cells thus slowing innovation and the use of Adult Stem Cells to help patients now.

FINANCIAL

ReNeuron Group plc (LSE: RENE.L) has raised the £3 million it announced it intended to raise. ReNeuron recently received regulatory approval to commence a Phase I clinical trial in the UK with its lead ReN001 stem cell therapy for disabled stroke patients. The Company is developing stem cell therapies for a number of other conditions, including peripheral arterial disease and diseases of the retina. ReNeuron has also developed a range of stem cell lines for non-therapeutic applications – its ReNcell® products for use in academic and commercial research. The Company’s ReNcell®CX and ReNcell®VM neural cell lines are marketed worldwide under license by USA-based Millipore Corporation.

**

Pfizer expects to pump $100 million into its international stem cell development program which aims to focus both on small molecules that work by modifying cells in the body and cell therapy where the cells are manipulated outside the body. The first major use of the Pfizer money is for a collaboration with University College London (UCL) for the treatment of certain forms of blindness through the London Project to Cure Blindness. The collaboration will attempt to develop stem cell-based therapies primarily for wet and dry macular degeneration (AMD), which Pfizer has the rights to progress through clinical trials and then commercialize. Pfizer’s work on this could potentially provide a boost for the cash-strapped and searching-for-a-buyer, Intercytex Group plc (AIM: ICX), whose involvement on the London Project could yield cash royalties. But that's not where the Pfizer-Intercytex connection may end, apparently. Reports indicate that Pfizer is in fact eyeing the troubled Intercytex as a potential acquisition or investment. The company is on the auction block and actively seeking suitors.

**

Cytori Therapeutics, Inc. (NASDAQ: CYTX) expected to close a private placement for $4.2 million by May 11. No word yet...

**

Cord Blood America, Inc. (OTCBB:CBAI) has received a commitment for up to $2.3 million of new funding to acquire or build its own state-of-the-art laboratory for the storage of multiple stem cell products including umbilical cord blood stem cells. Less than two years ago the company signed a deal with Progenitor Cell Therapy LLC to process and store their stem cell units on a contract basis. Now CBAI says having their own facility will over the long term reduce their costs for both the processing and storage and additionally allow CBAI the flexibility and capacity to pursue new sources of revenue such as the storage of adipose tissue and peripheral blood stem cells processing and storage much easier than under the current structure of outsourced relationships.

**

Core Dynamics announced it has recently closed on a new financing round of US$17.9 million institutional and private investors. The money will be used to further develop the company's process for freeze drying human stem cells to be stored at room temperature.

**

Bioheart, Inc. (OTCBB:BHRT) announced today that its common stock is now being quoted on the OTC Bulletin Board (OTCBB) under the trading symbol "BHRT," the company's original ticker symbol.

CLINICAL

Aastrom Biosciences, Inc. (Nasdaq:ASTM) temporarily suspended enrollment and patient treatment in its U.S. Phase II IMPACT-DCM clinical trial following a report that a patient died at home after being released from the hospital following treatment in the trial. IMPACT-DCM is a clinical trial to evaluate the surgical delivery of autologous cells directly into the human heart muscle for the treatment of congestive heart failure associated with dilated cardiomyopathy (DCM) in both ischemic and non-ischemic patients. The patient's cause of death has not yet been determined and is the subject of a pending investigation at the clinical site. An independent Data Safety Monitoring Board (DSMB) will also assess the circumstances of the event. The Company has voluntarily suspended patient enrollment and treatment in the trial and the FDA placed the trial on temporary clinical hold pending an investigation.

**

ImmunoCellular Therapeutics, Ltd. (OTC: IMUC.OB ) (IMUC) announced that clinical data from the company's Phase 1 trial of its antigen-pulsed dendritic cell immunotherapeutic cancer vaccine ICT-107 for patients with brain stem glioma and glioblastoma will be presented at this year's ASCO. Having said that, they also said that while "encouraging data" was observed from the phase I trial of ICT-107, IMUC's primary focus going forward will be on its lead product candidate, ICT-121, which is an peptide-based "off-the-shelf" cancer vaccine that targets cancer stem cells and may have applicability to multiple types of cancer. IMUC anticipates filing an Investigational New Drug (IND) application in the third quarter of 2009 for a Phase I trial of ICT 121 in the treatment of glioblastoma (brain cancer).

**

Little-known, Memgen, LLC will be presenting results from a recently completed phase I clinical trial of its novel active immunotherapy product, ISF35, in patients with high-risk, progressive chronic lymphocytic leukemia (CLL), at next week's ASCO meeting. According to the study's principle investigator, Dr. Castro, one injection with no chemotherapy resulted in durable reductions in lymph nodes and spleen size in most patients and three of fifteen patients with rapidly progressing disease did not require any further treatment for more than one year. Based on the results from this single injection study, a phase II trial evaluating multiple intranodal injections of ISF35 in CLL has begun funded by - of all things! - the Food and Drug Administration at UCSD. The company believes the product is also positioned for use in lymphomas and solid tumor cancers.

**

Aderans Research Institute Inc. (ARI) announced it has launched Phase 2 of its clinical study on cell-based hair regeneration for men and women. The company's research is focused on developing a state-of-the-art tissue engineering solution to the regeneration of hair, taking actual hair cells--fibroblasts and keratinocytes, the two primary cell types within hair follicles--and promoting their growth in controlled laboratory environments. The research teams then recombine them and these "combined hair cells" are then placed in the patient's skin, where they are expected to elicit hair growth.

**

Cytori Therapeutics, Inc. (NASDAQ:CYTX) completed enrollment in the first study to investigate adipose derived stem and regenerative cells in chronic heart disease. The trial, named the PRECISE study, was designed as a double-blind, randomized, placebo controlled, dose escalation study specifically enrolling patients suffering from an advanced form of chronic heart disease, known as chronic myocardial ischemia, for which there is no generally accepted treatment. The trial enrolled 27 patients in a study involving the patients’ own cells extracted from adipose tissue and processed for delivery at the point of care using Cytori’s Celution® System. The cells were then injected back into the patients using the NOGA® XP System (Biologics Delivery Systems, Cordis Corp., a Johnson and Johnson company). Primary endpoints were safety and feasibility of Cytori’s Celution® System as part of a novel procedure for chronic heart disease.

A major attribute of the Celution® output is that it is comprised of multiple cells types. This, the company believe, contributes to multiple mechanisms of action, and thus increases the potential to restore heart function. The Celution® System used in PRECISE was configured specifically for cardiovascular disease, including proprietary processes and enzymes needed to achieve a level of purity required for vascular delivery.

COMMERCIAL

Cytori Therapeutics (NASDAQ:CYTX) and GE Healthcare, a unit of General Electric Company (NYSE:GE) announced an agreement by which GE Healthcare will commercialize Cytori's StemSource(R) technology in the North American stem cell banking and research markets. The StemSource technology includes automated equipment to process stem and regenerative cells found in adipose tissue, cryopreserve them or use them directly for research purposes. In January 2009, Cytori and GE Healthcare formed a separate agreement to commercialize Cytori's products in ten European countries. This includes selling the Celution(R) 800/CRS System in the European cosmetic and reconstructive surgery market as well as selling StemSource products in the European cell banking and research markets. The recent partnership is similar in nature to the European agreement, but is limited to the sale of StemSource banking and research products in the U.S., Canada and Mexico for 18 months starting in the second quarter of 2009. The agreement does not include U.S. commercialization of Cytori's Celution System, which is currently under review by the FDA.

**

Celsense, Inc. has announced the formal opening of its new and expanded R&D facility said to be a key component to Celsense’s commercialization strategy for its pre-clinical and clinical-grade molecular imaging agents used to non-invasively visualize and measure cellular activity and biodistribution. The company is now actively bringing both their lead research and clinical-grade cellular and molecular imaging agents to market over the coming months and is said to be collaboration with several academic and industry parties currently evaluating our products for potential use in their discovery research or clinical protocols.

Their clinical-grade Cell Sense reagent is a fluorocarbon tracer agent used to label cells in vitro then transplanted thus enabling investigators and clinicians to non-invasively track the administration and delivery of therapeutic and diagnostic cells in vivo using MRI. Applications include tracking therapeutic cells in regenerative medicine and immunotherapy applications, and observing localized immune system response by tracking populations of immune system cells. The research-grade V-Sense is an injectable fluorocarbon MRI tracer agent that labels leukocytes in situ, enabling the direct, non-invasive observation of immune system response and localized inflammation. Applications include observing change in immune system response to therapeutics and mapping localized disease such as certain cancers and infections.

**

After securing a $12M equity financing facility and closing a $1.5M private placement, formerly on-the-rocks Melbourne-based Prima BioMed (ASX: PRR), which had less than $500,000 in the bank at the end of December, is now preparing IND filing in the US for a phase IIb / III pivotal trial of CVac for ovarian cancer. As previously reported here, the company has also commenced CVac™ ovarian cancer treatments on selected patients in Australia made possible through the Australian Government’s Australian Regulatory Control Mechanism’s Special Access Scheme under the Therapeutic Goods Administration. Meanwhile the company is looking at taking the product to other countries as a means of generating cash flows in the short-term through the sale of CVac™ treatments. Now the company's executive director, Mr Martin Rogers, is touring North America in discussions with a number of hedge funds and other biotech focused investment funds about new investment and partnering opportunities for the commercialization of CVac.

**

Progenitor Cell Therapy, LLC has done a deal with NeoStem, Inc. (NYSE Amex: NBS) as their exclusive provider of commercial adult stem cells processing and storage. Progenitor founder, Andrew L. Pecora, has also joined NeoStem's Advisory Board.

**

NeoStem, meanwhile, - the new favorite company of alternative "medical" products promoter, Suzanne Sommers - has been busy the last few weeks creating a curious empire of sundry types of bedfellows. Recently the company announced it had signed an agreement to license the exclusive worldwide rights to a technology, with pending patent applications, developed by Vincent Falanga, M.D., Chairman of the Department of Dermatology and Skin Surgery at Roger Williams Medical Center, Providence, R.I. Dr. Falanga's stem cell product under development, Primcel, is a mesenchymal stem cell (MSC) product. Early clinical studies are said to indicate that Primcel can be used to accelerate or jump start healing of chronic wounds. Dr. Falanga's work seeks to develop a prepackaged product created from a patient's own cells, ready for physician use in a clinical setting, consisting of three applications over a 12-week period.

Almost in the same breath, the company filed a patent application claiming the proprietary stem cell technology of Vincent C. Giampapa, M.D., F.A.C.S. relating to cosmetic facial rejuvenation, which NeoStem first licensed in February 2009. Dr. Giampapa is director of the Giampapa Institute for Anti-Aging Medical Therapy, a board-certified plastic reconstructive surgeon and Assistant Clinical Professor of Plastic and Reconstructive Surgery at the University of Medicine and Dentistry of New Jersey. His cosmetic stem cell face lift technology is said to comprise a "non-surgical procedure for complete facial rejuvenation that involves injecting pluripotent cells, including stem cells, into the skin of individuals whose skin has lost its firmness and texture due to age".

Days later NeoStem announced it had signed an exclusive royalty-bearing license agreement for the Asia territory for a procedure developed by Regenerative Sciences, LLC and marketed for the treatment of chronic orthopedic conditions, under the name, Regenexx. Additionally, Regenerative Sciences, through its founder and CEO, Christopher Centeno, M.D., will serve as a consultant to NeoStem, Inc. in the area of stem cell therapy in orthopedics.

Undoubtedly Centeno will also embroil and leverage NeoStem in his fight with the FDA about the marketing of Regenexx in direct flagrance of FDA regulation. In any event this is clearly a solid "plan B" for Centeno should the FDA ever get around to shutting him down in the U.S. In the interim, Centeno continues to strengthen his network of supporters and is reportedly actively working Capital Hill for support for his fight.

To mix it up a little, NeoStem then announced they had signed a deal to promote and glean royalties from the sale of a liquid, nutritional supplement - AIO Premium Cellular Health. Not kidding. They have signed an agreement for Ceres Living, Inc., a developer and direct marketer of health and wellness products. AIO Premium Cellular Health was apparently developed in conjunction with NeoStem's scientists and Advisory Board members, based on certain nutraceuticals that have been shown to "optimize stem cell functions". The promotion of AIO is said to be "part of NeoStem's corporate commitment to advancing anti-aging and regenerative medicine therapies and technologies."

**

Novocell, Inc. announced that it has received U.S. Patent # 7,534,608 with with wide-ranging method claims covering the Company’s innovative stem cell therapy for the production of functional pancreatic, insulin-producing cells from human embryonic stem cells (hES). Novocell’s therapy is being developed as a method for the use of hES cells to replace insulin-producing pancreatic cells that are destroyed in people with diabetes.

**

Neuralstem, Inc. (NYSEAmex:CUR) recently published a reaction to a press release by StemCells, Inc. (STEM) refuting many of their statements in what has become a very public dispute. Included in the reaction is the claim that "the PTO upheld the patentability of Neuralstem’s core technology in May, 2006, in response to a challenge from STEM" and that the Neuralstem "patents are not being challenged in the PTO or in any of the suits with STEM".

**

This is not a cell therapy story but it could be. Takeda Pharmaceutical Company Limited (TSE: 4502) and IDM Pharma, Inc. (Nasdaq: IDMI) today announced that Takeda America Holdings, Inc., a wholly-owned subsidiary of Takeda (Takeda America), and IDM Pharma have entered into an agreement for Takeda America to acquire IDM Pharma. Takeda America has established Jade Subsidiary Corporation as a wholly-owned subsidiary to effect that transaction. Under the agreement, Takeda America will purchase all of IDM Pharma's outstanding shares for US$2.64 per share in an all cash tender offer followed by a merger.

You may recall that on April 1 last year (omen perhaps?), Cell Genesys, Inc. (“Cell Genesys”, Nasdaq: CEGE) and Takeda announced that the companies had formed a global alliance for the development and commercialization of GVAX immunotherapy for prostate cancer, Cell Genesys' lead product candidate then in Phase 3 clinical development. Under the agreement, in exchange for exclusive worldwide commercial rights to GVAX immunotherapy for prostate cancer, Takeda was to pay Cell Genesys an upfront payment of $50 million and additional milestone payments totaling up to $270 million relating to regulatory approval and commercialization of GVAX immunotherapy for prostate cancer in the United States, European Union and Japan.

This deal quickly unraveled when they decided to mothball both phase 3 studies of GVAX on statistical likelihood of failure. This was Takeda's big venture into cell therapy and it is an ugly, recent memory. Now they have bought IDM Pharma. They 've bought it for the company's primary asset, MEPACT, (mifamurtide), a macrophage activator drug therapy indicated for the treatment of non-metastatic osteosarcoma (malignant bone cancer) following surgical removal of the tumor (resection) in children, adolescents and young adults.

Here's the cell therapy part: IDM Pharma has 3 autologous cell therapy products currently on developmental hold as a means of perserving resources to get them to the home run on MEPACT. BEXIDEM is activated macrophages (Monocyte-derived Activated Killer cells or MAK® cells) for bladder cancer. UVIDEM, for melanoma, and COLLIDEM, for colorectal cancer, are both therapies using dendritophages (specialized immune cells derived from the patient's own white blood cells). It will be very interesting to see what Takeda does with these products, if anything.

**

Veterinary stem cell company, Vet-Stem, Inc, has now expanded from its US base into Canada, providing commercially available autologous, adipose-derived stem cell tranplants for horses and dogs.

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According to the Seattle Times which played a critical role in exposing what is now alleged to be potential fraud, CellCyte Genetics, "left a cashless zombie after the stock-touting campaign that lifted its value to $400 million faded away, says it has reached a tentative settlement in the Securities and Exchange Commission (SEC) inquiry into its activities" but it still faces a criminal probe and the "number of lawyers embroiled in the company's legal troubles have now outnumbered the company's peak work force".

MISCELLANEA

International Stem Cell Corporation (OTCBB:ISCO), the company behind human stem cells from unfertilized eggs (called “parthenogenetic stem cells”), submitted comments to NIH on their draft stem cell research guidelines issued by the National Institutes of Health (NIH) on April 17, 2009. ISCO then published its comments in a press release and then their CEO published a blog to address questions regarding their comments.

Genetics Policy Institute also submitted a letter to the National Institutes of Health (NIH) commenting on the Draft Guidelines for Human Stem Cell Research. The complete letter is available at www.genpol.org for public viewing.

**

The California Institute for Regenerative Medicine is working its way through Congress seeking $500 million in federal funds it hopes to apply toward guaranteeing the long-planned small-business loan program.

Forbes published what is actually quite an informative article on cell therapy medical tourism for a change.

Sign-off

If you've read this far you're obviously interested in the cell therapy industry. If you're on LinkedIn make sure you have joined the LinkedIn Cell Therapy Industry Group.

Thank you all for all your good wishes about the new addition to my family - my own little sample of regenerative medicine! Now I gotta go and spend some time with her before I'm enrolling her in college...

Remember. Cell Therapy Means Business.

Cell Therapy Industry HiLites 2009-02-13

A little slower week allowed for a little more in-depth analysis rather than just passing on the headlines. Hope you enjoy...

My post "Regenexx vs FDA 2009" has generated much discussion both on and offline from interested observers, Regenexx patients, and even Dr. Christopher Centeno himself. Some of that discussion has take place at KneeGuru.co.uk where there is an ongoing discussion thread about the Regenexx therapy and some of it has taken place here in the comments section of the blog. Dr. Cento has now posted an email he sent me last week as a comment to the blog for the benefit of all to see. This will continue to be a very interesting case to watch as the year develops and we see whether or not the FDA is satisfied to let this kind of clinical practice proceed.

FINANCIAL

I've always wondered who the investors are who, unlike me - despite my irrational optimism about cell therapies - buy public shares in such early-stage companies like GERN or STEM despite them being so many years away from having a commercial product. Nonetheless, I've always admired Geron's ability to move and capitalize on movements in its share price.

True to its talents, Geron Corporation (Nasdaq: GERN) announced today (Feb 13) the sale of 7.25 million shares of its common stock. The offering is expected to close on February 19, 2009. On February 12, the press release states, "the last reported sales price of Geron common stock on the Nasdaq Global Market was $7.77".

In an article entitled, "Geron's Stem-Cell Hype Soaks Investors", Adam Feuerstein from theStreet.com is reporting the shares were sold at a price of $6.60, a 14% discount to the stock's Thursday closing price of $7.77 and that the spot-financing deal grossed Geron about $43 million. Geron has not yet disclosed the sale price but is expected to so when the financing closes on Feb. 19. Geron shares fell over 14% to below $6.50 in Friday's trading.

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A little update on Northwest Biotherapeutics, Inc. (AIM:NWBS and NWBT; OTC BB: NWBO). Some of you will recall that NWBT went public on the AIM market mid-2007. NWBT's lead product is its DCVax^® platform technology that it is studying in multiple cancers. DCVax^®recently reported some positive interim data in ovarian cancer although their most advanced trials are in prostate and brain cancers.

Last May NWBT announed it had secured a loan of $4 million from Al Rajhi Holdings W.L.L. who held - at that time - in excess of ten per cent of the company's issued and outstanding common stock of the company.

In October the company announced it had entered into a Loan Agreement and Promissory Note with SDS Capital Group SPC, Ltd for $1 million with a maturity date of April 1, 2009. The company anticipated this would get them through November 2008.

In November, the company announced that it had obtained US$1.65 million in debt funding pursuant to Loan Agreements and Promissory Notes with SDS Capital Group SPC, Ltd (“SDS”) and a group of private investors with the Notes maturing April 21, 2009. The company expected this cash would get them through December 2008.

In December, the company announced that it had obtained US$0.5 million in debt funding from Toucan Partners and that these proceeds were expected to fund the Company’s cash needs into January, 2009.

In January, NWBT announced the settlement of a securities class action lawsuit by the payment of a $1 million settlement to be funded out of insurance proceeds. The case alleged that the Company misrepresented certain facts that resulted in the artificial inflation of the price of Northwest Biotherapeutics publicly-traded common stock between April 17, 2007 and July 18, 2007. The Company disputed the allegations of the lawsuit, and denies any such misrepresentation or that the shares of Northwest Biotherapeutics common stock were artificially inflated. Nevertheless the Company announced it was settling the lawsuit to avoid potentially expensive and protracted litigation. The Company also announced that the formal investigation by the SEC into the matter has been closed without any action taken.

Without doubt the lawsuit has severely impacted the company's ability to raise funds. Now that the legal action is settled and the SEC has gone away, their only hurdle is an impossible fund raising market and presumably only weeks left of cash. We will watch with interest.

CLINICAL

Osiris Therapeutics, Inc. (NASDAQ: OSIR) announced the final two-year results for the Company's trial evaluating Prochymal(R) for the treatment of acute myocardial infarction. The data showed lasting clinical benefit in heart attack patients. Prochymal is Osirs' proprietary formulation of adult stem cells designed to provide therapeutic benefit by controlling inflammation, promoting tissue regeneration, and preventing scar formation. The phase I double-blind, placebo-controlled study of 53 patients, which evaluated safety and preliminary efficacy, found heart attack patients receiving the intravenous therapy had lower rates of adverse events and significantly improved heart function. Study findings included:

• The trial met its primary endpoint demonstrating safety of Prochymal in the acute MI setting.
  
• Patients receiving Prochymal had fewer adverse events compared to placebo. A lower percentage of patients treated with Prochymal required repeat hospitalization.
  
• Patients receiving Prochymal had reduced incidence of cardiac arrhythmia. Patients receiving Prochymal had a significant and durable improvement in cardiac function.
  

"We are now advancing this program into a larger Phase II trial, focusing on patients with more severe heart damage," said C. Randal Mills, Ph.D., President and CEO of Osiris Therapeutics.

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New Zealand's Living Cell Technologies (ASX:LCT, OTCQX: LVCLY) has reported some interim results from its Russian clinical trial of its DIABECELL® implants for insulin dependent diabetes showing signs of sustained benefit. DIABECELL® is LCT's encapsulated porcine insulin-producing cell product designed for the treatment of type 1 diabetes without the use of immunosuppressive drugs.

A total of seven patients have received DIABECELL® implants, five of whom have had two low dose (5,000 islet equivalents (IEQs) per kg body weight) implants at least six months apart. There have been no remarkable adverse events attributed to double implants. Two patients have received a single higher dose (10,000 IEQs/kg) with no safety concerns to date. Therapeutic benefits have also been observed and are described in the update sent to me but not yet available on the company's website.

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Some of my readers and those who listen to my talks aren't fans of the fact I continue to report on and include 'stem cell tourism' companies in my analysis of the cell therapy sector. I understand the reservations and the fact I include them should not be considered an endorsement. My take is that these companies are not going away, they are real business, they are conducting cell therapy as I define it (shodddy or not, credible or not, ethical or not) and and what is needed (per ISSCR) is an informed and informative discussion about how to inject some level of quality assessments over these otherwise unregulated companies and therapeutics.

One such company is Regenocyte Therapeutic. Operating out of Florida where they have their offices and a clinic (I believe for pre- and post-procedural assessments and care), Regenocyte is in the business of recruiting mostly US patients with heart disease for stem cell injections at a clinic in the Dominican Republic for a cost of somewhere around $55,000. They collect blood in a standard blood draw, send it to Israel for the isolation and expansion of stem cells, and then ship the product and patient to the clinic for the stem cell injection. Sounds like your average stem cell tourism business so far but Regenocyte is trying to be different.

Firstly, they don't pretend to be trying to cure everything. They don't have a long laundry list of illnesses they treat. Their website says they focus is on treating patients with heart attack damage, chest pain, poor circulation, leg pain and heart failure. A November press release listed the diseases they address as including congestive heart failure, cardiomyopathy, peripheral artery disease, coronary artery disease, kidney disease, ischemic heart disease, pulmonary disease and early senile dementia.

This is still a long list but largely cardio-vascular in nature and certainly not nearly as long or diverse as many of these clinics advertise. Having said that, they are not unfamiliar with the kinds of promotions and claims that are the trademark of similar clinics. The leading spokesperson, Dr. Zannos G. Grekos, MD, FAAP, recently boldly stated "we are more than doubling cardiac patients' ejection fraction, improving kidney and pulmonary function, saving limbs from amputation by creating new circulation pathways and most recently reversing the life-threatening effects of metabolic heart disease". Not wanting to stop there he then also announced upcoming plans to treat several neurologically based diseases and macular degeneration.

Secondly, Regenocyte is actively looking for a US manufacturer that will produce their cell product in compliance with FDA's rules governing domestic manufacture and export of their class of product.

Thirdly, they are doing at least some long-term follow-up of patients. “We’ve now treated close to 100 patients with their own stem cells and seen an average 22 point increase in ejection fraction (EF) with a significant improvement in heart failure classification - typically from a Class IV to a Class II status in less than 180 days," Grekos states in a press release this week. The cardiomyopathy treatment study, the first six months of which was published December 2008 in Anti-Aging Medical News, follows patients through one year post-treatment with autologous adult stem cells. Grekos and his team measured patients’ heart function by cardiac nuclear scans, PET scans, and echocardiographs.

Finally, the newly published ISSCR Guidelines has given such clinics a potential stamp of legitimacy. Paul Schwartz, Chief Operations Officer says “The patients’ safety comes first,” he explains. “We adhere strictly to ISSCR (International Society for Stem Cell Research) and WHO (World Health Organization) guidelines...”.

COMMERCIAL

Tissue Genesis, Inc announced they have been awarded a $3.62 million contract from the U.S. Department of Defense to continue its research and development activities focused on additional treatment options for those suffering from Peripheral Vascular Disease (PVD). PVD is a circulation disorder affecting blood vessels outside of the heart, including vessels supplying the hands, feet and legs, which can cause severe pain.

With the grant, Tissue Genesis will explore transplanting Adipose (fat) derived Stromal Cells (ASCs), isolated from a patient’s own fat using the Tissue Genesis Cell Isolation System, directly into tissues damaged by a low blood supply. This is expected to increase circulation and relieve symptoms of PVD. An improvement in circulation is directed at preventing disease progression, which left untreated ultimately results in 130,000 amputations annually.

According to Anton C. Krucky, President and Chief Executive Officer of Tissue Genesis, the Department has now awarded the company nearly $24 million to research and develop autologous, adipose derived regenerative medical therapies.

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Cord Blood Registry, a services company in the collection and preservation of newborn stem cells from umbilical cord blood, announced the company exceeded $100 million in annual revenue for 2008 – an increase of 28 percent over 2007. In addition, the company surpassed 250,000 total cord blood units in storage, which represents a 26 percent growth rate for 2008. The company also announced that it released its 100th cord blood unit for medical use, a milestone attesting to the rapidly increasing use of a child’s own newborn stem cells (also called autologous use) for medical therapies to help repair damaged tissue and regenerate healthy cells.

In 2008, the company released one cord blood unit every other week for medical use. To date in 2009, the company has released more than two units per week for medical use. The majority of units released – more than 80 percent – have been used to treat the child from whom they were collected. CBR CEO stated that they expect to release more units for medical use this year than they have released in the previous 12 years.

CBR also announced that it is in discussions with three leading medical institutions to launch a clinical study that will evaluate the use of a child’s own newborn stem cells to treat hearing loss caused by an accident or severe illness. The research will be facilitated and coordinated by The CBR Center for Regenerative Medicine which is currently screening potential candidates for the study.

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Hongkong's Cordlife and Switzerland's BioSafe SA, have announced they have brought the Sepax automated cord-blood processing system to Hong Kong. Sepax is reported to harvest significantly higher numbers of stem cells from cord blood. To date, over 400,000 cord-blood units in 40 countries have been processed using Sepax. The Swiss-made system is also accredited with health ministries worldwide, including those of Japan, the European Union, Canada and Australia.

RESOURCES & EVENTS

NLHBLI has issued a new RFP for PACT centers and administrative office entitled "Cell Processing Facilities in support of the NHLBI Production Assistance for Cellular Therapies (PACT) Program and Support of NHLBI Translational Research in Cell Therapies." The period of performance is for five years beginning on or around November 2, 2009.

Looks like they are wanting to expand to 6 centers in total. I can't imagine the 3 existing centers - University of Minnesota 's Molecular and Cellular Therapeutics facility (MMCT), Baylor College of Medicine's Center for Cell and Gene Therapy (CAGT), and the University of Pittsburgh's Cancer Institute (UPCI) - not getting renewed. What will be interesting is to see who applies and who they choose for the other 3. Will there be any "corporate" service companies that apply and/or are selected?

What's interesting is the fact this is being renewed despite my understanding that at least initially they had difficulty finding ways to spend their money under their mandate as it was initially conceived. This is in part, I believe, why PACT resorted to spending their money on educational type activities. Not that they weren't needed and certainly the identification of that need was also, I suspect, part of their motivation to steer in this direction. Still, according to their most recent newsletter, as of December 2008, PACT had received over 655 application requests for the manufacturing of cell therapy products and while this resulted in over 180 cell products have been administered to patients, it was only from 14 approved projects.

While we're on the subject, one of the useful non-manufacturing outputs from PACT is an abridged list of commercially available cytokines and antibodies. This is not purported to be an exhaustive list but if you see changes you think should be made, let me know - I'll collect your input and forward it on to them.

For those interested, PACT also has a list of cell therapy facility/process/compliance-related SOP's which are available upon request.

*

ISCT is hosting a two-part validation webinar:

• (Part 1): Validation and Qualification of Equipment and Reagents. Wednesday, February 18, 2009,12pm - 1pm EST. Speakers:Lizabeth Cardwell MT(ASCP), RAC, MBA, Principle Consultant, Compliance Consulting, WA; Karen Edward, BS, Advanced Cell and Gene Therapy, NY
  

• (Part 2): Validation of Processes: Retrospective and Prospective. Wednesday, March 25, 2009,12pm - 1pm EST
  

Sign-off...

So that's the shape I saw the biz of cell therapy taking this week. Hope you got something useful...

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Cell Therapy 2009. San Diego. May 3-6.
Attend. Exhibit. Sponsor. Submit your abstract (Deadline: February 200
http://www.celltherapy.org

I'll see you there, right?

*

p.s. Ok I didn't actually buy a bus ad. I cheated. I used the free online bus ad generator :)

Regenexx vs the FDA 2009

Last year I blogged a couple times about Dr. Christopher "the renegade" Centeno from Regenerative Sciences, Inc (aka "Regenexx"). He's in Colorado collecting, growing, and re-administering stem cells for now a growing list of orthopedic-related conditions.

As previously discussed on this blog, FDA CBER's Mary Malarkey sent a warning letter in July 2008 to Dr. Christopher J. Centeno, Medical Director of Regenerative Sciences, Inc (RSI), doing business as Regenexx. The company responded on its website that they do not fall under FDA jurisdiction. One of the reasons cited is that their entire procedure occurs within the state ergo no interstate commerce ergo no federal jurisdiction.

The good doctor (aka @stemcelldoc on Twitter) is not only rapidly expanding the indications for which he'll pump you up with stem cells, he is really ramping up his marketing. He is actively promoting his services on the internet (blogging, a Twitter stream, etc) encouraging people to come from all over god's green earth to visit Colorado and get shot up with a dose of their own stem cells.

Now I know that archaic legal paradigms weren't designed for this new-fangled world but according to a good ole fashioned sniff test many would say that smells a lot like interstate commerce to them.

This is not a critique of the Regenexx therapy, Dr. Centeno, or the company. I'm not saying the Regenexx therapy doesn't work. I'm betting it does. I'm not saying I wouldn't be tempted to go if I had joint problems. I likely would. I'm not saying what they're doing is wrong or even illegal - sometimes it takes a gutsy cowboy/girl or two to change the rules for good. BUT if the FDA lets this happen in Colorado it seems to me a slippery slope to letting all autologous cell therapies go unregulated. And I don't see that happening any time soon.

Rumor has it Regenexx is planning to open a new clinic in Florida. There's the slope in clear sight.

On other fronts, there have been reports of the Regenexx therapy being reimbursed by at least one insurer. Aside from the FDA, this is quickly gaining all the hallmarks of a legitimate medical procedure. As of November, they had performed 250 procedures.

In September last year Dr. Centeno posted on an online discussion board:, "To set the record straight, we have been working with regulatory council for 3 years on our needle based, surgical procedure. We have responded to the FDA unititled [sp]letter and we believe we have answered all of their questions. This is a surgical procedure and not a new biologic drug. We have been communicating with the FDA and they have had no response, so we assume that we have answered their questions."

The FDA may not have any more questions but unfortunately I doubt that ends the issue.

Interstate commerce aside, Regenexx appears to be manufacturing a biological therapeutic. While they appear to have taken references to cell expansion or manipulation off their website, according to a recent blogger allegedly quoting from a letter from the company, the stem cells are collected, expanded (at minimum) and reinjected. The letter apparently stated: "The procedure involves drawing our patient’s blood and bone marrow, growing their stem cells in our laboratory for approximately 3 weeks and then injecting the stem cells into the affected joint".

If this is true, it seems to me this is not just a doctor doing his doctor thing and the big, bad FDA should let a doc be a doc. This would be a doctor manufacturing a biologic without any of the manufacturing controls created by regulatory agencies and industry to keep such things safe - safe, for instance, from contamination.

If there are no such controls in place god only knows what kind of back-alley operations might come to town selling stem cells from basement labs. It is not far-fetched. If this is allowed to continue, other docs will get in this business. Some will decide they just want to run the clinic not grow the cells. They outsource that to company X which is being run by some half-baked science dropout who decided this is probly better money than making meth so let's start a stem cell grow-op! Ok, that's the extreme but you see my point.

I've got a lot of sympathy for people who push against the rules. I believe Dr. Centeno and his company are doing what they believe is right and I'm sure they are doing everything they can to ensure their product is safe and efficacious. I also believe that in years to come we may well be comfortable enough with these types of products that this may well be as commonplace as Dr. Centeno would have it but I don't think it will be in his lifetime. At least not in the US. I kinda hope I'm wrong.

We can't simply let the market decide which therapies will succeed. We need a minimum level of safety assurance and oversight by an agency like the FDA and without any controls how long is it before someone perhaps not as diligent or trained as Dr. Centeno makes a product that does more harm than good?

I think the FDA is building its case and a showdown is on it's way to Denver-town.

Cell therapy is not the practice of medicine

I have several doctor friends who in the early days of cell therapy years ago argued that autologous cell therapies should be considered the practice of medicine - like stem cell transplants - and not require regulatory approval like drugs or devices. Indeed some of the motivation for the creation of industry self-accreditation bodies like FACT was to attempt to convince regulatory agencies that cell therapy products were best regulated by medical industry bodies. The FDA and other regulatory agencies were engaged in this discussion - they heard, they listened...and in large part they disagreed. My doctor friends came to grips with that reality and worked with the FDA to help create a regulatory framework that they now work within.

Even under the strictest regulatory frameworks there are some types of products which do not require formal approval. This blog will not be an overview of the regulatory distinctions between - for instance - s.351 and s.361 products (per FDA) but suffice it to say the differences between the products which do and do not require formal approval are, by now, fairly well defined in both US and Europe (albeit the latter only more recently). Furthermore, the regulatory agencies are eager to engage in dialogue with anyone who has questions about the proper regulatory pathway for their product.

And yet...there are those even now in the US and Europe who attempt to skirt the regulatory framework by conducting unauthorized and/or non-compliant clinical research and/or offering for sale commercial products without regulatory approval despite them falling clearly under the rubric of the regulatory requirements that such products be approved for such purposes.

It's one thing to be offering clinical products in unregulated markets that would would be or are regulated in other markets. I've previously opined here about the medical tourism industry and the issues it raises. But trying to conduct clinical research or sell clinical therapies that are not approved, in markets where there are clear rules governing the authorization to do so? Really?

Regrettably, yes. Two recent examples are described below. I'm not here to cast aspersions, don't want to spark any skirmishes, and certainly have no basis for suggesting impropriety on the part of those involved in these examples. I refer to these examples because they are recent, part of the public record, and, in my opinion, exemplify actions which should justifiably be called out and discouraged (if not penalized).

1. The first example comes out of Europe as described in recent reports in Science, MedPage Today, etc where the Lancet recently retracts a published article stating "... the editors rejected Dr. Strasser's assertion that products of tissue engineering are not medical products and therefore not subject to the Good Clinical Practice requirements."

Following is the report from MedPage Today (5 Sept 2008) :


Lancet Retratct Article on Incontinence Cell Therapy - Free Legal Forms

2. The second example comes from the US. Below is a copy of a recent letter sent to Regenerative Sciences, Inc (doing business as Regenexx) by the FDA .


FDA Warning Letter to Regenexx (Regenerative Sciences Inc - RSI) - Free Legal Forms

There are only three possible explanations I can come up with for why anyone would act as these two teams of people have done in clear contravention of the guidelines regulating their actions: (a) they simply don't understand, (b) they are looking to wage a fight or make a point, and/or (c) they believe their license to practice medicine supersedes regulatory authority (an argument long-ago tried, tested, and proven a loser). None of those reasons are justifiable in the circumstances.


In some instances, those who push the envelope help to shift the paradigm and improve the system they buck against. Even civil disobedience can - at least in retrospect - be occasionally justified if not even heralded as the impetus for positive change. This is not that.

This is playing with people's lives in clear contravention of the rules. That's not to say the FDA always has it right or that there are not issues to discuss or changes to make. The fact that neither of these treatments appear to pose any real risk to patient safety is certainly part of the argument for relaxed regulatory controls - I understand. But does that justify flagrant contravention of the guidelines as they exist using patients as pawns in the argument?

There are other ways to make this case. Go to a jurisdiction where the treatment is permitted, employ patient groups to lobby or litigate, engage industry and FDA in discussions to affect change in the regulatory regime.

Dear Doctor. The fact these therapies may be relatively harmless is no excuse for acting outside the regulatory framework and guidelines created to protect those people you're treating - agree with it or not, like it or not. Thanks.

--Lee