Cell Therapy Industry HiLites 2009-03-27

Here's a big thank you shout out to the growing cadre of great readers, subscribers, and participants in the network of cell therapy colleagues I'm proud to be part of whether it is here on this blog or on our LinkedIn Cell Therapy Industry Group. We're proving cell therapy means business! Keep up the outstanding repartee.

In keeping with the biblical proposition that "nothing new is under the sun", a new physician group as been formed to "oppose FDA's position on adult stem cells". The newly formed "American Stem Cell Therapy Association (ASCTA)" this week posted its manifesto online and issued a press release saying the "organization was formed in response to the Food and Drug Administration's (FDA) recent position that the adult stem cells found in everyone's body are drugs, a position the ASCTA opposes." I'm not sure which move the FDA made recently that would make these docs think this is the FDA's recent position. As I wrote on this blog back in September last year, doctors have been trying to tell the FDA that cell therapy is the "practice of medicine" for years and it hasn't worked. Of course, it will come as no surprise to you that central to this new movement of doctors lobbying for the right to treat patients with their own stem cells however they see fit, is Dr. Chris Centeno of Regenexx and other doctors like Dr. Zannos Grekos who are involved with stem cell treatment clinics marketing to US patients for clinics performing their magic outside the USA.

In a classic case of overstating the point, ASCTA member Dr. Frank Falco states, "The FDA's position against someone using their own stem cells is taking it too far." Of course, saying that is the FDA's position, is taking his point too far but subtleties like that don't get people engaged in a revolution!

Enough of that. On to the news & analysis. It wasn't a great week for cell therapy with Osiris stopping its phase III trial for Chron's and all but that had more to do with the difficulties of designing good clinical trials than it did cell therapy.

FINANCIAL

Intercytex Group Plc (AIM: ICX) announced it is in talks which may lead to an offer for the company. In February, the company said it was reviewing options, including a possible sale or merger, after it stopped work on Cyzact, one of its main products, to preserve cash. The company's product Vavelta has reportedly now treated 120 people in a commercial setting and its ICX-SKN skin graft replacement for burns and acute wounds is fully funded by the US Armed Forces Institute of Regenerative Medicine. Inercytex reported revenues of £17,000 for the year.

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Taiwan is angling to be one of the major biotech hubs of Asia by making biotechnology the country's third major industry in the next 10 years. To that end, it has proposed a $1.76 billion dollar VC fund. The Taiwan government's National Development Fund will have a 40 percent stake in the venture, and the private sector will see to the other 60 percent. The economic development plan also calls for the establishment of a biotech incubation center that will introduce new medicines to existing biotech parks. Taiwan has a strong interest in cell therapies and the country's regulatory authority(the BFDA) is investing heavily in establishing a well-defined regulatory framework for cell, gene,and tissue based products. Unlike Singapore's investment in stem cell research, Taiwan appears to be positioning itself to support later-stage commercial entities already working on translation of research into clinical products.

CLINICAL

And here's the big news of the week. Osiris Therapeutics, Inc. (NASDAQ: OSIR) announced it was stopping its phase III clinical trial of Prochymal for the treatment of acute Crohn’s disease (CD).

The good news? It was not for safety concerns. The decision was made after the trial's final scheduled interim analysis showed that one of the two Prochymal dose arms (they don't know which because that has not yet been unblinded) in one of the two trials in the program had crossed a futility boundary (would not achieve statistical significance) according to the study's DSMB.

Osiris’ phase III CD program consisted of 2 trials, and induction trial (S-603) and a maintenance trial (S-610). The Study-603 “Induction” trial was randomized into three arms, one-high dose Prochymal (400M cells for the 1st two infusions and 200M cells for the next two) , one low-dose Prochymal (200M cells in the 1st two infusions and 100M cells in the next two) and placebo. After 28 days of dosing, patients were evaluated by a subjective evaluation for a reduction in the Crohn’s disease activity index (CDAI). Patients with a 100-point drop in CDAI score according to the self-evaluation were then eligible for re-randomization into the longer-term Study-610 “Maintenance” trial. It is this design that management now believes presented an inducement for patients to "over-report" improvements so as to be eligible to participate in the longer, subsequent trial. This is evidenced, they believe, by the fact that 56% of the participants in the in the S-603 program enrolled in the S-610 program when they would have expected the number to be more around 30 - 40%.

The other pieces of good news to salvage out of the day are (a) Genzyme supports the decision, and (b) the trial had already enrolled 210 of its expected 270 patients. Osiris is going to complete the study as if it were a 210-patient study in hopes that there is significant data from the trial that can not only be used in redesigning subsequent trials but also to bolster Prochymal’s overall safety database. Regarding Genzyme's position, this is certainly reason for them to be disappointed but this saves them milestone payouts in the short-term and they are not on the hook for the additional costs that will be incurred because of the decision so as long as they still believe in the fundamentals of the product, they have no reason to pull out of the relationship now.

Randy Mills spent some time in a webcast on Friday explaining the details of what transpired, the decision, what they theorize went wrong or was wrong with the trial, and where they anticipate going from here. He made it very clear a number of times that there is no reason to believe this will have any impact on the Prochymal trial for GvHD. One of the other things he explained was that Osiris never believed this current phase III program for Crohn's was going to be sufficient to support a BLA. They had always anticipated another phase III trial. What Randy didn't say was whether this decision would mean another one or two trials would be required.

Analyst Jason Napodano is on record stating he believes "it could be a year or so before Osiris can re-initiate the Crohn’s program, which will most likely include two separate phase III trials, one induction and one maintenance, but once initiated the program should enroll quickly given management’s experience from just halted program and the inclusion of several additional new centers that did not participate the first time." Despite the setback he believe the news presents a buying opportunity for Osiris shares which were down as much as 22% in Friday's trading.

He believes "Osiris remains financially sound and should exit 2009 with over $100 million on the books" and expects "Prochymal will be on the market in the U.S. by the end of next year for GvHD". They have a target of $25 per share.

In Friday's investor teleconference, Randy stated he expects the company will be reporting top-line data on the Prochymal trial for steroid-refractory GvHD in 3Q 2009 given that enrollment in that trial is already complete and, based on enrollment rates for the acute GvHD trial, he expects to be reporting data from that trial in the same Quarter.

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Neurotech Pharmaceuticals, Inc. announced that the Company's lead product candidate, NT-501, substantially slowed the loss of vision in a Phase 2 clinical trial in subjects with dry age-related macular degeneration involving geographic atrophy. NT-501 is an intraocular implant that consists of human cells that have been genetically modified to secrete ciliary neurotrophic factor (CNTF) which is delivered directly to the back of the eye in a controlled, continuous basis by means of the Company's proprietary Encapsulated Cell Technology platform, thereby bypassing the blood-retinal barrier. The Phase 2 study is a multi-centered, randomized, double-masked, sham-controlled study of 51 subjects with GA. Patients received either a high or low dose NT-501 implant or a sham treatment in one eye only. The high dose of NT-501 stabilized best corrected visual acuity at 12-months, with 96.3% (p=0.078) of treated-patients losing fewer than three lines of vision, or 15 letters, versus 75% of the patients in the sham-treatment group.

What I find interesting about the study is that five devices from this trial have now been explanted 12 months following implantation and all have been found to have uniformly healthy, viable cells that continue to produce therapeutic levels of CNTF. This is reportedly consistent with data from multiple trials of NT-501 in which, to date, 23 devices have been explanted between 12 and 18 months following implantation and all devices have contained healthy, viable CNTF-producing cells.

The clear implication is that the implanted devices would continue to excrete therapeutic levels of CNTF longer than the 1-year threshold for the study. This is proof-of-principle for Neurotech's Encapsulated Cell Technology platform which may well have sundry other applications.

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Will Dendreon's unblinding and announcement of interim analysis data for Provenge back in October be its final bad decision? Four top statisticians say Dendreon may have compromised the integrity of the trial by putting out the release. They say it was unorthodox for Dendreon to even know such a detailed result, much less to publicize it. The danger: The company, patients or doctors might have changed what they were doing once they knew how the study was going. If the final outcome is only marginally statistically significant, it might be tossed, putting Dendreon and its drug back at square one. The statisticians are left scratching their heads at the data release. "I have no idea what their rationale would have been," says Susan Ellenberg, a statistician at the University of Pennsylvania. "I can't rule out the possibility that they did have a reason I'd be comfortable with, but I can't think what it might be."

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Finally there is some news about a US company treating patients in a clinic outside the US in a way that many would say has hallmarks of scientific credibility. Two years ago DaVinci Biosciences, headquartered in Costa Mesa, California, treated 52 acute and chronic spinal cord injury patients in Ecuador with injections of their own bone marrow-derived stem cells. They conducted follow-up studies and have now published the results for the first 8 patients in issue 17(12) of Cell Transplantation. The follow-up report claims that MRIs have revealed "noticeable morphological changes within the spinal cord after administration of autologous bone marrow derived stem cells." There was no tumor formation, increased pain or deterioration of function following administration of the stem cell treatment. The researchers conclude that the therapy proved safe and effective in improving their quality of life. Although there are plenty of stem cells clinics claiming anecdotal evidence (not published in peer-reviewed journals) of the therapeutic effect of such treatments and there have been numerous studies in animals demonstrating the benefits of stem cell treatment for the treatment of spinal cord injury, this may be the first published study of its kind.

COMMERCIAL

In what is now becoming a trend between large pharma and research institutes, the Salk Institute announced a strategic alliance agreement with Sanofi-Aventis establishing the Sanofi-Aventis Regenerative Medicine Program (SARP). Financial terms of the three- to five-year agreement were not revealed.

Saying that the program was without "restrictive preconditions", the announcement was vague on details about the anticipated nature of the collaboration other than it would sponsor "institute-wide discovery grants in promising research areas that address the organizations’ mutual interests" It was also unclear what types of results or products Sanofi expected to get from the program other than "research retreats and "extended working lab visits". The San Diego Business Journal reports that Sanofi-Aventis will have the option to license any discoveries that result from the collaboration. It's not clear to me how this fits with the deal Salk made last year when it partnered with another French pharmaceutical company, Ipsen, in a deal worth $10 million over five years. It's also not clear to me if this is an investment in cell as therapies or more about cells as tools. We can not necessarily infer the former simply from the "Regenerative Medicine" name put to the program.

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Stratatech Corp. announced that it has launched the StrataTest® human skin model. Composed of both an epidermis and a dermis, the StrataTest® human skin model is said to display the physical, chemical and histological characteristics of native human skin. The tissue is supplied in a 24-well format for consumer product testing, drug discovery and toxicity screening.The StrataTest® human skin model, which is intended for research use only, is manufactured using Stratatech’s proprietary NIKS® human keratinocytes. Stratetech believes the product offers a "superior, cost-effective, in vitro testing skin model that it believe enables better prediction of in vivo biological response for consumer product, drug discovery and other toxicity testing applications.”

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Stepping into a space owned primarily by MaxCyte and Lonza's Amaxa BioSystems, Invitrogen, a division of Life Technologies (NASDAQ:LIFE) announced the launch of it's "Neon Transfection Device", a bench-top device for the delivery of DNA, RNA, and proteins into a wide range of mammalian cell types, especially difficult to transfect cells, such as many types of primary and stem cells. The Neon Transfection Device is reportedly well suited for gene and siRNA delivery into stem cells, features a unique transfection chamber that minimizes cell death, has minimal reagent requirement, and works with many different cell types.

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Progenitor Cell Therapy, LLC (PCT) announced that Lisa Doria-Cavuoto will be joining the company as Vice President of Commercial Cell Therapies, effective April 1, 2009. In this role, she will be responsible for managing the day-to-day business operations of PCT's commercial stem cell processing, storage, and clinical distribution service.

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Former GE Healthcare & Thermogenesis executive, Dan Segal, is heading up a newly minted private cord blood bank in Orange County, California called PacificCord.

RESOURCES, EVENTS, & MISCELLANEA

ISCT has released a call for Late Breaking Abstracts in the following categories:

• Mesenchymal and Tissue Stem Cells
• Hematopoietic Stem Cells
• Gene Therapy
• Immunotherapy and Dendritic Cells
• Cell and Tissue Evaluation
• Lab Practices
• Legal and Regulatory Affairs
• Translational Process Development
  

Deadline for Submissions: April 3, 2009. Notification of Abstract Status: April 10, 2009

Click here to submit.

Sign-off...

I spoke this week to an American-trained plastic surgeon now practicing in Asia. In 2006 he paid (presumably handsomely) to attend a symposium hosted by 3 European "professors" on commercial "cell therapy" techniques that are being sold today in select jurisdictions and which could bring longevity and youthfulness to clients everywhere and, I assume, fame and fortune to the doctors brave enough to sell them. One was "live stem cell therapy" using rabbit fetal cells and the other was "fresh/frozen cell therapy" using cells from sheep embryos (or placenta?). He was so impressed he bought into the program, tried it on himself, his family, and then, convinced it was safe, started to sell it to clients. The good doctor I spoke with was using the sheep product, as many others are doing, and administering them not topically but intra-muscularly for "skin rejuvenation".

Long story short, he is now being prosecuted by his Medical Council for providing non-evidenced based medicines. Here's the rub. This all sound quite ghastly to many of us but there is at least one clinic in Switzerland that has been injecting sheep cells into people for over 50 years without any apparent safety issues and to the endless, anecdotal accolades of clients who claim enhanced youthful visages, energy, sex drive, longevity, etc. What's more, there is an internet site where you can buy sheep placenta capsules and even human placenta injectibles. I won't link to any of these sites because I don't want to give them the web traffic but a quick Google search will lead you to multiple clinics and distributors.

I don't envy the position of regulators. As much as a clear and enforceable regulatory framework is critical to the industry, so is a strong and properly financed regulatory authority. Equally important is that we as an industry be vigilant in protecting the quality of our science, our medicines, and our patient's health. We are not grappling with easy issues here. Perhaps the injection of sheep or rabbit fetal cells are the cure-all they are reported to be but what it they're not and we're injecting them into human for non-life-threatening conditions?

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That's the kind of week its been. Feel better about yourself and tell a friend about the Cell Therapy Blog today! :-)