Category Archives: Regenerative Medicine
Are some cell counts too good to be true? Why some companies’ product data may mislead.
Cell therapies present unique challenges when complying with this paradigm for several reasons only two of which I will mention here. Firstly, it is not possible to achieve the level of product purification as one might with other therapeutic products. Secondly, the product characterization is at a cellular rather than molecular level.
Autologous cell therapies present another set of unique challenge in this paradigm because of the notable patient-to-patient variability where the patient is also the donor of the raw material. This often means there is a wider tolerance of heterogeneity in the product but it still must be within what has been proven to the regulatory agency as a safe and effective range.
In cases where an autologous cell therapy is centrally manufactured, they are most often subjected to product release testing similar to that described above. One notable difference, particularly for fresh products, is that the products may be shipped to the clinic and even administered before the full panel of test results are obtained. This wold be considered highly unusual (if ever acceptable) with other types of products but is tolerated because of the time-sensitivity of these products and their high safety profile.
In the case of autologous cell therapy products produced at the bedside there is often not the same kind of product release discipline. Often the regulatory agencies deal with the product consistency and specification compliance issue by ensuring that the cell processing device used point-of-care is validated to ensure the cellular product output is always within a specified range shown to be clinically safe and effective.
The Varying Degree of Product Characterization/Specification of Autologous GTP Cell Therapy Products
However - and now I get to the point of this blog post - for cell-based products, procedures and/or devices/kits which are not mandated to be formally approved by a regulatory agency before they can be commercially marketed, there is no product specification rigor. Compliance with the Good Tissue Practice regulations and guidance is deemed to ensure safety. In the United States, cell-based products which are deemed to be "minimally manipulated" and intended for "homologous use" are typically allowed to go straight to market with no formal approval. Safety and clinical data is not required but is practically necessary to support physician adoption and, where applicable, reimbursement.
This means that for these products there is a great deal of variability in terms of how much rigor companies apply in characterizing their product and then ensuring that each batch complies with the specifications they themselves have determined to be safe and effective. Again, where such products are manufactured in a centralized facility the likelihood of some release testing is greater. However, those companies relying on a point-of-care processing kit or device business model that has not been deemed to require formal market approval, rarely (if ever) include product release testing.
The common criticism of these companies is that they simply do not know what they are injecting into patients because of the combination of the patient-to-patient donor variability, the lack of any disciplined product characterization or dosing studies, and the absence of any product release testing.
This criticism is not equally levied at all autologous GTP products or companies - even those relying on point-of-care processing. Of course some companies care and do a lot to try to ensure their product is well-characterized and that each batch complies with product specifications. This may involve the use of product release tests but can also involve the combination of pre-market research into the product characterization, safety, and dosing along with validation of the device/kit output. In this way a company can say that within a very small margin, the output will be within the product specifications the company knows is safe and efficacious.
However, in a rush to get their device/kit to market some companies appear to care very little about the cell product characterization, validation of the output of their device/kit, or tying this data to optimal dose.
More concerning are those companies that appear to provide such data but it is wrong or meaningless. What follows appears to potentially be a case study of precisely this problem.
The INCELL Study
This week I came across a fascinating white paper from Incell Corporation analyzing the output of adipose tissue processing kits of MediVet-America apparently demonstrating the inaccuracy of their cell counts (a common type of cell therapy product characterization) and calling into the question the cell count claims of Intellicell Biosciences (New York, NY) and Adistem (Hong Kong).
At the heart of the critique is the claim that the cell counting (product characterization) techniques employed by these companies counts as cells things (namely acellular micelles) which are not cells.
I encourage you to read the white paper in its entirety. They corresponding author told me to watch for one or more papers which they are preparing for submission to peer-reviewed publications shortly. Presumably these will rely on a larger data set and perhaps test other methodologies or technologies.
For the purposes of this blog, I've pulled what I believe are the most salient excerpts below:
Intrigued by the high cell numbers (5 to 20 million cells/gram) reported by kit/device manufacturers such as MediVet-America (Lexington, KY), Intellicell Biosciences (New York, NY), and Adistem, Ltd. (Hong Kong) in adipose stem cell therapy compared to other methods (e.g.,
Chung,Vidal, and Yoshimura), INCELL staff conducted a research study to investigate the high apparent yield of stem cells. This initial work was focused on SVF cells from the MediVet Kit, which is marketed to isolate adiposederived canine SVF and stem cells.
The cell yields reported for the Medivet Kits are five to more than ten times higher than the yields routinely obtained by INCELL from freshly harvested human or animal adipose tissue using our adipose tissue processing methods. These yields are also tenfold or higher than those reported in the literature by most academic researchers (Chung-canine, Vidal–equine, Yoshimura–human). Since these cell counts are used to support stem cell dosing recommendations and cell banking, it is important to better understand why the cell numbers are higher.
...
A comparative analytical study of three dog donors of adipose tissue was designed to evaluate the cell yields using the MediVet Kit as an example of this class of isolation system. All kit procedures were followed as per the instructions provided. A brief overview of the different cell counting methods used, and the resultant cell counts, observations and explanations of the results observed, are described below
....
This study shows that incorrect counting of adipose derived SVF cells and the subset of regenerative stem cells can subsequently result in inaccurate dosing, both in direct therapeutic applications and in cryostorage of cells for future use. The DAPI-hemocytometer cell count (manual) was considered the most accurate, but there are various sources of technical difficulties that can lead to incorrect cell numbers. The nature of adipose tissue itself with variability in dissociation by enzymatic digestion can all contribute to the outcomes. Fat tissue has a propensity to form acellular micelles and oils upon tissue disruption. Processing methods or reagents (e.g., Solution E or lecithins) can generate micelles that may be erroneously counted as cells. Autofluorescence and dye trapping or uptake by the micelles can lead to very high inaccurate cell counts when automated cell counting is used.
In this study the most inaccurate counting came from the Cellometer. When used according to kitrecommended guidelines and on-site training provided by Nexelcom for counting cells by the MediVet procedure, the Cellometer overstated the DAPI-hemocytometer cell count by up to 20X or more. The Coulter Counter protocols also led to incorrect, high cell numbers. Although the cell counts were still a bit high, the authors recommend the NucleoCounter, or similar equipment, as more acceptable for automated counting. The manual hemocytometer-DAPI method is the most accurate, but requires a highly experienced cell biologist or technician to make accurate counts and is not suitable for routine clinical use....Other companies also have claims of very high cell numbers when their processes are used. Adistem, like MediVet, states they add an emulsifying agent to their kits to assist in cell release, and they also use a light activation system. Their kits were not tested in this study but it is possible that the high cell numbers reported by Adistem are also incorrect and result from the same problems highlighted in this paper for the MediVet procedure. Ultrasonic energy, which is commonly used to manufacture micellular liposome structures and to disrupt and lyse cells, is another potentially problematic procedure for counting and verifying viable, regenerative cells. Intellicell 3uses ultrasonic energy to release cells from adipose tissue, and it is possible that resultant micelles or cell fragments contribute to the higher than expected cell numbers. This assumption could be verified with additional studies.
In summary, the authors caution that great care must be taken when using kits and automated cell counting for stem cell dosing and cryobanking of cells intended for clinical use. Overestimated cell numbers would be a major confounding source of variation when efficacy of stem cells injected are compared as doses based on cell number and when cryostored cells are aliquoted for use based onspecific cell numbers as a treatment dose. Hopefully, this study will lead to more reproducible counting and processing methods being reported in the literature, more inter-study comparability of cell doses to clinical outcomes, more industry diligence to support claims, and more accurate counting for dosing stem cell therapies to patients....
Chung D, Hayashi K, Toupadakis A, et al. Osteogenic proliferation and differentiation of canine bone marrow and adipose tissue derived mesenchymal stromal cells and the influence of hypoxia. Res Vet Sci, 2010; 92(1):66-75. Vidal MA, Kilroy GE, Lopez MJ, Johnson JR, Moore RM, Gimble JM. Characterization of equine adipose tissue-derived stromal cells: adipogenic and osteogenic capacity and comparison with bone marrow-derived mesenchymal stromal cells. Vet Surg, 2007; 36:613–622. Yoshimura K, Shigeura T, Matsumoto D, et al: Characterization of freshly isolated and cultured cells derived from the fatty and fluid portions of liposuction aspirate. J Cell Phys, 2006; 205:64-76.
The cost of clinical trial data bias/loss, FDA’s new job and the need for bold leadership.
The scandal of clinical trial data loss is eroding the fundamentals of evidence-based research and clinical medicine.
Before you right this post off as the stuff of conspiracy theories, fear-mongering, and 'alternative world views' consider that this view is shared by the likes of the FDA, the International Committee of Medical Journal Editors, the Cochrane Collaboration, and researchers at institutions like Johns Hopkins School of Medicine.
Here's the underlying premise as succinctly described by author Ben Goldacre:
"Drugs are tested by the people who manufacture them, in poorly designed trials, on hopelessly small numbers of weird, unrepresentative patients, and analysed using techniques that are flawed by design, in such a way that they exaggerate the benefits of treatments. Unsurprisingly, these trials tend to produce results that favour the manufacturer.
When trials throw up results that companies don't like, they are perfectly entitled to hide them from doctors and patients, so we only ever see a distorted picture of any drug's true effects. Regulators see most of the trial data, but only from early on in a drug's life, and even then they don't give this data to doctors or patients, or even to other parts of government. This distorted evidence is then communicated and applied in a distorted fashion."
Authors M. Todwin and J. Abramson summarize it thusly:
"Trials with positive results generally are published more frequently than studies that conclude that a new drug poses greater risks or is no more effective than standard therapy or a placebo. Furthermore, some articles may distort trial findings by omitting important data or by modifying prespecified outcome measures. Lack of access to detailed information about clinical trials can undermine the integrity of medical knowledge."
Here is a great list of very recent resources that may convince you of the merits of this concern:
- What doctors don't know about the drugs they prescribe (2012: TED video)
- The drugs don't work: a modern medical scandal (2012: The Guardian)
- Clinical Trial Data as a Public Good (2012: JAMA [subscription req'd])
- Registering Clinical Trial Results. The Next Step (2010: JAMA [subscription req'd])
- The Imperative to Share Clinical Study Reports: Recommendations from the Tamiflu Experience (2012: Plos Medicine)
Cell Therapy’s Got Talent Technology Showcase – A Call for Cell Therapy Manufacturing Technology Presentations
in collaboration with:
In an effort to showcase the latest technologies driving the production of cell therapies, the Cell Therapy Group and Informa Life Sciences are proud to announce the introduction of the "Technology Showcase" session and award to be held in conjunction with Informa's Cell Therapy Manufacturing conference to be held 30 November to 1 December 2011 in Brussels Belgium.
Having held the same conference last year in London, Informa is committed to building on the success of last year's event by continuing to create a meaningful European forum for the issues related to the clinical and particularly commercial-scale production of cell-based therapies.
The Technology Showcase session, taking place on the main agenda, will feature 6 x 10 minute presentations from innovative companies developing cutting-edge technologies in the field of cell therapy manufacturing, and is particularly relevant to SME and academic groups with limited marketing resources.
All presentations will be reviewed by the Scientific Advisory Board with the winner announced at the end of the session. Exposure on BioProcess International's website is also included.
Technologies we'd like to promote include:
- Manufacturing systems including bioreactor technologies
- Cell harvest/collection technologies
- Cell storage/logistics technologies
- Clinical cell delivery and/or other point-of-care technologies
- Automation technologies
- Cell separation system
- Cell process devices
- Innovative reagents, scaffolds, matrices, and other “ancillary” tools
- Technologies to close currently open systems
- Suspension-based production systems
- Disposable technologies
How to apply:
To apply to present companies must submit an abstract (<300 words) to daniel.barry@informa.com and lbuckler@celltherapygroup.com outlining the product or service to be presented and why it is a critical technology related to cell therapy manufacturing.
The deadline for applications is SEPTEMBER 15 2011 - Priority given to early submissions
The cost of taking part in the Technology Showcase is £2,700 which includes the following benefits:
- 1 x 2-day conference pass (normal price £1,599)
- 10-minute podium presentation within main conference room
- 1 poster display in the Exhibition Hall
- Marketing - company logo displayed on website and event guide
- Exposure in BPI Magazine
Terms and conditions:
To be eligible the product or service to be presented must be:
- On the market for no less than 2 years or expected to be on the market no later than Q4 2012
- Appropriate for, applicable to, and compliant with clinical-grade manufacturing requirements (technologies only available for research use will not be considered)
Plus...
- The company must have no more than 15 employees
- The company has been running for no more than 5 years, and
- The company generates annual revenue of no more than $5m
For further information please contact: daniel.barry@informa.com or lbuckler@celltherapygroup.com
Cell Therapy & Regenerative Medicine Domains Available
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Please pardon the crass commercial nature of this post. I try to keep self-promotion to a minimum here but I'm looking to unload a number of domains I have the related to cell therapy and regenerative medicine and thought this might be the easiest way to get the word out. Let me know if you are interested in any of the following:
anticyte.com*
biocellutions.com***
.
cardiacregenerativemedicine.com*
cardiacregenmed.com*
cardiactissuerepair.com*
.
cellexpertsolutions.com**
.
celltherapyalliance.com*
celltherapyassays.com***
celltherapycellutions.com****
celltherapycompany.com****
celltherapyconsortium.com*
celltherapydevelopment.com***
celltherapymanufacturing.com****
celltherapymarketing.com*
celltherapypartner.com*
celltherapypatents.com****
celltherapysolution.com***
celltherapystrategies.com***
celltherapysupport.com*
celltheraytech.com**
celltherapytechnologies.com***
celltherapyventures.com***
celltherapyworks.com***
.
cellutionstrategies.com***
.
commerciaizingcelltherapy.com**
commercialisingcelltherapy.com*
commercializingcelltherapies.com**
commercialisingcelltherapies.com*
.
cordbloodshipper.com***
cordbloodshipping.com***
.
developingcelltherapies.com*
.
diagnostacell.com*
diagnostacells.com*
diagnosticstemcells.com**
.
discoverystemcells.com**
.
expertcellutions.com***
.
integratedcelltherapycellutions.com**
integratedcelltherapysolutions.com**
.
ipsbiologics.com**
ipsbiomedical.com**
ipsbioscience.com**
ipsbiosystems.com**
ipsbiotechnologies.com**
ipslifesciences.com**
.
longtailbiomedical.com***
longtailtherapeutics.com***
longtailtherapies.com***
.
personalizedcelltherapy.com***
.
regenerativecellutions.com***
regenerativemedicinepatents.com****
.
stemostics.com**
stemomics.com**
stemonics.com***
.
stemcellcollect.com***
.
strategiccellutions.com**
strategicell.com***
.
thecelltherapycompany.com****
.
totalcelltherapysolution.com***
totalcelltherapysolutions.com***
Funky ones:
cellenterprise.com*
cellsforce.com*
cellsinnovations.com*
cellsmarket.com*
cellspitch.com*
cellsrep.com*
cellstech.com*
cellsventure.com*
iregener8.com**
I have others - some of which are variations of ones listed above (such as with "the" in front) and would be available - some of which I'm still wanting to hold.
_____________________________
* ~$1,500
** ~$5,000
*** ~$10,000
**** ~$20,000
Another > $100M month for companies in the cell therapy space
Allocure kicked off the month with a decent $25M Series B round from new syndicate member Lundbeckfond Ventures, as well as previous investors SV Life Sciences and Novo A/S. Allocure is headed into phase 2 for acute kidney injury with an allogeneic mesenchymal stem cell therapeutic they currently call AC607.
Little-known Canadian-based, Sernova then announced a $3.6M PIPE to fund continued development of its proprietary Cell Pouch System(TM), and, in particular, to fund the upcoming first-in-man clinical trial for patients with diabetes receiving an islet transplant. The application to proceed with this trial is currently under review by Health Canada.
Next up was NeoStem closing a $6.8M public offering for "expanding" their contract manufacturing business, Progenitor Cell Therapy, and "enrolling the PreSERVE AMR-001 Phase 2 clinical trial for preserving heart function after a heart attack".
The biggest deal of the month was a $65M convertible debt financing of China Cord Blood by none other than global powerhouse Kohlberg Kravis Roberts (KKR) through it KKR China Growth Fund L.P., a China-focused investment fund managed by KKR. We believe this is deal is certainly an investment in the future of China's healthcare market potential but that it is bigger than that. We believe a significant driver for this deal may likely have been the opportunity to consolidate this sector globally - to use a significant operation and 'war chest' to fund mergers and acquisitions on both the public and private cord blood banking sector worldwide.
The only classic first-round venture raise this month was a milestone-based $5M Series A by Bay City Capital into Phil Coelho's new company, SynGen, to fund his latest iteration of stem cell processing devices.
Forbion Capital then announced that it was leading a series D round, joined by fellow existing investors TVM Capital, Lumira Capital, Intersouth Partners, Caisse de depot et placement du Quebec, Morningside Group, and Aurora Funds, of $25M into Argos Therapeutics in order to kick them into their phase 3. The hope here is that with some early phase 3 data they may be able to attract the elusive partner they couldn't land with a mere bucket of phase 2 data.
Innovacell landed the only European deal by announcing an 8.3M Euro (~$11M) investment by Buschier, Fides, HYBAG, and Uni Venture. This will be used for the continued clinical development of its cell-therapy (ICES13) for the treatment of stress-urinary incontinence currently in a ph 3 study in several European countries.
ReNeuron announced a private placement also open to existing shareholders that brought in just under $10M (£6.1M) to support their phase 1 trial in stroke and other pre-clinical, clinical, and regulatory milestones.
Finally, the Bio-Matrix Scientific Group, in an apparent ongoing quest to continuously reinvent itself, announced at month's end that they had formed a new subsidiary named Regen BioPharma and that they had raised $20M in a financing commitment from Southridge Partners II to purchase its common stock as required over the term of the agreement at a price set by an agreed formula. This money is said to be dedicated to the acquisition of discovery-stage intellectual property and driving it through to phase 2 trials in an exercise of maximum value creation over a period they claim to be as short as 18-24 months.
..
So in the end, the month saw companies in the space raise just over $170M and even if you back out the stem cell banking deal its still over $100M for cell therapy companies.
Over the 2 months, then, we've seen just over $311M raised through a variety of means by companies at every stage of maturity and for intended purposes ranging from acquisition, consolidation, early stage clinical development, and phase 3 testing.
--Lee
p.s. If you are aware of other deals in the sector this month, let us know and we'll update this accordingly.
Latest Cell Therapy Approval by FDA. Dendreon’s Provenge.
It has been a long-time coming. It has been hyped and scoffed, bet against and hoped for, but now none of that matters. It's here. Dendreon has brought Provenge to market. Here, in the word's of the FDA...
For Immediate Release: April 29, 2010
FDA Approves a Cellular Immunotherapy for Men with Advanced Prostate Cancer
The U.S. Food and Drug Administration today approved Provenge (sipuleucel-T), a new therapy for certain men with advanced prostate cancer that uses their own immune system to fight the disease.
Provenge is indicated for the treatment of asymptomatic or minimally symptomatic prostate cancer that has spread to other parts of the body and is resistant to standard hormone treatment.
Prostate cancer is the second most common type of cancer among men in the United States, behind skin cancer, and usually occurs in older men. In 2009, an estimated 192,000 new cases of prostate cancer were diagnosed and about 27,000 men died from the disease, according to the National Cancer Institute.
“The availability of Provenge provides a new treatment option for men with advanced prostate cancer, who currently have limited effective therapies available,” said Karen Midthun, M.D., acting director of the FDA’s Center for Biologics Evaluation and Research.
Provenge is an autologous cellular immunotherapy, designed to stimulate a patient’s own immune system to respond against the cancer. Each dose of Provenge is manufactured by obtaining a patient’s immune cells from the blood, using a machine in a process known as leukapheresis. To enhance their response against the cancer, the immune cells are then exposed to a protein that is found in most prostate cancers, linked to an immune stimulating substance. After this process, the patient’s own cells are returned to the patient to treat the prostate cancer. Provenge is administered intravenously in a three-dose schedule given at about two-week intervals.
The effectiveness of Provenge was studied in 512 patients with metastatic hormone treatment refractory prostate cancer in a randomized, double-blind, placebo-controlled, multicenter trial, which showed an increase in overall survival of 4.1 months. The median survival for patients receiving Provenge treatments was 25.8 months, as compared to 21.7 months for those who did not receive the treatment.
Almost all of the patients who received Provenge had some type of adverse reaction. Common adverse reactions reported included chills, fatigue, fever, back pain, nausea, joint ache and headache. The majority of adverse reactions were mild or moderate in severity. Serious adverse reactions, reported in approximately one quarter of the patients receiving Provenge, included some acute infusion reactions and stroke. Cerebrovascular events, including hemorrhagic and ischemic strokes, were observed in 3.5 percent of patients in the Provenge group compared with 2.6 percent of patients in the control group.
Provenge is manufactured by Seattle-based Dendreon Corp.
Careers in cell therapy & regenerative medicine
Cell Therapy Blog welcomes 2013
- a post summarizing some of the things we think are watch-worthy in the cell therapy industry in 2013,
- our recap of the money cell therapy and cell-based regenerative medicine companies raised in 2012, and
- us to formalize our position statement on non-compliant cell therapies as discussed in following previous blog posts:
Source:
http://feedproxy.google.com/~r/CellTherapyBlog/~3/ABphTtPOrwo/cell-therapy-blog-welcomes-2013.html
2013 Annual Regenerative Medicine Industry Report
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The Alliance for Regenerative Medicine announced today the release of the 2013 annual regenerative medicine industry report. Here is the announcement in the Wall Street Journal online.
I'm proud to have been a part of putting it together and hope people find it useful. It is available for download on the ARM website here.
In addition to the complete download, ARM will make many of the figures, charts, tables and sections available for members to download and use in their own publications and presentations. Watch for these resources to be announced soon.
Source:
http://feedproxy.google.com/~r/CellTherapyBlog/~3/yFBYKblnudk/2013-annual-regenerative-medicine.html
The Accuracy of Adipose Stem Cell Doses
In August we published a blog post, "Are some cell counts too good to be true? Why some companies' product data may mislead", pointing people to a white paper released by INCELL Corporation. That white paper appears now to have been pulled from their website (we are working to get a copy to make available again) but now they have published a paper providing more detailed data on aspects of their comparative cell count study.
The paper is introduced by the following abstract:
"Cell therapy products derived from adipose tissue have some unique processing issues with regard to obtaining accurate cell counts. This is because processing methods may not only show us the nucleated stromal vascular fraction (SVF) cells but also the micellular and microvesicle particles. This is true for both veterinary and human clinical products, and poses special concerns for in-clinic processing where the cell therapy dose is correlated with cell numbers and other QC data is not especially useful.
In this study, multiple cell counting methods were compared for SVF cell reparation that were derived from canine adipose tissue using commercially-available rocessing kits. The data clearly showed that many non-nucleated particles appear cell-like by size and shape, and can lead to counting errors with automated counters. In addition, certain reagents important to processing can have properties wherein the reagents alone (e.g., lecithin) may be counted as cells. The most accurate cell numbers were from hemocytometer-counting of cells stained with 4´,6-diamidino-2-phenylindole (DAPI) which shows the nuclei in concert with a viability stain such as trypan blue. The data clearly showed that care must be taken when counting cells used as a therapeutic dose."
This is an important issue particularly as it pertains to autologous cell-based treatments produced by point-of-care devices and/or kits. I encourage you to read the paper.
Morrison DG, Hunt DA, Garza I, Johnson RA, Moyer MP*. Counting and Processing Methods Impact Accuracy of Adipose Stem Cell Doses. BioProcess J, 2012; 11(4): 4-17.
* Dr. Moyer is CEO and Chief Science Officer for INCELL Corporation, 12734 Cimarron Path, San Antonio, Texas 78249 USA. http://www.incell.com
Six steps to fighting non-compliant cell therapy treatments. — The stuff of grey shades, spades, ivory towers and (ahem) balls.
Industry-sponsored cardiovascular cell therapies. Some metrics.
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Cell therapies for cardiovascular-related conditions is a closely watched, much studied, oft-discussed, and hotly contested segment of the cell therapy industry.
The data to-date are admittedly confusing. From a clinical perspective, the studies for which we have data have been relatively small involving a mish-mash of indications, endpoints, eligibility criterion, methods and/or route of administration, as well as the time of administration relative to event or disease progression.
Further compounding any interpretation of the data, from a technical perspective, is the fact the products have been widely varied in terms of being autologous vs allogeneic, expanded and not, genetically modified and not, from a plethora of different sources, and utilizing a wide variety of cell types from skelatal myoblasts, cardiomyocytes, mesenchymal stromal cells, mononuclear cells, etc.
All this makes it extremely difficult to draw any conclusions with respect to what's working and what's not. We will not attempt to do so.
All we do below is attempt to give a snapshot of the industry-sponsored cell therapy trials currently ongoing for cardiovascular-related conditions. So here it is:
Commercial:
Pharmicell's Heartcelligram is the only cell therapy to have received regulatory approval for commercial distribution for the treatment of a cardiac-related indication. Heartcelligram is an autologous cell therapy approved in 2011 by the Korean Food and Drug Administration (KFDA) for the treatment of Acute Mycardial Infarction (AMI). The price is reportedly $19,000 and the trial data behind the approval has not yet been published in a peer-reviewed journal.
Phase III or II/III:
There are currently only 3 active and recruiting cardiac-related, industry-sponsored cell therapy trials. Interestingly they all involve autologous products, two involve devices, two involve centralized manufacturing, two involve bone marrow cells as a source, two are only in European clinical sites, and two are targeting ischemic-related conditions.
- Baxter Therapeutics' Auto-CD34+ cells
- phase III trial actively recruiting
- Indication: refractory angina and chronic myocardial ischemia
- Estimated enrollment: 444
- Estimated primary completion: June 2016
- Cytori
- phase II/III trial actively recruiting
- Indication: ST-elevation acute myocardial infarction
- Estimated enrollment: 360
- Estimated primary completion: July 2014
- Miltenyi Biotec
- phase III trial actively recruiting
- Indication: myocardial ischemia or coronary artery disease
- Estimated enrollment: 142
- Estimated primary completion: July 2012
Mesoblast has also announced with its strategic partner, Teva, that they are proceeding with plans to conduct a phase III study of its allogeneic cell therapy product, Revascor, in chronic heart failure. Most anticipate this clinical trial application to be filed sometime in late 2012.
Phase I or II:
There are over 20 active, industry-sponsored earlier-stage trials (phase I, I/II or II) for cardiovascular-related conditions. At least 5 of these are expected to have clinical readouts this year.
Hope this is useful.
Cell Therapy's Got Talent Technology Showcase – A Call for Cell Therapy Manufacturing Technology Presentations
in collaboration with:
In an effort to showcase the latest technologies driving the production of cell therapies, the Cell Therapy Group and Informa Life Sciences are proud to announce the introduction of the "Technology Showcase" session and award to be held in conjunction with Informa's Cell Therapy Manufacturing conference to be held 30 November to 1 December 2011 in Brussels Belgium.
Having held the same conference last year in London, Informa is committed to building on the success of last year's event by continuing to create a meaningful European forum for the issues related to the clinical and particularly commercial-scale production of cell-based therapies.
The Technology Showcase session, taking place on the main agenda, will feature 6 x 10 minute presentations from innovative companies developing cutting-edge technologies in the field of cell therapy manufacturing, and is particularly relevant to SME and academic groups with limited marketing resources.
All presentations will be reviewed by the Scientific Advisory Board with the winner announced at the end of the session. Exposure on BioProcess International's website is also included.
Technologies we'd like to promote include:
- Manufacturing systems including bioreactor technologies
- Cell harvest/collection technologies
- Cell storage/logistics technologies
- Clinical cell delivery and/or other point-of-care technologies
- Automation technologies
- Cell separation system
- Cell process devices
- Innovative reagents, scaffolds, matrices, and other “ancillary” tools
- Technologies to close currently open systems
- Suspension-based production systems
- Disposable technologies
How to apply:
To apply to present companies must submit an abstract (<300 words) to daniel.barry@informa.com and lbuckler@celltherapygroup.com outlining the product or service to be presented and why it is a critical technology related to cell therapy manufacturing.
The deadline for applications is SEPTEMBER 15 2011 - Priority given to early submissions
The cost of taking part in the Technology Showcase is £2,700 which includes the following benefits:
- 1 x 2-day conference pass (normal price £1,599)
- 10-minute podium presentation within main conference room
- 1 poster display in the Exhibition Hall
- Marketing - company logo displayed on website and event guide
- Exposure in BPI Magazine
Terms and conditions:
To be eligible the product or service to be presented must be:
- On the market for no less than 2 years or expected to be on the market no later than Q4 2012
- Appropriate for, applicable to, and compliant with clinical-grade manufacturing requirements (technologies only available for research use will not be considered)
Plus...
- The company must have no more than 15 employees
- The company has been running for no more than 5 years, and
- The company generates annual revenue of no more than $5m
For further information please contact: daniel.barry@informa.com or lbuckler@celltherapygroup.com
CIRM addresses some tough questions. Is it all just glass towers and basic research?
GEN's "Cellular Therapy Wave Finally Cresting". An overview and data set.
Cell Therapy Industry Group Welcomes its 4,000th member
I'm pleased to point out that today the LinkedIn Cell Therapy Industry Group welcomed its 4,000th member today.
The Cell Therapy Industry group was created to serve as a network of those in the cell therapy industry. The group acts as a vehicle for referrals, networking, information, and facilitating collaboration. The group's focus is on the activities of companies in and serving the space.
The group began in July 2008. It took 2.5 years to reach the first 1000 members, 9 mos to reach 2,0000, 6 months to reach 3,000, and 6 months to meet today's 4,000 member mark.
As is typical, there is a very high percentage of passive participants but the group benefits from an avid group of participants who post, share, exchange, and debate on a range of topics ranging from regulatory, clinical, commercial, scientific, manufacturing, financial, and other topics of interest to the group.
As the group has grown I've noted two trends pertaining to the composition of the membership: (a) having tapped out the c-level suite, growth is increasingly coming from down the hierarchy of the corporate food chain and including those in the operational trenches, and (b) a much higher ratio of new members of late is from outside the US, presumably as LinkedIn increasingly penetrates OUS markets.
We strive hard to maintain the quality of the participation by screening each applicant, deleting off-topic posts, moving promotional posts to the "promotions" tab" and encouraging a balance of news-sharing with useful discussion threads.
I'm proud to say the group has become a vibrant and valuable part of the sector due to the hard work and contributions of all involved.
As these kind of virtual networks become exponentially larger and provide different value than the professional societies representing the sector, I will be fascinated to watch if and how this affects how sectors like our interact and how this will impact the traditional value proposition of member-based professional societies.
If you are not a member of the LinkedIn Cell Therapy Industry Group, check it out.
--Lee
Anticipated short-term cell therapy industry clinical milestones
There are other commercial milestones we are monitoring as well as other clinical milestones we expect to see related to cell therapy products in earlier stages of the development pipeline that are not included below.
CellCoTec (http://www.cellcotec.com)
- Having completed a trial in Europe of their device to enable POC production of an autologous chondrocyte cellular product in/with a biodegradable, load-bearing scaffold for the treatment of articular cartilage defects, they have now submitted their CE market application. The CE mark application is under review and they anticipate a response in October.
- This device and the potential emergence of Sanofi's MACI in the European market next year may have an impact on Tigenix (EBR:TIG) most directly.
ERYtech Parma (http://www.erytech.com)
- Their 'pivotal' phase 2/3 trial in Europe of lead product, GRASPA, for the treatment of Acute Lymphoblastic Leukemia (ALL) is scheduled for completion 2H 2012.
GamidaCell (http://www.gamidacell.com)
- Their 'pivotal' phase 2/3 trial in the US, Israel, and Europe of lead product, StemEx, for the treatment of leukemia and lymphoma, in joint development with Teva, completed enrollment in February and is scheduled for completion 2H 2012. They have not been shy about the fact they expect to be in the market in 2013.
Innovacell (http://www.innovacell.com)
- They raised over 8m Euro in April for a phase 3 trial in Europe for their lead product, ICES13, for the treatment of stress-urinary incontinence which was scheduled for a preliminary clinical data readout in Q4 2012 and be ready for market authorization in 2013. Since announcing the capital raise the company has been stone silent and no clinical trial registry has been filed. Status unknown.
Miltenyi Biotec (www.miltenyibiotec.com)
- Their phase 3 trial in Germany of CD133+ cells as an adjunct to CABG surgery for myocardial ischemia or coronary artery disease is scheduled for completion in January.
NovaRx (http://www.novarx.com)
- Their phase 3 trial in US, Europe, and India of their lead product, Lucanix, for the treatment of advanced Non-small Cell Lung Cancer (NSCLC) following front-line chemotherapy is scheduled in clnicaltrials.gov for completion in October but we have learned they expect their next 'interim analysis' in February.
NuVasive (http://www.nuvasive.com)
- They have a series of trials scheduled to complete 2H 2012 intended to provide additional clinical data to support its marketing of Osteocel Plus for the treatment of a growing number of orthopedic applications.
Sanofi's Genzyme (http://www.genzyme.com)
- Having completed their phase 3 trial in Europe of MACI for knee repair (symptomatic articular cartilage defects of the femoral condyle including the trochlea), they expect to file their market authorization application (MAA) in 1H 2013.
Hope that's helpful and gives you a sense some of the late-stage things to watch for in the coming weeks and months.
--Lee
Cell therapy portfolio outperforms major indices year-to-date
On August 10 we created a model portfolio in Google Finance of 29 public companies in the cell therapy sector then we compared how that portfolio was doing against the major indices year-to-date (Since 1 January 2012). See that post here. Bottom line: even though we are still in a relatively bullish market, the CT portfolio was doing better. Significantly better.
CT model portfolio compared to 3 major indices YTD |
- Cell Therapy Portfolio: +24.44%
- Dow Jones: +4.5%
- S+P 500: +6.78%
- Nasdaq: +10.26%
The cost of clinical trial data bias/loss, FDA's new job and the need for bold leadership.
The scandal of clinical trial data loss is eroding the fundamentals of evidence-based research and clinical medicine.
Before you right this post off as the stuff of conspiracy theories, fear-mongering, and 'alternative world views' consider that this view is shared by the likes of the FDA, the International Committee of Medical Journal Editors, the Cochrane Collaboration, and researchers at institutions like Johns Hopkins School of Medicine.
Here's the underlying premise as succinctly described by author Ben Goldacre:
"Drugs are tested by the people who manufacture them, in poorly designed trials, on hopelessly small numbers of weird, unrepresentative patients, and analysed using techniques that are flawed by design, in such a way that they exaggerate the benefits of treatments. Unsurprisingly, these trials tend to produce results that favour the manufacturer.
When trials throw up results that companies don't like, they are perfectly entitled to hide them from doctors and patients, so we only ever see a distorted picture of any drug's true effects. Regulators see most of the trial data, but only from early on in a drug's life, and even then they don't give this data to doctors or patients, or even to other parts of government. This distorted evidence is then communicated and applied in a distorted fashion."
Authors M. Todwin and J. Abramson summarize it thusly:
"Trials with positive results generally are published more frequently than studies that conclude that a new drug poses greater risks or is no more effective than standard therapy or a placebo. Furthermore, some articles may distort trial findings by omitting important data or by modifying prespecified outcome measures. Lack of access to detailed information about clinical trials can undermine the integrity of medical knowledge."
Here is a great list of very recent resources that may convince you of the merits of this concern:
- What doctors don't know about the drugs they prescribe (2012: TED video)
- The drugs don't work: a modern medical scandal (2012: The Guardian)
- Clinical Trial Data as a Public Good (2012: JAMA [subscription req'd])
- Registering Clinical Trial Results. The Next Step (2010: JAMA [subscription req'd])
- The Imperative to Share Clinical Study Reports: Recommendations from the Tamiflu Experience (2012: Plos Medicine)