How many cell therapy products are in development? Simple question, no?

I have touched before on the nomenclature issues related how we 'define' this industry. Is it cell therapy, regenerative medicine, etc? To some it might seem 'merely semantic' but we all know how difficult it is to communicate something that is really not well-defined. To the extent we need to enhance the profile and understanding of this sector in the world outside it, the better we define the industry the easier it is to communicate. Similarly troubling is the lack of good data regarding the size of the industry. How many companies and/or products? What are the revenues? A broader consensus on how to define the industry can only help us in our dialogue with investors, partners, policy-makers, regulators, etc.

There are somewhere between 225 and 325 companies globally with at least one cell therapy on the market or in development (clinical and pre-clinical). On that much there is a fairly general consensus.

But that allows for a fairly wide margin of error and confidence in the data only gets shakier from there. There is little consensus on the companies that are on that list, the types of products they have, or the status of those products. If one draws the circle broader to include regenerative medicine products, tools, and reagents, the number of companies reaches >650 thus exaggerating the lack of clarity.

In previous posts here I've talked about the number of cell therapy products I believe are currently the subject of industry-sponsored clinical trials globally (and this post will address the topic in more detail). I've also addressed the fact that there is a lot of misconception in the industry regarding particularly the number of products in late-stage, industry-sponsored trials. In large part this is because there is a real lack of complete and reliable sources for this kind of data.

One of the oft-cited sources for this kind of information is www.clinicaltrials.gov. I thought I'd put it to the test. Here are the results of my admittedly rudimentary analysis:

If I type in cell therapy (no quotes) as the only search term, I get 14,022 trials in the search results. When I refine the search by selecting only those funded by 'industry', this narrows it down to 3,817. If I refine it further to include the term 'cell' in the 'intervention' field, this narrows it down to 1,827. A % of these do not involve cell therapies.

If I type in "cell therapy" (with quotes) as the search term, I get 132 trials. Almost all these I would define as cell therapy. When I refine this search to include only those funded by 'industry', I get 32.

In another search I looked for currently open studies, employing 'biologic' as the 'intervention', selected 'industry' as the funding source and searched for the phrase "cell therapy" (with quotes). This produced 6 studies all of which are cell therapy studies.

My next search was exactly the same but with "stem cell" (with quotes) as the search phrase. This produced a list of 19 studies including many of the previous nine but also at least 2 studies I would not define as employing a cell-based therapy but rather another type of biologic.

Using all the same search parameters except typing in the words 'cell' and 'therapy' (without quotation marks) in the search field produces 144 results but a high percentage are not what I would define as employing a cell-based therapy but rather other types of biologics (e.g., Rituximab, Campath). Using the search word "cells" produces 169 results but again many are trials of non cell-based biologics.

To test the database using a specific, I typed in 'Amorcyte' into the sponsor search field. No results. I typed it into the 'search term' field and got one trial listing Emory University as the sponsor.

The data is all over the map and rife with problems associated with the lack of auditing control over the integrity of the data going in. If this is, as many believe, the best single public source of clinical trial data for cell therapies, it is at the very least inadequate to get an overall picture of the true number of trials in the industry. If there are better ways to conduct the search, I'm open to critique.

Industry and market reports are another often relied upon source for this kind of data. I have reviewed several of the leading cell therapy industry/market reports currently available. They rarely - if ever - purport to contain exhaustive company or product lists and the lists they do contain are rife with inaccurate and incomplete information in terms of the companies they list or do not list, the types of therapies the listed companies are said to be pursuing, and the indications to which those therapies are intended to apply.

I certainly do not claim 100% accuracy in my database but I claim it be be as exhaustive as any at least in terms of the list of companies (though likely not in its fields of information such as financial data, clinical trial details, etc). Certainly, the database has its weaknesses (e.g., companies from Asia about which I find it notoriously difficult at times to find detailed information). Having said that, here's what I have.

I am currently tracking >700 companies which I define as stakeholders in the cell therapy sector. This includes ~250 therapeutic companies [i] with ~340 cell-based therapeutic products in the market or in some stage of clinical or pre-clinical development [ii]. These products can be roughly broken down into the following stages:
78 Pre-clinical
77 Phase I
89 Phase II
33 Phase III
67 Commercial (previously discussed in this blog <click here>)

Let me pause here momentarily to say that in an upcoming blog I will break down my 'commercial' number with more transparency. I've been criticized for saying there are so many 'products' on the market when a % of them are unapproved products being sold in unregulated markets. This, in some people's minds, is the equivalent of including crack cocaine in an estimate of the size of the pharmaceutical sector. First let me say I love that critique. I understand. I've never said these are good products, approved products, profitable products... or anything about the products. I believe the critique is a little rough because these products are perfectly legal in the countries in which they are sold. You may think high-priced facial creams claiming to make one's skin feel younger are a fraud but you wouldn't discount them from an analysis of the size of the cosmetics industry.

My only criterion for this number has been whether or not a product is a cell therapy that can be bought legally somewhere in the world. Having said that, I will clarify my list and make it more transparent so readers can make their own assessment. Even after I categorize my list and you limit it down to approved products in regulated markets, it's still two or three-fold what most people think there is.

Note that the numbers for categories other than 'commercial' only include 'products' which are in development in jurisdictions which do have an approval process for such trials and/or products.

I'm also working now on categorizing the products in my database by autologous vs allogeneic, strictly cell-based therapies vs. some combination with another intervention (e.g., drug, device, gene-modification, etc), and by indication (e.g, oncology, diabetes, cardiovascular, neuro, immuno, etc). Stay tuned for those results.

I asked Proteus Venture Partners if they would provide me with a snapshot of their dataset to compare against mine. Proteus is putting together a $200-300 million fund focusing exclusively on 'regenerative medicine' products (as they define them). They have been working now for 3+ years with some of the brightest minds in the sector, to define the industry and put together their own proprietary database intended to drive their investment decisions. They break the industry into 5 sub-categories: tissue engineering, cell therapy, aesthetic medicine, supporting tools/devices, regenerative compounds.

Proteus tracks regenerative medicine which is - as they define it - broader then my 'cell therapy' data set. They also track clinical trials versus my 'products'. However this should be almost the same as my 'products' because when a company is testing the same product for two different indications, I count that as two products.

Proteus has been kind enough to share with me - and permit me to share with you - their numbers. They are tracking ~260 companies with ~430 clinical trials (and commercial products) in the 'tissue engineering' and 'cell therapy' categories'. These trials are broken down as follows:

195 Pre-clinical
77 Phase I
23 Phase II
15 Phase III
124 Commercial

Unfortunately you will note significant differences between my numbers and theirs. A number of potential reasons exist why this is likely the case.

As a VC, Proteus is particularly interested in early-stage technologies (pre-clinical) in which it can participate in the first or early stages of funding. They are - I suspect - decreasingly interested as trials/products become later-stage where there is less opportunity for them to participate in value building. My interest is more in those technologies already in clinical trial and I am increasingly interested the closer the trial/product comes to market. Note our complete agreement on the number of Phase I trials/products where our interests are likely the most closely aligned. For this reason, one might be tempted to trust the Proteus numbers on the early end of the scale and my numbers more on the late-stages.

Proteus also includes some academic-sponsored trials in their pre-clinical number while I restrict my database to only those which are industry-sponsored. This may explain a large bulk of the difference in the pre-clinical number.

On the other end of the spectrum, about 80% of the 'commercial' products Proteus reports are 'tissue engineering' products; the remaining 20% are cell therapy products (~25 products). A number of the tissue engineering products, while regenerative medicine products, would not be included in my 'cell therapy' products because they do not involve the use of cells ex vivo as part of the therapeutic product (e.g., a non-cellular scaffold). If one assumes this is true of 1/2 these products then this would mean our numbers of commercial products are about the same.

That leaves us with the significant difference in the phase II and III numbers. One would expect the Proteus numbers to be higher than mine because they track a wider range of products than I track -- but they are lower. As I suggested above, perhaps phase II and III products are of less interest to Proteus so their numbers in these categories are not as comprehensive as mine. Interestingly, however, we agree on roughly the same number of companies overall. Perhaps my data does not capture multiple trials for the same products as accurately as Proteus' data.

While there are some unanswered questions in comparing the data sets, at the very least the numbers give a range which is likely the best studied and most accurate, data-driven set of numbers that are currently available.

Over the course of the past few weeks I have provided analysis on the number of cell therapy products already commercially available (and how that differs from common perception), the number of phase III/pivotal cell therapy trials currently underway (and how that differs from common perception) and here I have discussed the number of products currently in development.

Coming soon will be a commentary on some of the trends I see coming down the pipe for cell therapy. This will be much more of an op-ed type piece. The 'popcorn report' for cell therapy, if you will. More opinion, less data.

Getting back on the data track I will - as promised above - provide more insight into what types of products are on my 'commercial' list. I also hope to bring you sometime later this Quarter a snapshot of how my data on the therapeutics products in development and in the market breaks down by category (autologous vs allogeneic; strictly cell-based therapies vs. some combination with another intervention (e.g., drug, device, gene-modification, etc); and indication (e.g, oncology, diabetes, cardiovascular, neuro, immuno, etc). Stay tuned for those results.

I know that my data, perspective, and analysis is not without its critics but I hope at least it's of use in spawning a discussion where to-date there has been little data and much misinformation.

--Lee

p.s. Happy birthday nephew Eli! :)

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[i] Other estimates typically range from 225 to 300 therapeutic companies. Sources: author’s database; Cell Therapy Pages (Connexon Communications); Proteus Venture Partners; Bionest Partners. Cell therapies and tissue engineering. February 2007; Burger SR. 2004. Cell and Gene Therapy - Challenges and Strategies for an Emerging Industry. Cell and Gene Therapy 5:9-14.

[ii] “Pre-clinical development” is defined to product in development prior to initiation of a phase I trial but not including products in the early research phase.