Dead on arrival – What can we learn from divested cell products?

by Alexey Bersenev on May 21, 2015 · 2 comments

in cell product, RegenMed digest

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Recently I’ve been reading a post on investor’s web-site Seeking Alpha, entitled “Asterias Biotherapeutics’ Stem Cell Program Is Dead On Arrival“. It made me think – Aren’t most (if not all) divested cell products are “dead on arrival”? And if yes, what can we learn from it?

Let’s look at the biggest shots in cell products divestment of the last 3 years:

    Now, I’d like to highlight some common features of these divested products:

    1. They were divested for a reason. The most frequent reason, mentioned in press releases is financial and strategic – too expensive to handle and changing the company’s focus. However, I truly believe that single most important untold reason is therapeutic under-performance.
    2. None of them were stellar therapeutically. Everyone was hoping for dramatic (significant, impressive, nearly curative – pick the right term) therapeutic improvements, but reality was very different.
    3. All of them were sort of pioneering. Read – first generation. Read – obsolete.
    4. All of them have very very long history of development (20+ years for Prochymal and Provenge)
    5. Most of them had a history of bumpy regulatory approval paths (FDA versus Geron/ Osiris/ Dendreon).

    So, there is nothing more important than therapeutic boost! If 3 out 5 of Geron’s trial patients would walk away from wheel chair in couple of months after “magic injection”, investors would “shower them by gold” and company would not drop the program. But none of 5 patients reported notable improvements. In cell therapy today our expectations set so high – we are looking for amazing therapeutic performance! Who in clear mind today would drop potentially curative product candidate with response rate 90% (yes, I’m talking about CART)? But if therapeutic effects are marginal (Provenge) or moderate (Prochymal) or response rate below 50%, companies may divest without looking back.

    If product cannot deliver great therapeutic performance, it should deliver great economics benefit. In other words – save a lot of money performing therapeutically as good as competitor. In order to achieve economics benefit, the cost of manufacturing should be low, logistics should be very simple and therapeutic effect should last very long. This is not the case for divested products, mentioned above. Manufacturing of Provenge is expensive and logistics is very complex. Prochymal required multiple infusions (up to 10 in GVHD), lasting short time.

    The last point, I’d like to make here is rapid obsolescence of pioneering cell products. In the current speed of technological innovations, long-term cell product development will collide with unavoidable obsolescence. Provenge and Prochymal are typical examples of such collision. They were stalled in development and at the moment of arrival they were already obsolete – dead on arrival. So, why “beat a dead horse” and try to resuscitate it? This field is fluid, let it go!

    So, what can we learn from examples of divestment? I’d put a few things for discussion:

    1. In the field with high demand for dramatic therapeutic boost, the products which able to deliver it should be picked and cherished.
    2. In such dynamic highly technological and innovative field as cell therapy, divestment of products is normal.
    3. There are only 2 real significant reasons for divestment of cell products – therapeutic under-performance and unjustified cost.
    4. If you’re spending 10/15+ years for cell product development you’re running into the risk of technological obsolescence.
    5. Frequently, there is no reason to pick up divested products and try to ask “dead horse to race”. Let it go, kill it. Learn from it and develop new amazing product!

    For those of you, who picked up divested products and trying to resuscitate it – good luck guys! I’d not be in your place.

{ 2 comments… read them below or add one }

Logribel May 22, 2015 at 5:16 am

Thanks Alexey, I believe you’re making very good points here.

In my opinion, the key to stem cell success will be to achieve massive production savings (by favoring allogeneic products) while picking very carefully the right indications in which a clear therapeutic benefit exists (i.e. superior to existing treatments). TiGenix’s Cx601 is a good example of this, I believe, and we should have phase 3 results in a few months.

Unfortunately, at the moment, there still seems to be a lasting drive from some stem cell companies to pick generic and very broad indications in which stem cells always fail to demonstrate “spectacular” results. So, those companies end up in seemingly neverending data mining processes (i.e. Prochymal’s Crohn’s disease trials) or resort to questionable post-hoc analyses to dig up “positive trends” (i.e. Athersys’ stroke results), instead of just letting go, indeed.

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Paul Eldridge May 22, 2015 at 7:23 am

Alexey,
You mentioned the long development time for these example cell therapy products in opposition to the risk of technological obsolescence. This is one area that we as workers in the field should highlight in discussion with regulatory agencies. Better ways to need to be found to speed up the flow through the system. This will serve to strengthen the entire community and serve patients.

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