Whom should we blame for the absence of approved stem cell products in US?

by Alexey Bersenev on September 14, 2016 · 1 comment

in regulation

Few months ago I was watching presentations from Bipartisan Policy Center on support of REGROW Act as alternative regulation for cell therapy, proposed to FDA. I was especially intrigued by presentation of Randal Mills – President and CEO of California Institute for Regenerative Medicine (CIRM). Here is a quote that I’d like to discuss today (watch min 7-8):

It is not difficult to conclude that there is some sort of regulatory problem that exists. The current paradigm has been in place for 15 full years, and there is zero (nothing!) on a scoreboard for stem cells. And there is nothing that is close. So, we don’t actually know how long it will ever take, it’s all theoretical at this point. So, we gonna fix that!

To prove that it is not just his imagination, next minute, he referred to a survey of CIRM stakeholders, 70% of which blamed FDA in stalling stem cell therapy development:

Every group, and it was shocking to us, every group listed FDA as a single biggest impediment to development of stem cell therapy. That’s in state of California.

I’d encourage you to whole whole presentation, but one more important thing to mention here is his argument for so-called “on-pathway” (current over-regulation by FDA), which involves by estimates ~15 years and ~$1B investment for development of cell therapeutic (slide 14):

No one has gotten through it, but we’ve had a lot of people had dropped out that race.

You can also read Mills writings here and here. In brief, he as well as CIRM stakeholders, put whole blame for absence of approved stem cell therapeutics in US on FDA – regulatory framework for cells, created by FDA about 15 years ago was promising, as proposed, but it never delivered.

This “let’s blame FDA” position is very different from what I’ve heard on multiple conferences that I’ve attended. Many stakeholder, especially product developers from “compliant industry” claimed that FDA is a partner, but not a barrier. Every developer, who was asked about their experience with FDA said that the Agency was very helpful and engaging since the first day of communication.

I was trying to memorize “stem cell products”, which were “killed” by FDA (to confirmed Mills statement “a lot of people had dropped out that race”), but did not find any example. The only possible candidate was Prochymal – mesenchymal stromal cell-based product, developed by Osiris, which failed few Phase 2/3 trials in several indications. Mills was CEO of Osiris exactly that time. Seem like Mills got frustrated with FDA, which did not like Prochymal’s efficacy data, and, product was eventually divested to another company (Mesoblast). But, to me, Prochymal was not killed by regulators. It was not good product with only moderate efficacy profile in some subsets of patients. Also, I think, developer (Osiris) failed with trials design. Seem like there is no reason to blame FDA here.

Now, let me articulate my opinion. I think, most, if not all stem cell products-candidates were not good in the past 15 years. To me, this is a major reason for absence of approved stem cell products in US. If product will perform exceptionally well in trials, FDA would greatly support it! I may be too naive, but it’s my feeling now. So, I’d respectfully disagree with Dr. Mills and CIRM stakeholders on this. Regulatory uncertainty, to be fair, may also played some role for few developers, but not the major.

I was wondering what other people think of this and, first asked my followers on twitter. Here is result of my brief poll:

2/3 of my followers agree with me – we have to blame developers for bad products, first of all. Some industry professionals voiced their opinions publicly on this. The most recent example is CEO of British company Celirix, who said: “Lack of innovation is the only barrier when it comes to cellular therapies”. I’d also like to note that I saw few surveys on barriers to deliver cell therapeutics to the market and all of them include “regulatory issues” option. If you’re a developer, who answering such survey, would you admit that you’re product suck? When developers answering these survey they usually have no idea how their product will perform in advanced phases of trials and whether design of the trials will be just right.

In the past few years different cell therapy stakeholders were surveyed on barriers to translation. It seem to me, only CIRM survey shows FDA as a single major barrier. For example, industry organization ARM surveyed Biotech companies on investment in regenerative medicine in 2014 and concluded:

The companies surveyed believe regenerative medicine products have the ability to succeed within current regulatory frameworks, but product consistency and lack of standards could be the single greatest barrier to their growth.

Another examples of surveys (more general, on cell products) you can look at here, here and here. Efficacy, funding, manufacturing, cost-effectiveness among with regulatory requirements are all in the complex mix of challenges for commercial translation of cell therapeutics. But remember, efficacy will drive everything! If your product as efficacious as 50-90% in “no option” patients and potentially curative, regulators will love you, tools manufacturers will find a way to make it cost-effective and affordable, investors will shower you with money!

Finally, I’d like to ask you – if you know any examples of great stem cell product candidates, which were “killed” by FDA, please bring it up in discussion! I’d be happy to learn. Obviously, it is not about cells from fat as practice of medicine, but all about commercial cell product-candidates in development.

{ 1 comment… read it below or add one }

Bert September 18, 2016 at 4:31 am

I think TiGenix is the next stem cell phase III on the list in the US or one of the close ones (Cx601 in Perianal Fistulas of Crohn’s Disease). Planed for H1 2017 with BLA filing in 2019. TiGenix already succeeded in the phase III for the EMA filing they did in March. From TiGenix feedback on their interactions with the FDA, we cannot say FDA has been such a barrier, they even agreed to an SPA to set the p-value of the US phase III at 0.05 instead of 0.025 for the European phase III and to have the same primary endpoint !!! By the way,
‘the Type B meeting with FDA confirmed:
•Adequacy of existing non-clinical package to support an IND3 filing
•Acceptability of using data from the ADMIRE-CD trial to support BLA’
So it seems they were mostly supportive more than puting a spoke in their wheels.


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