Katie Thomas at the New York Timesreports that BARDA has dropped considering funding applications for stem cells for COVID-19. The move is part of a larger shift in funding priorities away from lung treatments and toward vaccine development. The decision has puzzled and even angered some stem cell firms and researchers.
BARDA stands for Biomedical Advanced Research and Development Authority. It has become a core decision maker related to funding for COVID-19. The BARDA shift can be found in a few notices such as this one on June 3, but it’s a bit hard to navigate. Here’s the key verbiage on the suspension:
“All contracting related inquiries should be sent to BARDA-BAA@hhs.gov. BARDA suspended AOI 9.3 immunomodulators or therapeutics targeting lung repair, suspended AOI 9.5 Pre-exposure and post-exposure prophylaxis, suspended AOI 11 Ventilators, revised language for AOI 3 Antibacterials (submissions are placed in post COVID-19 review queue), added AOI 7.7.4, and revised language for AOI 9.2, 9.3, 9.5”
The stem cell and other cellular medicine efforts that had hoped to get BARDA funding were within the “mmunomodulators or therapeutics targeting lung repair” area. From Thomas’ article:
“In interviews, six company executives and academic researchers who had begun the application process with BARDA said they had not heard back from the agency, or had been told their research area was not a priority. An executive for one biotech company, who did not want to be named because he did not want to jeopardize future federal contracts, said the company had been in the final stages of negotiating a deal with the agency when it suspended applications. That partnership is now on hold.”
One researcher was Duke’s Joanne Kurtzberg, who has been focusing on cord blood and mesenchymal stroma/stem cells (MSCs) for autism and cerebral. Apparently, she and many others believe that cord blood cells could possibly help COVID-19 too. From NYT:
“It seems that BARDA is shutting the door on that whole area of medicine,” said Dr. Joanne Kurtzberg, a stem cell researcher at Duke University.
She had asked the agency in early April to support a small clinical trial on the use of stem cells in patients with Covid-19 who had acute respiratory distress syndrome and said she had received only an acknowledgment that her proposal had been received.”
Why might BARDA have punted on funding cellular medicines and other approaches to tackling the damaging inflammation and overall immune activity in the lungs? Although I’m fairly skeptical of the stem cell angle, there is a fair amount of enthusiasm in the field for testing therapies based on immune cells and stem cells for COVID-19. Here are some possible challenges.
Cell therapies are generally hard to scale quickly. The cells most often being tested in trials for COVID-19 are relatively slow growing mesenchymal precursor or stem cells. The rate of cell growth directly determines the timeline of how many doses you can produce and it will be severely limited compared to, for example, how much of an anti-viral drug one might be able to chemically manufacture. With cells you also have to worry about keeping them alive, healthy, and free of mutations, as well as issues of whether you freeze your product along the way and then have to thaw it.
Within the context of COVID-19 illness with severe inflammation, how many of the transplanted cells will survive? It can be hard to know what’s going on as the transplanted cells are hard to track. Their survival may also be lower since most often the cells will come from a different person rather than being the patient’s own cells and they will not be matched in the way that organ or bone marrow transplants are. Some stem cells survive even in such an “unmatched” transplant setting, but you can’t count on that.
More broadly I have concerns about the potential efficacy of cells here, as sponsors are focusing on immune modulating functions. In looking at the cell therapies proposed for COVID-19, often times the rationales are relatively weak. Sometimes the products in question were originally intended for some other use such as complications of bone marrow transplants or for cancer treatment, and are being repurposed for COVID.
BARDA concerns on risks and the elusive Goldlocks immunity target?
There mostly just isn’t convincing data to back up devoting tons of resources to this. My past analogy of throwing spaghetti against a wall and hoping something sticks seems apt here. Cellular therapies for COVID-19 are going to have risks as well. For instance you could make the immune system weaker in a negative way or you could make it too strong, exacerbating inflammation and lung tissue death. What’s the sweet spot for a cell therapy tweaking how the immune system works in any particular COVID patient? Who knows.
Big picture of stem cells for COVID-19
We just don’t know if cells are a good approach yet for the novel coronavirus.Is it wise of BARDA to entirely give up on the idea? I don’t know at this point. BARDA has had some political issues during the pandemic. Former head of BARDA, Rick Bright (pictured above), has said he was removed from the post because of conflicting views with the White House, possibly related to hydroxychloroquine.
Hopefully politics wasn’t involved in this latest BARDA move.
It’s not clear how this move might impact biotechs that have been much in the news lately related to FDA-cleared trials for stem cells and other cells for COVID-19, such as Athersys. Just because FDA clears an IND doesn’t mean a trial can be done if there’s not enough funding.