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.
Rick Bright, former head of BARDA, may have been removed from the post for political reasons.
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.
Scaling, freezing?
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.
Cell Survival?
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.
Rationales?
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.
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14 thoughts on “BARDA drops funding of research into stem cells for COVID-19”
Jeanne Loring
Stop it, everyone. The problem with MSCs is that they are not a defined cell type. Depending on where you get these connective tissue cells, how long and how you culture them, they are all different products. Other cell therapies, including hESC and iPSC-derived cells and CAR-T, require rigorous release criteria. Invest in science instead of marketing, and you’ll do far better. Right now you look too much like hype.
Paul ,
Have you thought about talking to BD for subsetting of T cells during Covid 19 , especially CD 4 activated cells related to MSC stem cells ,,,,CD 4 are lost in severe cases of Covid 19……Another thought ha e you interviewed the CEO Mesoblast? “Researchers and companies are also testing stem cell therapies, which are also believed to dampen the immune system. One company, Mesoblast, is testing its stem cell product in patients with severe Covid-19 as part of a clinical trial supported by an arm of the National Institutes of Health.” NY Time June 19, 2020..
In fact , Mesoblast’s Phase 3 #RandomizedControlledTrial of remestemcel-L in 300 ventilator-dependent patients with moderate to severe #COVID19 ARDS is underway in the US. Patient enrollment is expected to be completed within 3-4 months after the first patient was dosed in May.6, 2020……
Mesoblast’s RCT of remestemcel-L to treat #COVID19 Acute Respiratory Distress Syndrome (ARDS) is enrolling at hospitals across the US: CA, GA, IN, LA, MD, MA, MI, NH, NY, NC, OH, PA, TX, VA.
Complete list of hospitals participating:MSCs in COVID-19 ARDS
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT04371393
Recruitment Status : Recruiting
First Posted : May 1, 2020
Last Update Posted : June 19, 2020
See Contacts and Locations
Sponsor:
Icahn School of Medicine at Mount Sinai
Collaborator:
Mesoblast, Inc.
Information provided by (Responsible Party):
Annetine Gelijns, Icahn School of Medicine at Mount Sinai
Study DetailsTabular ViewNo Results PostedDisclaimerHow to Read a Study Record
Study Description
Go to sections
Brief Summary:
The mortality rate in SARS-CoV-2-related severe ARDS is high despite treatment with antivirals, glucocorticoids, immunoglobulins, and ventilation. Preclinical and clinical evidence indicate that MSCs migrate to the lung and respond to the pro-inflammatory lung environment by releasing anti-inflammatory factors reducing the proliferation of pro-inflammatory cytokines while modulating regulatory T cells and macrophages to promote resolution of inflammation. Therefore, MSCs may have the potential to increase survival in management of COVID-19 induced ARDS.
The primary objective of this phase 3 trial is to evaluate the efficacy and safety of the addition of the mesenchymal stromal cell (MSC) remestemcel-L plus standard of care compared to placebo plus standard of care in patients with acute respiratory distress syndrome (ARDS) due to SARS-CoV-2. The secondary objective is to assess the impact of MSCs on inflammatory biomarkers.
Detailed Description:
This will be a randomized (1:1 ratio), double blind, parallel design, placebo controlled trial. Randomization will be stratified by clinical center and by moderate versus severe ARDS. The study is designed to have three interim analyses for stopping accrual early for efficacy and futility when 30%, 45% and 60% of the 300 patients have reached the primary endpoint using Bayesian predictive probabilities.
Patients will be randomized in a 1:1 allocation to intravenous infusion of MSCs (remestemcel-L) plus standard of care versus placebo plus standard of care for the treatment of COVID-19 related ARDS:
Group 1: 2×10^6 MSC/kg of body weight plus standard of care, administered twice during the first week, with the second infusion at 4 days following the first infusion (± 1 day)
Group 2: Placebo (Plasma-Lyte) plus standard of care, administered twice during the first week, with the second infusion at 4 days following the first infusion (± 1 day) (control)
MSCs and placebo will initially be administered intravenously in the dose defined above at randomization. The rate of infusion may be tailored to the patient’s respiratory status and fluid status, but the duration of infusion should not exceed 60 minutes.
Patients will be followed for 90 days post randomization, with assessment of pulmonary symptoms at 6 and 12 months.
Science must have the fortitude to withstand scrutiny. One can argue it must be scrutinized to be real science. We’ve seen retractions, and money grab, and many things that tarnish the reputation of science. Paul not always right in every post he does, but… the vast majority of concerns he raises are usually legitimate concerns. Sadly science and politics are forced to mingle more than most would like these days (ie the blockade on climate research by the current administration).
Do stem cells hold promise? Yes. Are there bad actors that need to be called out? Absolutely. Have far too many companies tried to jump on the ‘Treat/Cure COVID-19’ bandwagon… probably. Some might be for the right reason, but more than a few are looking for quick money (either profit or just grants/funding). It’s a hard call with the pandemic, how far do you push the ethical limits of quality risk-based medicine?
Paul’s done more research on some of these topics than many who comment. And he’s been willing to concede or update a post when credible information is brought to light. All in all it seems like he’s doing a A-level job with his blog. For this story, it seems more to the point of the politics involved than the science…
@Matt,
Thanks for the feedback and support.
If I’m wrong about stem cells or NK cells, etc. helping COVID-19 patients (and I hope I am) then I’ll be the first to post about it, point out my over-skepticism, and herald the success
In an off the cuff reaction to old news, the author takes is a broad swipe at a basket of unnamed stem cells companies, save one, without doing any actual research. I’d say the article reflects far more poorly upon the author then the stem cell companies discussed.
I had hoped to cover this story the day it broke, but life is busy.
Just curious — are you an investor in one or more of the stem cell/cell therapy companies with trials on COVID-19? Do you have one you think is most promising?
Paul,
With all due respect, If you are going to be writing about Athersys, it may be a good idea to spend the day with Dr. Mays or Dr. Ting to get up to speed on their work. That way you will have a better understanding of Multistem. Then you can report back to us with real facts regarding the development progress of their late stage pipeline instead of blindly throwing them in with stem cell articles like your spaghetti article. I think your fellow scientists at Athersys would appreciate that and are certainly due that respect. Thank you.
Thanks Paul,
I appreciate you considering an interview with Athersys and I hope that you will bring it to fruition. Athersys is working with the FDA every step of the way and as you know Multistem is the only ARDS therapy with an FDA Fast Track designation.
While I respect your criticism of unproven stem cell clinics, the legitimate stem cell companies that are following the rules and working hard to bring life saving treatments to market through FDA regulated trials should be applauded. I look forward to your interview.
Thank you.
It seems you went out of your way to reverse engineer the reasoning for BARDA’s supposed funding decision on stem cell therapies as reported by the NY Times, 10 DAYS AGO,I might add. However, you failed to mention that more than one analyst has subsequently stated that the change at BARDA is not retroactive to ARDS stem cell submissions already in the BARDA pipeline based on direct contact with the companies involved:
My view is that if BARDA funding fails to materialize for Athersys, the politically motivated firing of hydroxychloroquine realist Rick Bright was the turning point as it signaled the clamping down on science based decision-making. When the top decision maker in the nation wants to run a clinical trial that injects a disinfectant into COVID-19 patients…. we have a problem.
Athersys met its endpoints in a Phase II clinical trial of ARDS and showed promising signals of efficacy for a small 30 patient trial. Look for yourself:
Not sure why you chose to disparage their work and promising data they have produced as “throwing spaghetti up against the wall”. I don’t believe you would appreciate being on the receiving end of dismissive criticism of your body of work when you are in the process of seeking grants and funding.
I actually singled out Athersys as the only one that had data and said if I were in their shoes I would have proceeded with COVID-19 work.
The spaghetti against the wall is meant for just the field throwing all kinds of cells against COVID-19 and hoping something sticks without having much foundation.
Paui, If you look at the overall article, especially “Rationales?” and “BARDA Concerns on Risks.. Immunity Target?” it comes off as entirely dismissive. Where in this article did you state “if I were in their shoes I would have proceeded with COVID-19 work.”. That was your prior article from 2 months ago! No one is going to go back and look at that article.
You have a big megaphone in the stem cell space and could use it for good. This comes off as a disparaging attempt to rationalize the motives of a U.S. Government Agency operating under a dysfunctional administration. As you surely know, the amount of effort, planning and money involved in running a successful 30 patient PHASE II clinical trial, in a tough indication like ARDS, is enormous You should appreciate this scientific approach given your justified criticisms of the stem cell clinics operating illegally in the country based on no evidence. You do no justice to your fellow scientists’ work at Athersys with this article that barely mentioned their work in just two meaningless sentences, in an otherwise dismissive article based on a dated NYT article. You can do better.
My feeling as an impartial person with no stake in any of these firms is that stem cells and other cell therapies in general are an extreme long-shot approach to COVID-19. Some may be more (Athersys) or less promising relatively speaking compared to each other, but even Athersys’ approach is probably a 1 in a 50 chance kind of thing in my view. Achieving safety and concrete efficacy is a huge task.
Please help me understand how, on one hand, you stated that you if you were in Athersys’ shoes you too would have proceeded with a COVID-19 study. As a scientist, I assume you made that statement based upon pre-clinical data, the amazing MultiStem study in a functioning pair of cadaver lungs where one lung served as a control, and the promising placebo controlled Phase II data that met its endpoints. Yet you still put the odds of success at 50-1? How does your assessment to move forward on COVID-19 ARDS make sense when you put the odds of success at 50-1?.
Stop it, everyone. The problem with MSCs is that they are not a defined cell type. Depending on where you get these connective tissue cells, how long and how you culture them, they are all different products. Other cell therapies, including hESC and iPSC-derived cells and CAR-T, require rigorous release criteria. Invest in science instead of marketing, and you’ll do far better. Right now you look too much like hype.
Paul ,
Have you thought about talking to BD for subsetting of T cells during Covid 19 , especially CD 4 activated cells related to MSC stem cells ,,,,CD 4 are lost in severe cases of Covid 19……Another thought ha e you interviewed the CEO Mesoblast? “Researchers and companies are also testing stem cell therapies, which are also believed to dampen the immune system. One company, Mesoblast, is testing its stem cell product in patients with severe Covid-19 as part of a clinical trial supported by an arm of the National Institutes of Health.” NY Time June 19, 2020..
In fact , Mesoblast’s Phase 3 #RandomizedControlledTrial of remestemcel-L in 300 ventilator-dependent patients with moderate to severe #COVID19 ARDS is underway in the US. Patient enrollment is expected to be completed within 3-4 months after the first patient was dosed in May.6, 2020……
Mesoblast’s RCT of remestemcel-L to treat #COVID19 Acute Respiratory Distress Syndrome (ARDS) is enrolling at hospitals across the US: CA, GA, IN, LA, MD, MA, MI, NH, NY, NC, OH, PA, TX, VA.
Complete list of hospitals participating:MSCs in COVID-19 ARDS
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT04371393
Recruitment Status : Recruiting
First Posted : May 1, 2020
Last Update Posted : June 19, 2020
See Contacts and Locations
Sponsor:
Icahn School of Medicine at Mount Sinai
Collaborator:
Mesoblast, Inc.
Information provided by (Responsible Party):
Annetine Gelijns, Icahn School of Medicine at Mount Sinai
Study DetailsTabular ViewNo Results PostedDisclaimerHow to Read a Study Record
Study Description
Go to sections
Brief Summary:
The mortality rate in SARS-CoV-2-related severe ARDS is high despite treatment with antivirals, glucocorticoids, immunoglobulins, and ventilation. Preclinical and clinical evidence indicate that MSCs migrate to the lung and respond to the pro-inflammatory lung environment by releasing anti-inflammatory factors reducing the proliferation of pro-inflammatory cytokines while modulating regulatory T cells and macrophages to promote resolution of inflammation. Therefore, MSCs may have the potential to increase survival in management of COVID-19 induced ARDS.
The primary objective of this phase 3 trial is to evaluate the efficacy and safety of the addition of the mesenchymal stromal cell (MSC) remestemcel-L plus standard of care compared to placebo plus standard of care in patients with acute respiratory distress syndrome (ARDS) due to SARS-CoV-2. The secondary objective is to assess the impact of MSCs on inflammatory biomarkers.
Condition or disease Intervention/treatment Phase
Mesenchymal Stromal Cells
Remestemcel-L
Acute Respiratory Distress Syndrome
COVID
Biological: Remestemcel-L
Drug: Placebo
Phase 3
Detailed Description:
This will be a randomized (1:1 ratio), double blind, parallel design, placebo controlled trial. Randomization will be stratified by clinical center and by moderate versus severe ARDS. The study is designed to have three interim analyses for stopping accrual early for efficacy and futility when 30%, 45% and 60% of the 300 patients have reached the primary endpoint using Bayesian predictive probabilities.
Patients will be randomized in a 1:1 allocation to intravenous infusion of MSCs (remestemcel-L) plus standard of care versus placebo plus standard of care for the treatment of COVID-19 related ARDS:
Group 1: 2×10^6 MSC/kg of body weight plus standard of care, administered twice during the first week, with the second infusion at 4 days following the first infusion (± 1 day)
Group 2: Placebo (Plasma-Lyte) plus standard of care, administered twice during the first week, with the second infusion at 4 days following the first infusion (± 1 day) (control)
MSCs and placebo will initially be administered intravenously in the dose defined above at randomization. The rate of infusion may be tailored to the patient’s respiratory status and fluid status, but the duration of infusion should not exceed 60 minutes.
Patients will be followed for 90 days post randomization, with assessment of pulmonary symptoms at 6 and 12 months.
Science must have the fortitude to withstand scrutiny. One can argue it must be scrutinized to be real science. We’ve seen retractions, and money grab, and many things that tarnish the reputation of science. Paul not always right in every post he does, but… the vast majority of concerns he raises are usually legitimate concerns. Sadly science and politics are forced to mingle more than most would like these days (ie the blockade on climate research by the current administration).
Do stem cells hold promise? Yes. Are there bad actors that need to be called out? Absolutely. Have far too many companies tried to jump on the ‘Treat/Cure COVID-19’ bandwagon… probably. Some might be for the right reason, but more than a few are looking for quick money (either profit or just grants/funding). It’s a hard call with the pandemic, how far do you push the ethical limits of quality risk-based medicine?
Paul’s done more research on some of these topics than many who comment. And he’s been willing to concede or update a post when credible information is brought to light. All in all it seems like he’s doing a A-level job with his blog. For this story, it seems more to the point of the politics involved than the science…
@Matt,
Thanks for the feedback and support.
If I’m wrong about stem cells or NK cells, etc. helping COVID-19 patients (and I hope I am) then I’ll be the first to post about it, point out my over-skepticism, and herald the success
In an off the cuff reaction to old news, the author takes is a broad swipe at a basket of unnamed stem cells companies, save one, without doing any actual research. I’d say the article reflects far more poorly upon the author then the stem cell companies discussed.
I had hoped to cover this story the day it broke, but life is busy.
Just curious — are you an investor in one or more of the stem cell/cell therapy companies with trials on COVID-19? Do you have one you think is most promising?
Paul,
With all due respect, If you are going to be writing about Athersys, it may be a good idea to spend the day with Dr. Mays or Dr. Ting to get up to speed on their work. That way you will have a better understanding of Multistem. Then you can report back to us with real facts regarding the development progress of their late stage pipeline instead of blindly throwing them in with stem cell articles like your spaghetti article. I think your fellow scientists at Athersys would appreciate that and are certainly due that respect. Thank you.
Perhaps it is time for another Athersys interview or even just chat off the record.
Thanks Paul,
I appreciate you considering an interview with Athersys and I hope that you will bring it to fruition. Athersys is working with the FDA every step of the way and as you know Multistem is the only ARDS therapy with an FDA Fast Track designation.
While I respect your criticism of unproven stem cell clinics, the legitimate stem cell companies that are following the rules and working hard to bring life saving treatments to market through FDA regulated trials should be applauded. I look forward to your interview.
Thank you.
@Paul,
It seems you went out of your way to reverse engineer the reasoning for BARDA’s supposed funding decision on stem cell therapies as reported by the NY Times, 10 DAYS AGO,I might add. However, you failed to mention that more than one analyst has subsequently stated that the change at BARDA is not retroactive to ARDS stem cell submissions already in the BARDA pipeline based on direct contact with the companies involved:
https://smbcnikko.bluematrix.com/sellside/EmailDocViewer?encrypt=dfb833a2-eab2-44f8-86d1-3e85a648e8b3&mime=pdf&co=smbcnikko&id=jdavis@radiusventures.com&source=mail
https://dawsonjames.com/wp-content/uploads/2020/06/ATHX.DJ_.6.22.2020.1.pdf
My view is that if BARDA funding fails to materialize for Athersys, the politically motivated firing of hydroxychloroquine realist Rick Bright was the turning point as it signaled the clamping down on science based decision-making. When the top decision maker in the nation wants to run a clinical trial that injects a disinfectant into COVID-19 patients…. we have a problem.
Athersys met its endpoints in a Phase II clinical trial of ARDS and showed promising signals of efficacy for a small 30 patient trial. Look for yourself:
https://www.athersys.com/clinical-trials/ards/default.aspx
Not sure why you chose to disparage their work and promising data they have produced as “throwing spaghetti up against the wall”. I don’t believe you would appreciate being on the receiving end of dismissive criticism of your body of work when you are in the process of seeking grants and funding.
I actually singled out Athersys as the only one that had data and said if I were in their shoes I would have proceeded with COVID-19 work.
The spaghetti against the wall is meant for just the field throwing all kinds of cells against COVID-19 and hoping something sticks without having much foundation.
Paui, If you look at the overall article, especially “Rationales?” and “BARDA Concerns on Risks.. Immunity Target?” it comes off as entirely dismissive. Where in this article did you state “if I were in their shoes I would have proceeded with COVID-19 work.”. That was your prior article from 2 months ago! No one is going to go back and look at that article.
You have a big megaphone in the stem cell space and could use it for good. This comes off as a disparaging attempt to rationalize the motives of a U.S. Government Agency operating under a dysfunctional administration. As you surely know, the amount of effort, planning and money involved in running a successful 30 patient PHASE II clinical trial, in a tough indication like ARDS, is enormous You should appreciate this scientific approach given your justified criticisms of the stem cell clinics operating illegally in the country based on no evidence. You do no justice to your fellow scientists’ work at Athersys with this article that barely mentioned their work in just two meaningless sentences, in an otherwise dismissive article based on a dated NYT article. You can do better.
My feeling as an impartial person with no stake in any of these firms is that stem cells and other cell therapies in general are an extreme long-shot approach to COVID-19. Some may be more (Athersys) or less promising relatively speaking compared to each other, but even Athersys’ approach is probably a 1 in a 50 chance kind of thing in my view. Achieving safety and concrete efficacy is a huge task.
Please help me understand how, on one hand, you stated that you if you were in Athersys’ shoes you too would have proceeded with a COVID-19 study. As a scientist, I assume you made that statement based upon pre-clinical data, the amazing MultiStem study in a functioning pair of cadaver lungs where one lung served as a control, and the promising placebo controlled Phase II data that met its endpoints. Yet you still put the odds of success at 50-1? How does your assessment to move forward on COVID-19 ARDS make sense when you put the odds of success at 50-1?.