Stem cells, ARDS, and COVID-19
I’ve already written two pieces about the idea of using stem cells to battle COVID-19 (here and here), the sometimes fatal disease that arises from infection with the novel coronavirus. Older patients and those with underlying conditions are those at greatest risk of severe disease that results in hospitalization, entry into the ICU, and in some cases death.
One of the key elements of COVID-19 leading to bad outcomes is acute respiratory distress syndrome (ARDS). Both Athersys (Cleveland, OH) and Mesoblast (Melbourne, AU) have stem cell products that might help ARDS. Although it’s too soon to be sure if these products definitely help ARDS and might be helpful for COVID-19, there is some enthusiasm for testing this out.
The general idea is that the stem cells would reduce the damaging hyperactivity of the immune system in these patients. Unfortunately, that means that the stem cell products could not be tested for this function in vitro on cell cultures. You can see an image of a culture of cells at right from the Pasteur Institute that were cultured with the novel coronavirus, which killed the cells on the right part of the image.
Athersys’ core product is called MultiStem, which is an allogeneic marrow-derived cellular drug thought to reduce inflammation. In a 2019 report on data including from Phase 2a, the company reported encouraging results on safety. A one-year follow-up report released this January was also encouraging, with these key bullet points:
- “Previously observed lower mortality for MultiStem-treated subjects compared to placebo (particularly among the prospectively defined subset of more severe ARDS patients) persisted out to one-year of follow-up;
- Day-365 Quality of Life (QoL) outcomes, assessed by the EQ-5D, were meaningfully better among all survivors who received MultiStem treatment compared to those who received placebo;
- Within the prospectively defined group of patients with more severe ARDS, MultiStem treatment was associated with a markedly greater rate of survival and progression to functional independence at one year (i.e., self-care);
- As measured at day-28, MultiStem treatment was associated with a higher mean ventilator-free day (VFD) score of 12.9 vs. 9.2 in the placebo group, and a higher mean intensive care unit (ICU)-free day score of 10.3 vs. 8.1 in the placebo group;
- As measured at day-28, among more severe ARDS patients, mean VFD in the MultiStem subgroup was 14.6 vs. 8.0 in placebo subgroup. Mean ICU-free days were 11.4 vs. 5.9 for MultiStem and placebo recipients, respectively;
- Lower inflammatory cytokine levels at day-7 in the MultiStem group relative to the placebo group, including IFNg, IL-6 and IL-1b among others, suggest the potential for MultiStem treatment to abate the severe inflammatory response associated with ARDS; and
- MultiStem treatment was well tolerated in this very sick ARDS patient population, with no serious adverse events related to administration through one year of follow-up.”
There are some hints toward efficacy although the study was not powered for determinations of efficacy. Athersys stock is up substantially in the past week.
Mesoblast announced in a PR today entitled, “MESOBLAST TO EVALUATE ANTI-INFLAMMATORY CELL THERAPY REMESTEMCEL-L FOR TREATMENT OF COVID-19 LUNG DISEASE” that it is exploring the use of its MSC product Remestemcel-L for the novel coronavirus.
Remestemcel-L is more well-known as a cellular drug for graft versus host disease (GVHD) but may have broader applicability as an immune-modulatory agent. The stock is up almost 20% at this moment.
From the PR:
“Remestemcel-L has potential for use in the treatment of ARDS, which is the principal cause of death in COVID-19 infection. This is supported by recently published results from an investigator-initiated clinical study conducted in China which reported that allogeneic MSCs cured or significantly improved functional outcomes in all seven treated patients with severe COVID-19 pneumonia.
Additionally, in post-hoc analyses of a 60-patient randomized controlled study in chronic obstructive pulmonary disease (COPD), remestemcel-L infusions were well tolerated, significantly reduced inflammatory biomarkers, and significantly improved pulmonary function in those patients with elevated inflammatory biomarkers. Since the same inflammatory biomarkers are also elevated in COVID-19, these data suggest that remestemcel-L could be useful in the treatment of patients with ARDS due to COVID-19. The COPD study results have been submitted for presentation at an international conference, with full results to be submitted for publication shortly.”
Notably, Mesoblast cited the small Chinese coronavirus study results that I’ve blogged about before, which I felt were hyped by researchers/journalists. Just because these studies were hyped doesn’t mean there’s “no there there” but we just need to be cautious.
Looking ahead on stem cells for coronavirus
One thing I’m still sorting through more broadly is the question of the possible mechanisms by which IV stem cells like those from the two biotechs could help COVID-19. Some stem cells that are given IV do end up in the lungs, but once there, how are they doing? Mostly dead within a day or two, or a decent number surviving and able to do something useful? Or could stem cells given IV help ARDS and maybe COVID indirectly via a broader immune modulating function?
I have to admit not having followed Athersys or Mesoblast as closely the last couple years so perhaps they have already talked more about immune mechanisms of these products. I’m also betting we’ll have some fans of those biotechs weigh in with helpful comments.
Disclosure, I listed and discussed the companies alphabetically and have no financial interest in them or any competitors.