MSCs enter COVID-19 treatment race with best source and optimal dosing key unanswered questions

Several companies developing mesenchymal stromal cells (MSCs) for COVID-19 saw significant stock movement after announcing their plans, and early data is indeed encouraging for further exploration in clinical trials, according to reporting from Manasi Vaidya, Pharma Writer for the Investigative News team at GlobalData, a leading data and analytics company. Yet, there are also several limitations with interpreting existing data, and the field is still grappling with questions on the ideal source for MSCs and optimal dosing strategies.

Vaidya explains: “MSCs have the inherent potential to spur tissue regeneration to possibly address the damage caused by acute respiratory distress syndrome (ARDS) commonly observed in COVID-19. This has seen cell therapy companies like Mesoblast and Pluristem reorient their focus to address the pandemic or players like Athersys accelerate its plans to evaluate its therapy in a large study.

“However, unlike biologics or antivirals being tested in COVID-19, the ability to scale-up manufacturing will be a critical component if MSCs are to be a panacea to all patients with COVID-related ARDS. While an ideal tissue source for the MSCs to be effective is not clear, each product may have to be weighed against supply constraints for the source material.”

Athersys’ product MultiStem is derived from multipotent adult progenitor cells, while Mesoblast’s remestemcel-L comprises culture-expanded mesenchymal stem cells. Pluristem Therapeutics’ PLX cells are described as mesenchymal-like stem cells. All three are allogeneic therapies. Early results with MSCs in ARDS due to COVID-19 have come from a China-based study and Pluristem’s compassionate use program.

Vaidya says: “The data provides further value in evaluating MSCs in larger clinical trials, but experts noted the results should be interpreted cautiously due to small patient numbers and the nonrandomized nature of the data. Additionally, several large, randomized ARDS and/or MSC trials have failed in the past despite early successes.” 

Mesoblast received its IND approval for remestemcel-L on 6th April, sending its stock up 65%. The company expects to initiate its study imminently, CEO Silviu Itescu told Vaidya. On 13th April, Athersys received an IND approval for MultiStem, and a study is planned to start this quarter. Also, on 13th April, Pluristem said it intends to file for the initiation of a multinational clinical trial using its PLX cells, which resulted in the stock peaking at 37% on that day.

Other MSC-focused companies in the fray include Orbsen Therapeutics, which initiated a Phase IIa trial in the UK last week with ORBCEL, which is made from umbilical cord tissue. Additionally, between 6th April and 13th April, Hope Biosciences won approval to start two Phase II trials evaluating its HB-adMSC product, manufactured from adipose tissue, and has a pending IND to evaluate its therapeutic potential. Hope CEO Donna Chang told Vaidya prior to its IND approval that the latter will be a randomized dose-escalation study, where participants will receive 50 million, 100 million or 200 million cells/dose or placebo.

Vaidya adds: “The optimal dosing is a key question that trials will be looking to determine. Additionally, a strategy that allows multiple dosing may be beneficial but could be logistically difficult given the critical nature of these ARDS patients. Furthermore, while companies are largely evaluating these therapies in patients with moderate-to-severe ARDS, the ideal timing for initiating treatment given the varying levels of lung damage still needs to be understood.”

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