Biopharma companies that are focused on cell therapies have reported promising clinical trial results in their ability to treat acute respiratory distress syndrome (ARDS), a condition that has shown to be a significant contributor to higher mortality in COVID-19 cases. In an Alliance for Regenerative Medicine (ARM) webinar on the topic, Michael Lehmicke, director, science and industry affairs at ARM, noted that developers are utilizing mesenchymal stem cells (MSCs) and other stromal cells to treat ARDS caused by COVID-19. The number of clinical trials now underway continues to increase with many more at the preclinical stage.
Webinar participant Eric Jenkins, senior medical director and head of clinical operations at Cleveland-based Athersys Inc., described the company’s work using its Multistem candidate, which is available frozen, off-the-shelf and derived from the bone marrow of adult donors. The company initiated the large, pivotal MACOVIA phase II/III study that will enroll up to 400 COVID-19 patients to treat those with moderate to severe ARDS.
In earlier work last year, results from an exploratory phase II trial completed by the company and participating pulmonary critical care centers in the U.K. and the U.S. showed that when patients with ARDS were treated with a single infusion of intravenous Multistem within the first few days of being ventilated, there was a substantial reduction in mortality, improvement in pulmonary function, increased ventilator-free days and ICU-free days during the 28-day clinical assessment period, and meaningfully better outcomes in quality of life and recovery over one year, added Gil Van Bokkelen, chairman and CEO of Athersys.
The first cohort of the latest study is a single active treatment arm to evaluate the safety of two dose levels of Multistem. If it is well-tolerated, the study is designed to further evaluate the efficacy, safety and tolerability in that patient population. The primary efficacy endpoint for the study will compare the number of ventilator-free days through day 28 among Multistem and placebo treatment groups.
Taming the immune response
Racheli Ofir, vice president of research and intellectual property at Haifa, Israel-based Pluristem Therapeutics Inc., described during the webinar the company’s PLX cells that are available off-the-shelf and, once commercialized, can be manufactured in large-scale quantities. They are allogeneic mesenchymal-like cells that have immunomodulatory properties that induce the immune system’s natural regulatory T cells and M2 macrophages and may prevent or reverse the dangerous overactivation of the immune system.
The company has started enrollment in its U.S. phase II study of PLX cells for the treatment of severe COVID-19 complicated by ARDS. The 140-patient study is evaluating the efficacy and safety of intramuscular injections of PLX-PAD with the primary endpoint being the number of ventilator-free days during the main 28-day study period. Safety and survival follow-up will be conducted at weeks eight, 26 and 52.
In May, Melbourne, Australia-based Mesoblast Ltd. said it dosed the first patients in a 300-patient U.S. phase II/III trial of its allogeneic cellular medicine, remestemcel-L, in COVID-19-infected patients with moderate to severe ARDS on ventilator support. The trial will randomize up to 300 ventilator-dependent patients in intensive care units to either remestemcel-L or placebo (1-to-1) on top of maximal care. The primary endpoint is all-cause mortality within 30 days of randomization, with the key secondary endpoint being the number of days alive and off mechanical support.
The study followed initial promising results from use of remestemcel-L in patients with moderate to severe COVID-19 ARDS under an emergency IND application or expanded access protocol at the Mount Sinai Hospital in New York.
Houston-based Hope Biosciences Inc.’s adipose-derived mesenchymal stem cells (HB-adMSCs) are being studied in a phase II trial that is expected to enroll 110 hospitalized patients into two separate arms. Participants taking hydroxychloroquine and azithromycin will be randomized into a placebo or treatment group and patients not on that regimen will also be randomized into a placebo or treatment group. Those receiving treatment will receive four doses of 100 million HB-adMSCs over a 10-day period. Results of the study are expected in April next year.
In the pipeline
Some of the other therapies that have entered clinical trials include Lattice Biologics Ltd., of Belgrade, Mont., which reported it plans to evaluate its amniotic fluid concentrate, Amnioboost, in patients with ARDS. The company said it believes the fluid to have immunomodulatory properties to counteract the inflammatory processes implicated in several diseases by down-regulating production of pro-inflammatory cytokines, increasing production of anti-inflammatory cytokines and enabling recruitment of naturally occurring anti-inflammatory cells to involved tissues.
To help fund the study, the company entered an agreement with Alumina Partners (Ontario) Ltd. for a commitment of up to CA$6 million (US$4.49 million) in an at-will offering facility. Over a two-year period, the company has the right to draw down on the facility, at any time, at its sole election, in equity private placement tranches of up to CA$1 million.
Celltex Therapeutics Inc., of Houston, received FDA approval to proceed with its IND trial, a phase II study that will evaluate the safety and prophylactic efficacy of autologous adipose tissue-derived mesenchymal stem cells (AdMSCs) against COVID-19. Celltex will enroll 200 patients in the study who have never been infected by COVID-19, half of which will receive intravenous infusions of AdMSCs while the other 100 will receive placebo treatments. The primary objective is to evaluate overall safety of AdMSCs, and the secondary objective is to demonstrate the efficacy of AdMSCs as a prophylactic medicine for those at a high risk of contracting the virus.
In April, Salt Lake City-based Predictive Biotech, a wholly owned subsidiary of Predictive Technology Group, submitted an emergency use authorization application with the FDA for the immediate use of mesenchymal stem cells derived from umbilical cord tissue (UC-MSCs) for the treatment of ARDS. The proposed IND clinical trial will utilize Predictive’s Corecyte product, derived from umbilical cord tissue to assess the efficacy as an add-on therapy to standard treatment of patients with severe ARDS, secondary to COVID-19.