Acute Respiratory Distress Syndrome (ARDS)

COVID-19 and other Viral Induced ARDS

Recent clinical and epidemiological data confirms that the primary cause of serious or critical illness, and the most frequent cause of death following COVID-19 infection is acute respiratory distress syndrome (ARDS), which can be induced by the virus. While many individuals will recover from viral infection after experiencing only mild to modest symptoms, a range of viral pathogens can induce severe pulmonary inflammation in patients, including SARS, MERS, virulent influenza (e.g., H1N1), and COVID-19. When the lungs become inflamed they accumulate fluid, a process referred to clinically as edema, and the lung tissue becomes structurally abnormal. This results in lung function becoming significantly compromised, preventing normal oxygenation, and resulting in serious or critical illness as well as death in some patients.  

Unfortunately, there is no FDA approved and effective medicine for ARDS.  The current standard of care is to place patients on a ventilator, which forces oxygen into the lungs to keep the patient alive.  Unfortunately, given the current limitations in standard of care, the morbidity and mortality from ARDS is high, especially among older patients and patients with underlying health issues or co-morbid conditions.  Patients with ARDS that are ventilated for an extended period of time and survive frequently experience long term pulmonary damage due to ventilator induced fibrosis and scarring, and also experience compromised quality of life.

Currently MultiStem is the only investigational therapy that has shown promise for the treatment of ARDS that has been granted Fast Track designation by the FDA.

In May 2019 we presented positive results from a randomized, double blind, placebo controlled exploratory clinical study evaluating MultiStem cell therapy for treatment of ARDS at the American Thoracic Society Meeting in Dallas. ARDS is a serious immunological and inflammatory condition characterized by widespread inflammation in the lungs. ARDS can be triggered by pneumonia, sepsis, or trauma and represents a major cause of morbidity and mortality in the critical care setting. It has significant implications, as it prolongs intensive care unit (ICU) and hospital stays and requires convalescence in the hospital and rehabilitation.

Patients in the exploratory study were evaluated through 28 days for the primary clinical assessment and were further assessed through a one-year follow-up period. We announced the encouraging one year data in January of 2020. Data highlights from the trial include the following:

  • Lower mortality of 25% in the MultiStem treatment group vs. 40% in the placebo group;
  • 40.2% higher ventilator-free (VF) days, (12.9 VF days in the MultiStem treatment group vs. 9.2 VF days for the placebo group);
  • 27.2% higher ICU-free days, (10.3 days in MultiStem subjects vs. 8.1 days for subjects receiving placebo);
  • Rapid improvement in pulmonary function was observed among MultiStem treated subjects, with 45% of these patients achieving ventilator independence by study day 7 vs only 20%  placebo in the placebo group; 
  • In more severe ARDS patients (as evident from a prospectively defined analysis), the difference between MultiStem treatment and placebo was greater – 25% mortality in MultiStem group vs. 50% in placebo group, 14.6 VF days in MultiStem group vs. 8.0 VF days in placebo group, and 11.4 ICU-free days in MultiStem group versus 5.9 ICU-free days in placebo group; 
  • 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); and
  • MultiStem treatment was well tolerated in this very sick ARDS patient population, with no serious adverse events related to administration.

The study was designed to evaluate the impact of MultiStem treatment in subjects with acute onset of moderate to severe ARDS and was conducted at sites in the United States and United Kingdom. The study included two parts – a small initial dose confirmation phase, followed by the larger double blinded, placebo-controlled and randomized phase (Phase 2a portion). Treatment was required to begin within four days of ARDS diagnosis with an average treatment time of approximately two days from the diagnosis. Six subjects were treated with MultiStem in the initial portion of the study, and in the Phase 2a portion of the study, 20 subjects were treated with an intravenous (IV) administration of 900 million MultiStem cells and 10 subjects received IV placebo. As disclosed previously, the study was not powered for the efficacy outcomes. Based on the study results, the Company is planning further development in this area and intends to submit for publication the detailed study data.

In May 2019 we announced that our planned Phase 3 study for ARDS has received Fast Track Designation from the FDA.  In addition, our partner HEALIOS K.K. is currently running the ONE-BRIDGE study using MultiStem cell therapy. On November 14, 2019, HEALIOS K.K. received notification of Orphan Designation for their ARDS program, which is meant to expedite the regulatory process for development and provides other meaningful benefits.

There are limited interventions and no effective drug treatments for ARDS, making it an area of high unmet clinical need with high treatment costs. Given ARDS high treatment costs, a successful cell therapy could be expected to generate significant savings for the healthcare system by reducing days on a ventilator, days in the ICU and total days in the hospital, and importantly, could reduce mortality and improve quality of life for those suffering from the condition. The medical need for a safe and effective treatment of ARDS is significant due to its high mortality rate, and it annually affects approximately 400,000 - 500,000 patients in Europe, the United States and Japan, alone.

After undergoing multiple reviews. BARDA has designated MultiStem® as a “Highly Relevant” therapeutic for COVID-19. We now are working to expedite the further advancement of the program. Our near-term priorities are to finalize and implement an alliance with BARDA, and to work with FDA, BARDA and other regulators to design and initiate COVID-19 induced ARDS study as soon as possible.