Ann: DSMB Analysis Recommends to Continue P3 COVID-19 ARDS Trial, page-5

SECOND INTERIM ANALYSIS OF CLINICAL OUTCOMES AFTER 135 PATIENTS RESULTS IN RECOMMENDATION TO CONTINUE REMESTEMCEL-L PHASE 3 TRIAL IN COVID-19 ARDS
Melbourne, Australia; November 11, and New York, USA; November 10, 2020: Mesoblast Limited (ASX: MSB; Nasdaq: MESO) today announced that the randomized controlled Phase 3 trial of remestemcel-L in patients with moderate to severe acute respiratory distress syndrome (ARDS) due to COVID-19 infection had received a recommendation to continue from the independent Data Safety Monitoring Board (DSMB) following completion of the trial’s second interim analysis. The analysis was performed on the trial’s first 135 patients, 45% of the total target of up to 300 randomized patients, with the DSMB recommending continuation after reviewing the trial’s primary endpoint, all-cause mortality within 30 days of randomization and all safety data. The key secondary endpoint is days alive off mechanical ventilatory support within 60 days of randomization.
Mesoblast Chief Medical Officer Dr Fred Grossman said: “We are very pleased with the recommendation by the DSMB, as we seek to confirm whether remestemcel-L improves survival in ventilated COVID-19 patients with moderate to severe ARDS. Patients who have co-morbidities or are older are likely to continue to be at high risk of ARDS and death,1-3 even if COVID-19 vaccines become available. This is why having a potential treatment that reduces mortality in these patients is so important.”
ARDS is the principal cause of death in COVID-19 infection and is thought to be due to a dysregulated immune response in the lungs to COVID-19. Deaths continue to increase in ventilator-dependent ARDS patients as COVID-19 cases continue to surge globally. Despite improved treatment and earlier intervention in hospitalized COVID-19 patients overall, the mortality rate in COVID-19 ARDS patients who are over 60 years old remains more than 60%.1 These patients appear to be particularly refractory to corticosteroids such as dexamethasone 4-5 and have not responded to single cytokine antagonists, anti-virals, or anti-malaria agents.
The Phase 3 trial aims to confirm findings from a pilot study at New York’s Mt Sinai Hospital in March- April this year where nine of 12 ventilator-dependent patients (75%) were successfully discharged from hospital a median of 10 days after receiving two intravenous doses of remestemcel-L within five days. The ongoing Phase 3 trial, which is treating patients across more than 20 hospitals in the United States, uses the same dosing regimen.
Mesoblast holds an Investigational New Drug (IND) submission for remestemcel-L in COVID-19 ARDS, with trial size, protocol design, and endpoints developed with input from the United States Food and Drug Administration. The third and final interim analysis, when 60% of the randomized target has completed 30 days of follow-up, will occur in the coming weeks.
References
1.Mortality of COVID-19 Admitted Patients on Mechanical Ventilators. Epic Health Research Network. June 26, 2020
2. Harrison SL., et al. Comorbidities associated with mortality in 31,461 adults with COVID-19 in the United States: A federated electronic medical record analysis. PLOS Medicine. September 10, 2020. https://doi.org/10.1371/journal.pmed.1003321
3. Sanyaolu A., et al. Comorbidity and its Impact on Patients with COVID-19. SN Compr Clin Med. 2020 Jun 25: 1-8. doi: 10.1007/s42399-020-00363-4
4. Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report. New England Journel of Medicine. July 17, 2020. DOI: 10.1056/NEJMoa2021436
5. Tomazini BM., et.al. Effect of Dexamethasone on Days Alive and Ventilator-Free in Patients With Moderate or Severe Acute Respiratory Distress Syndrome and COVID-19. JAMA 2020;324(13):1307- 1316.