Direct Biologics Announces Publication of Significant Survival Benefit with ExoFlo™ in its Phase 2 Randomized Controlled Clinical Trial in the Journal CHEST

Direct Biologics, LLC, a late-stage biotechnology company leveraging its regenerative medicine platform using extracellular vesicles (EVs) secreted from bone marrow-derived mesenchymal stem cells (BM-MSCs) to address multiple disease indications, announces favorable safety data and significant efficacy results from its Phase 2 clinical trial (NCT04493242) of ExoFlo™ in hospitalized adult COVID-19 patients with moderate-to-severe acute respiratory distress syndrome (ARDS).

These results were published in the June 2023 edition of the peer-reviewed medical journal CHEST in a paper titled “Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicle Infusion for the Treatment of Respiratory Failure from COVID-19: A Randomized Placebo Controlled Dosing Clinical Trial” by lead author Amy L. Lightner, M.D., Chief Medical Officer of Direct Biologics.

“This prospective, double-blind, randomized, placebo-controlled Phase 2 trial is the first clinical study to show BM-MSC EVs are safe and exhibit potential for efficacy based on post-hoc subgroup analyses in the treatment of respiratory failure or ARDS related to COVID-19,” said Joe Schmidt, President and co-founder of Direct Biologics. “A critical finding of this study was the safety profile of ExoFlo. There was a lack of adverse or serious adverse events in this very sick patient population. This overwhelming safety profile is highly encouraging for our future development pathway in patients with ARDS.”

This prospective Phase 2 multicenter, double-blind, randomized, placebo-controlled trial was conducted at five sites across the U.S. with infusions of placebo, 10 mL of ExoFlo or 15 mL of ExoFlo on Day 1 and Day 4. A total of 102 patients with COVID-19 associated moderate-to-severe ARDS were enrolled and randomized. Adverse events were documented throughout the trial period. The primary outcome measure was all-cause 60-day mortality rate. Secondary outcomes included time to death (overall mortality), the incidence of treatment-emergent serious adverse events, proportion of discharged patients at Day 7, Day 30 and Day 60, time to hospital discharge and ventilator-free days (VFDs).

Over the duration of the clinical trial, no treatment-related adverse events were reported. The overall mortality rate among all subjects was 61.0%. For the post-hoc subgroup analyses, those with respiratory failure had a 60-day mortality of 50.0% in the placebo group and 19.2% in the ExoFlo-15 group, representing an absolute risk reduction of 30.8% and a relative risk of 0.385 (95%CI=0.159,0.931, p=0.0340).

For those aged 18-65 years who met modified Berlin criteria for moderate-to-severe ARDS, the 60-day mortality was 72.7% in the placebo group and 30.8% in the ExoFlo-15 group, yielding an absolute risk reduction of 41.9% and a relative risk of 0.423 (95%CI=0.173,1.032, p=0.0588). For the 18-65 year age group, the number of VFDs in the ExoFlo-15 group was improved compared with placebo (47.6 days versus 30.3 days, respectively). In addition, a trend in dose response was observed for VFDs in both moderate and severe ARDS in this age group.

Based on preliminary results previously demonstrated from ExoFlo, the FDA issued a regenerative medicine advanced therapeutic (RMAT) designation and also authorized proceeding with a double-blind, placebo-controlled Phase 3 clinical trial of ExoFlo for the treatment of all-cause ARDS.

“Given the limited number of approved therapeutics with a proven mortality benefit, expedient results of our ongoing Phase 3 trial will be critical to the treatment of ARDS patients,” said Mark Adams, Chief Executive Officer and co-founder of Direct Biologics. “It is truly exciting to see a novel regenerative medicine platform technology with this safety record and potential to treat a patient population comprising 15% of all ICU patients, as well as any future pandemic where ARDS is a leading cause of mortality.”


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