While 55% of Americans have never heard of sepsis, it is the third leading cause of mortality in the United States following heart disease and cancer.
Sepsis is a highly heterogeneous syndrome that is caused by an unbalanced immune host response to an infection. The first use of the term ‘sepsis’ in a medical context was probably in poems by Homer that date from more than 2,700 years ago, but sepsis was not clinically defined until the early 1990s when a group of key opinion leaders released the first consensus definition of sepsis.
Herein, sepsis was defined as a systemic inflammatory response syndrome (SIRS) caused by an infection; increasing severities were designated ‘severe sepsis’ (referring to sepsis and organ dysfunction) and ‘septic shock’ (referring to sepsis and refractory hypotension).
In the most recent ‘Sepsis‑3’ consensus definition, sepsis is defined as a life-threatening organ dysfunction that is caused by a dysregulated host response to infection, and the term severe sepsis has been removed.
Of note, although infection is the triggering event in this definition of sepsis, the aberrant immune response often remains after successful treatment of the infection. Sepsis clearly imposes a substantial global burden in terms of morbidity and mortality. Nearly all patients with severe sepsis require treatment in an intensive care unit (ICU).
Sepsis, which has been identified by the World Health Organization (WHO) as a global health priority, has no proven pharmacologic treatment other than appropriate antibiotic agents, fluids, and vasopressors as needed. Reported death rates among hospitalized patients range between 30% and 45%, and one out of three patients who died in a U.S. hospital had Sepsis.
Allocetra™ is being developed as an adjunctive therapy for preventing organ failure and mortality in sepsis, in combination with existing antibiotics agents. It is designed to offer a true paradigm shift in the quest to solve a complex healthcare challenge.
On March 18, 2020, the Company announced the final safety and efficacy data from the Company’s completed Phase Ib. The final analysis compared the clinical data of 10 patients admitted to the intensive care unit with sepsis who were administered Allocetra™ upon their admission, with 37 patients who were matched controls (matched by age, gender, Sequential Organ Failure Assessment (SOFA) score, and infection source) who received only the standard of care treatment at the same hospital during 2014-2019 but did not receive Allocetra™. The clinical trial was conducted at Hadassah Medical Center, which is one of the largest and most prestigious hospitals in Israel (“Haddasah”). The Acute Physiology and Chronic Health Evaluation (APACHEII) score of the Allocetra™-treated group was 12.3, and the corresponding probability of mortality of at least one patient in that group was predicted at 85% based on the hospital’s ICU staff’s clinical assessment of each patient’s overall condition at admission. However, none (0%) of the Allocetra™-treated patients died during the 28-day study period, as compared to 27% 28-day mortality in the matched controls group. Each of the 10 Allocetra™-treated patients had between 2 to 5 dysfunctional organ systems upon admission to the ICU. All (100%) of the Allocetra™-treated patients had rapid and complete recovery from their septic conditions and of any organ dysfunction that was present upon admission to the ICU. Despite the similarity of organ-failure state (SOFA) at entry between the Allocetra™-treated patients and the matched controls group (average of 3.4 versus 3.47), not a single patient treated with Allocetra™ had any increase in organ-failure state post administration of Allocetra™, while the majority of the patients in the matched controls group had an increase in organ-failure state. The average worsening in organ-failure state of patients in the matched controls group was approximately 100% compared with their ICU hospitalization state vs zero (0%) percent worsening in organ-failure state of Allocetra™-treated patients post administration of Allocetra™ (p< <0.0001). The ICU length-of-stay for all Allocetra™-treated patients was significantly shorter than those patients who received only the standard of care, with an average of 4 days compared to 11.11 in the matched controls group, a 64% reduction (p<0.0001). The slowest ICU discharge of a patient treated with Allocetra™ was after 8 days, while approximately 50% of the matched controls group were still at the ICU after 28 days. Allocetra™ was shown to be safe and tolerable, with no serious unexpected severe adverse reactions and no serious adverse events.
Summary of Planned Clinical Trials of Allocetra™ for the treatment of Organ Dysfunction and Failure Associated with Sepsis
In light of the encouraging results of the Phase Ib in patients with severe sepsis, the Company plans, subject to regulatory approvals, to initiate a Phase IIb or Phase II/III clinical trial with Allocetra™ for the treatment of organ dysfunction and failure associated with sepsis during 2020. The Company currently intends to enroll up to 100 patients in such a clinical trial. The Company intends, subject to the clinical trial results, to request a conditional marketing authorization from the EMA for this indication.