Investors were disappointed in data from a mid-stage study of Enlivex Therapeutics’ Allocetra cell therapy for the treatment of sepsis. The Israeli company is considering a follow-on trial in sepsis caused by urinary tract infection.
Reported trial bias issues sent Enlivex Therapeutics’ stock plummeting 50% after the company shared mixed results for its Phase II study of cell therapy Allocetra for the treatment of sepsis.
The trial enrolled patients with sepsis caused by pneumonia, internal abdomen and urinary tract infections to test Enlivex’s cell therapy alongside standard of care. A stand-alone analysis showed Allocetra reduced overall mortality rate by 65% compared to expected mortality.
However, patient randomization “biases” were the sticking point for Enlivex. The randomization resulted in the Allocetra cohort showing a 20% higher frequency of septic shock and 35% higher frequency of invasive ventilation before treatment.
“Both of these patient attributes are associated with significantly higher degree of difficulty of treatment and higher mortality rates, and potentially resulted in patients with more severe sepsis in the Allocetra-treated cohorts,” Enlivex CEO Oren Hershkovitz said in a statement. “These biases made it challenging to deduce the relative effect in other patient subgroups.”
The treatment appeared most effective in the urinary tract infection (UTI) cohort, resulting in a 90% reduction in the primary endpoint of the sequential organ failure assessment (SOFA) score at 28 days. Pneumonia-source sepsis patients showed a 68% SOFA reduction while those whose infection source was internal abdomen resulted in a 36% reduction.
The Israel-based biotech is currently considering a potential follow-on study focused only on high-risk UTI patients. According to Enlivex, up to a third of sepsis cases start as UTIs and lead to as many as 1.6 million deaths across the U.S. and Europe.
Allocetra is the company’s off-the-shelf cell therapy designed to reprogram macrophages, white blood cells considered the body’s primary cleanup system, into their homeostatic state. Solid cancers, sepsis and other diseases cause the cells to reprogram out of that state, contributing to the severity of disease.
In September 2023, Enlivex announced it would cease development of Allocetra in oncology indications, citing new guidelines from the FDA with the potential to result in longer clinical development. The company shifted its focus to inflammatory and autoimmune indications, while laying off 50% of its staff to extend Enlivex’s cash runway through the end of 2025.
Kate Goodwin is a freelance life science writer based in Des Moines, Iowa. She can be reached at kate.goodwin@biospace.com and on LinkedIn.
