Danish Regulators Authorize Allocetra Trial

The Danish Medicines Agency (DKMA) authorized Enlivex Therapeutics Ltd.’s multi-country, randomized, controlled Phase I/II trial evaluating Allocetra as a knee osteoarthritis (KO) treatment. The company received the trial’s first regulatory approval in January from the Israeli Ministry of Health.
 
The Phase I/II multi-center trial is composed of two stages. The first stage is a safety run-in, open-label dose escalation phase to characterize the safety and tolerability of Allocetra injections to the target knee in order to identify the dose and injection regimen for the second, randomized stage, which will involve 160 patients with moderate to severe KO. The second stage is a double-blind, randomized, placebo-controlled stage that will begin after the safety run-in stage and confirmation by the independent Data and Safety Monitoring Board. In addition to evaluating safety, the blinded randomized stage is statistically-powered to assess the efficacy of Allocetra knee injections. The company expects the primary measurements will evaluate joint pain and joint function compared to a placebo at three months, six months, and 12 months after treatment.  
 
“We are excited to push ahead with the clinical development of Allocetra in osteoarthritis,” Enlivex CEO Oren Hershkovitz, Ph.D., said. “The approval of the study in Denmark, which is expected to be the leading recruiting country in the trial, marks an important step, as this is the first approval for this trial by a European agency. The Danish sites are experienced in conducting osteoarthritis studies with high recruitment rates and high quality.”

Allocetra is being developed as a universal, off-the-shelf cell therapy designed to reprogram macrophages into their homeostatic state. Diseases such as solid cancers, sepsis, and many others reprogram macrophages out of their homeostatic state. These non-homeostatic macrophages contribute significantly to disease severity. By restoring macrophage homeostasis, Allocetra can potentially provide an immunotherapeutic mechanism of action for life-threatening clinical indications, as a stand-alone therapy, or in combination with therapeutic agents.
 
Osteoarthritis is the most common form of arthritis, affecting more than 32.5 million Americans and more than 300 million individuals worldwide.¹ About half of knees with ACL injuries develop osteoarthritis within five to 15 years. Seventy-eight million Americans are projected to be afflicted with osteoarthritis by 2040. Symptomatic KO is particularly prevalent and disabling, with 40% of men and 47% of women developing the condition in their lifetimes. Osteoarthritis accounts for more than 1 million hospitalizations annually in the United States, primarily for total joint replacement. There are currently no medications approved by either the U.S. Food and Drug Administration or the European Medicines Agency that have been demonstrated to arrest, slow, or reverse progression of structural damage in the joint.
 
Enlivex is a clinical stage macrophage reprogramming immunotherapy company in Israel developing Allocetra, a universal, off-the-shelf cell therapy designed to reprogram macrophages into their homeostatic state. Resetting non-homeostatic macrophages into their homeostatic state is critical for immune system rebalancing and resolution of life-threatening and life-debilitating conditions. 

Reference
¹ Source: The Arthritis Foundation; Disease modification in osteoarthritis; pathways to drug approval, Katz et. Al., Osteoarthritis and Cartilage Open (2) (2020).