Study: Cell Therapy Helps Knee Osteoarthritis Patients Avoid Surgery

Immunotherapy firm Enlivex Therapeutics Ltd.’s cell therapy appears to be a viable alternative treatment option for knee osteoarthritis.

Interim study data from a phase I/II investigator-initiated clinical trial of Allocetra show the injectable product can help reduce the pain associated with the degenerative condition and enable patients to avoid knee replacement surgery. The study enrolled nine patients with end-stage knee osteoarthritis who had been indicated for knee replacement surgery. 

“After a robust experience with systemic infusions of Allocetra across multiple clinical studies, this is the first report of clinical outcomes following a focused Allocetra injection to the joint,” Enlivex Vice President of Medical Einat Galamidi, M.D., stated. “We believe the results confirm the safety of Allocetra in the local setting and pave the way to further explore the potential therapeutic utilization of Allocetra in joint diseases with inflammatory involvement.”  

Study subjects were given a single Allocetra injection to the knee as a potential “last resort” alternative for pain resolution and knee functionality in lieu of knee replacement surgery, and evaluated for at least three months after treatment. Patients reported pain using a scale of zero (0, representing no pain) to 10 (representing maximum pain). 
 
The three-month follow up showed a 64% average reported pain reduction compared to baseline, with 89% (eight of nine) of treated patients reporting an improvement in their knee pain compared to their baseline pain before treatment, and 33% (three of nine) of the patients reporting complete pain relief—from an average pain level of nine to a pain level of 0. In all cases, dosing was successfully completed, and there were no severe related adverse events after treatment.
 
During the three-month post-injection period, only one patient (11%) decided to undergo knee-replacement surgery, while 89% (eight of nine patients) decided not to proceed with the procedure. 
 
The investigator-initiated trial is led by Amir Oron, M.D., a senior orthopedics specialist and chief of hand surgery and microsurgery at the Kaplan Medical Center in Rehovot, Israel. “I am pleased with the interim results of this trial, demonstrating the safety of an Allocetra injection to the knee in nine patients with severe end-stage knee osteoarthritis,” Oron said. “The initial signal of response to the Allocetra injection is encouraging, especially as these patients have attempted multiple other treatments with no lasting improvement. These patients have severe osteoarthritis of the knee and need better treatment options to replace or delay progression to extensive surgery.”

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 the severity of the respective diseases. By restoring macrophage homeostasis, Allocetra can potentially provide an immunotherapeutic mechanism of action for life-threatening clinical indications that are defined as “unmet medical needs,” as a stand-alone therapy or in combination with leading therapeutic agents.
 
Recruitment to the study and long-term follow up are ongoing. The study aims to enroll a total of 18 patients to be treated with a single injection of Allocetra to the afflicted knee. Patients are assessed for safety following dosing, and pain and function responses to treatment up to 12 months after the injection.
 
Osteoarthritis is the most common form of arthritis, affecting more than 32.5 million Americans and over 300 million individuals worldwide. About half of knees with ACL injuries develop osteoarthritis within five to 15 years. Roughly 78 million Americans are projected to have osteoarthritis by the year 2040, according to industry statistics. Symptomatic knee osteoarthritis is particularly prevalent and disabling, with 40% of men and 47% of women developing knee osteoarthritis in their lifetimes. Osteoarthritis accounts for over 1 million U.S. hospitalizations annually, 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 developing Allocetra, a universal, off-the-shelf cell therapy designed to reprogram macrophages into their homeostatic state.