Apoptotic Cell Therapy Shows Promising Benefits for Older Adults With Knee OA, with Philip Conaghan, MBBS, PhD

Apoptopic cell therapy (Enlivex Therapeutics) has demonstrated promising safety and efficacy in older adults over the age of 60 with moderate-to-severe knee osteoarthritis.

The cell therapy was evaluated in the multicenter, randomized, double-blind, placebo-controlled phase 2a ENX-CL-05-001 trial (NCT06233474), findings from which were presented by Philip Conaghan, MBBS, PhD, Director, NIHR Leeds Biomedical Research Centre, and Professor of Musculoskeletal Medicine at University of Leeds at the American College of Rheumatology (ACR) Convergence 2025, held October 24–29 in Chicago, Illinois.

The study enrolled 129 patients with Kellgren-Lawrence grade 2–3 disease, who received 3 knee injections over 28 days and were followed for 12 months. Conaghan and colleagues found that numerical rating scale (NRS) pain improvement was 24% higher with apoptotic cell therapy than placebo, and WOMAC pain and function improvements were also numerically higher than placebo, however, these did not reach statistical significance. A predefined age-related responder group (≥60 years; 53.5% of participants) did demonstrate clear benefits with apoptotic cell therapy.

At 3 months, patients aged 60 and older reported a 72% relative improvement in WOMAC pain (–27.82 vs –16.22; P = .03), a 109% improvement in function (–26.45 vs –12.63; P = .007), and a 92% improvement in total WOMAC score (P = .012) compared with placebo. For patients ≥65 years, effects were even more pronounced, with the total WOMAC improvement reaching –27.14 vs –6.03 (P = .0004). These clinically meaningful benefits were accompanied by consistent trends in NRS pain reduction and durability through month 6.

In terms of safety, there were some adverse events, mostly transient effusions, after injection that were more frequent with apoptotic cell therapy (89.6%; n = 60) than placebo (71.6%; n = 48%).

HCPLive spoke with Conaghan to learn more about the potential of apoptotic cell therapy to provide a therapeutic benefit for knee OA, the importance of age- and phenotype-driven targeting, and how the field may finally be moving closer to precision therapy for osteoarthritis.

"I think a problem for all OA trials has been finding the subgroup, the phenotype, or the endotype, that might be responsive to a given therapy, and that's thought to be the reason why certain therapies haven't worked. So this was interesting that there's a very strong age signal," Conaghan said.

Reference

Conaghan P, Husøy B, Rovsing C, et al. Randomized, Double-Blind, Placebo-Controlled Phase IIa Trial of an Innovative Intra-Articular Apoptotic Cell Therapy in Knee Osteoarthritis (OA): 3-Month Positive Outcomes and Identification of Responder Population (NCT06233474). Presented at: ACR Convergence 2025; October 24-29; Chicago, Illinois. Poster #LB12