Allocetra Immunotherapy Gets RMAT Designation for Age-Related Knee Osteoarthritis

The US Food and Drug Administration (FDA) has granted Regenerative Medicine Advanced Therapy (RMAT) designation to Allocetra (Enlivex Ltd.) for the treatment of age-related symptomatic primary knee osteoarthritis (OA) in adults aged 64 and older, Enlivex announced July 13, 2026.¹ The designation, supported by Phase I/IIa trial data showing statistically significant reductions in knee pain and improvement in physical function versus placebo sustained through 6 months, is intended to expedite development and review through intensive early FDA engagement and eligibility for accelerated approval and priority review pathways. Allocetra is not approved for any indication.

Osteoarthritis affects more than 32 million Americans currently and is projected to affect approximately 78 million by 2040. No disease-modifying pharmacologic therapy has been approved for OA in any joint; management remains primarily symptomatic through NSAIDs, intra-articular corticosteroids, and ultimately joint replacement surgery.

Allocetra - Allogeneic Cell Therapy

Allocetra is an allogeneic cell therapy comprising donor-derived apoptotic mononuclear cells that reprogram macrophage activity at the site of joint inflammation. Rather than broadly suppressing inflammation, the therapy is designed to shift synovial macrophages from a pro-inflammatory to a homeostatic phenotype — a mechanism Enlivex characterizes as macrophage reprogramming immunotherapy. In OA, synovial macrophage dysfunction is increasingly recognized as a driver of cartilage degradation and persistent joint inflammation.¹

72% Reduction in Pain Versus Placebo

The RMAT designation was based on results from a multi-center, randomized, Phase I/IIa trial (NCT06233474; ENX-CL-05-001) evaluating single intra-articular injections of Allocetra versus placebo in patients with moderate-to-severe knee OA. In the prespecified primary age-related subgroup of patients aged 60 and older — identified as the population demonstrating the most pronounced treatment effect — 3-month topline data reported in August 2025 showed a 72% reduction in pain versus placebo and a 109% improvement in function versus placebo, both exceeding prespecified FDA thresholds for Phase III advancement.² Six-month follow-up data, reported in November 2025 and presented orally at the European Alliance of Associations for Rheumatology (EULAR) 2026 European Congress of Rheumatology in June 2026 by Philip Conaghan, MBBS, PhD, confirmed durability of both pain and functional improvements through the end of the observation period.² ³

"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 told RheumatologyLive in an earlier interview.

Clinicians should note that the efficacy figures are from topline data that have not yet been published in a peer-reviewed journal; the identified age-related responder population was defined post hoc based on observed treatment effect, and the narrowing of the Phase IIb eligibility criterion from age ≥60 to age ≥64 reflects both that responder analysis and regulatory input. No drug-related serious adverse events were reported in the Phase I/IIa program; observed reactions were predominantly mild-to-moderate, transient local injection site events.²

Topline Phase 2b Data Expected in 2027

Based on these data, Enlivex has initiated a randomized, controlled Phase IIb trial enrolling 182 patients aged 64 and older with primary age-related knee OA across US and EU sites; the first US patient was dosed prior to today's announcement.¹ Topline data from the Phase IIb trial are expected by the end of the second quarter of 2027. In connection with the RMAT designation, the FDA has requested a Type B meeting with Enlivex to conduct a comprehensive, multidisciplinary review of the Allocetra development program and align on Phase IIb and pivotal trial parameters.¹

References

1. Enlivex Ltd. Enlivex receives FDA Regenerative Medicine Advanced Therapy (RMAT) designation for Allocetra in age-related knee osteoarthritis. Press release. July 13, 2026. https://www.globenewswire.com/news-release/2026/07/13/3326135/0/en/enlivex-receives-fda-regenerative-medicine-advanced-therapy-rmat-designation-for-allocetra-in-age-related-knee-osteoarthritis.html

2. Enlivex Ltd. Enlivex announces positive 6-month topline data demonstrating durable and persistent pain reduction and improved function in primary age-related patients with moderate to severe knee osteoarthritis. Press release. November 24, 2025. https://enlivex.com/investors/news-releases/enlivex-announces-positive-6-month-topline-data-demonstrating-durable-and-persistent-pain-reduction-and-improved-function-in-primary-age-related-patients-with-moderate-to-severe-knee-osteoarthritis/

3. Callagahn PG, Husøy B, Rovsing C, et al. DURABLE EFFICACY AT 6 MONTHS USING AN INNOVATIVE INTRA-ARTICULAR APOPTOTIC CELL THERAPY IN KNEE OSTEOARTHRITIS: DATA FROM A PHASE IIA RCT. Oral presentation at: EULAR European Congress of Rheumatology; June 3–7, 2026; London, UK. #OP060