LMWF-5A for the Treatment of Severe Osteoarthritis of the Knee: Integrated Analysis of Safety and Efficacy

Abstract

The low-molecular-weight fraction of 5% human serum albumin (LMWF-5A) is being developed to treat the signs and symptoms of severe osteoarthritis of the knee. This study was a post hoc pooled analysis of 3 randomized placebo-controlled trials of a single intra-articular injection of LMWF-5A, focusing on the subset of patients with severe osteoarthritis of the knee (Kellgren-Lawrence grade 4). Patients were randomized 1:1 to receive a single 4-mL intra-articular knee injection of either LMWF-5A or saline. Safety was assessed as the incidence and severity of adverse events. Efficacy was assessed as the change from baseline to week 12 on the Western Ontario and McMaster Universities Osteoarthritis Index pain (primary outcome), stiffness, and physical function subscores and on patient global assessment scores and was presented as the least squares mean difference and 95% confidence interval. The proportion of responders was defined with the Outcome Measures in Rheumatology-Osteoarthritis Research Society International criteria for scenario D and examined with Pearson's chi-square test. For 417 patients with severe osteoarthritis of the knee, treatment with LMWF-5A resulted in a significant decrease in pain at 12 weeks compared with saline (mean difference, -0.19; 95% confidence interval, -0.34 to -0.04; P=.016), with improvements in function (mean difference, -0.15; 95% confidence interval, -0.31 to 0.01) and patient global assessment (mean difference, -0.30; 95% confidence interval, -0.49 to -0.12) and higher responder rates (64.25% vs 50.90%, P=.006). No drug-related serious adverse events and no deaths occurred, and the incidence and severity of adverse events were similar across treatment groups. This pooled analysis supports the use of LMWF-5A as a safe therapeutic agent for relief of the signs and symptoms of severe osteoarthritis of the knee. [Orthopedics. 2018; 41(1):e77-e83.].

Intra-articular treatment options for knee osteoarthritis

“…LMWF-5A (Ampion) is an injectable, low molecular weight fraction of 5% human serum albumin that is currently being developed by Ampio Pharmaceuticals (Englewood, FL, USA). The primary constituent of LMWF-5A, artyl-alanyl diketopiperazine, modulated the inflammatory immune response in vitro through a pathway in which T cells were implicated 144 , and several clinical studies have been published in which the effects of LMWF-5A on knee OA were investigated 145–147 .…”

“…Overall, the available data suggests that the short­term effects of LMWF-5A may be non-inferior (although not likely to be superior) to currently used intra-articular treatment modalities. The long-term effects of LMWF-5A have yet to be determined, but the results of in vitro studies 144,148 and of a post hoc analysis 147 are encouraging. An open label, phase III extension study to evaluate the long-term safety of LMWF-5A is currently underway 149 .…”

On the Mechanisms of Action of the Low Molecular Weight Fraction of Commercial Human Serum Albumin in Osteoarthritis

“…Furthermore, the described biochemical reactions are elicited by unique drug components and are independent of the formulation buffer. This may help explain why the effect of LMWF5A was markedly better than that of saline when function and quality of life, as well as reduction of pain, were the trial endpoints considered in the most severe cases of OAK [2, 3].…”

Emerging Trend in the Pharmacotherapy of Osteoarthritis

“…A clinical trial of 329 patients with moderate to severe OA under the treatment of Ampion™ over 12 weeks resulted in a significant reduction in WOMAC pain compared to vehicle control (60). Analysis of 3 randomized placebo-controlled trials of 417 patients with severe knee OA (Kellgren-Lawrence grade 4) indicated that Ampion™ significantly improved WOMAC pain, physical function, and patient global assessment scores and higher responder rates compared with saline (63). No severe drug-related deaths or withdrawals associated with adverse events during the HSA treatment have been reported to date and additional long-term clinical trials are required to further determine its clinical benefit.…”