TPX-100 shows 'statistically significant' decrease in bone shape change in knee OA
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TPX-100, a novel 23-amino acid peptide, has a “significant effect” on bone shape, as measured by B-score, in knee osteoarthritis and shows promise as a disease-modifying drug, according to data published in Arthritis Research & Therapy.
“TPX-100 is a 23-amino acid peptide derived from matrix extracellular phosphoglycoprotein (MEPE), a small integrin-binding ligand N-linked glycoprotein (SIBLING) family member,” Dawn McGuire, MD, FAAN, chief medical officer of OrthoTrophix, in Foster City, California, and colleagues wrote. “MEPE is highly expressed by osteocytes, is downregulated in osteoarthritis, and may play a role in osteoarthritic bone remodeling. TPX-100 has been shown to induce articular cartilage formation in vitro and in vivo.”
“Bone shape change, measured by MRI, has been shown to predict radiographic onset of OA, is associated with radiographic structural progression, discriminates people with knee OA from those without knee OA, and is more responsive to change over time than is radiographic assessment,” they added. “The femoral bone shape (‘B-score’) metric is a form of statistical z-score that represents the position of a femoral bone shape along a shape vector from a non-OA knee shape (origin) toward an OA knee shape (positive direction).”
To compare MRI 3D femoral bone shape changes, or B-scores, in patients treated with either intra-articular TPX-100 (OrthoTrophix) or placebo, and analyze the link between cartilage thickness and bone shape change over 1 year, McGuire and colleagues conducted a retrospective study of data in the TPX-100-1 trial. In that trial, 104 patients aged between 25 and 75 years with bilateral patellofemoral knee OA were enrolled at 15 sites across the United States. For each participant, one knee was randomly assigned to receive 4 weekly injections of TPX-100 in doses of 200 mg, while the contralateral knee received a placebo.
For their retrospective study, McGuire and colleagues analyzed 93 of the previous trial’s participants, after excluding those who were lost to follow-up, discontinued the intervention, had missing MRI data or received only one dose. After additional MRI quality control, a total of 78 participants — a total of 156 knees — were included for analysis, with 15 disqualified due to image quality. Images were evaluated for quantitative femoral B-score and cartilage thickness, with all analyses performed centrally, blind to treatment assignment and clinical data.
According to the researchers, knees treated with TPX-100 demonstrated a statistically significant decrease in pathologic bone shape change (0.0298; 95% CI, –0.037 to 0.097), compared with placebo knees (0.1246; 95% CI 0.067-0.182), at 6 months. Results remained statistically significant at 12 months, at 0.0856 (95% CI, 0.013-0.158) and 0.1969 (95% CI, 0.123-0.271), respectively.
In addition, the correlation between 12-month bone shape change and medial and total tibiofemoral cartilage thickness changes was statistically significant in knees that received TPX-100 (P < 0.01).
“These data represent, to our knowledge, the first report of an investigational agent demonstrating a significant treatment difference compared with placebo on pathologic bone shape (B-score) change in the knee,” McGuire and colleagues wrote. “These results of structural imaging in TPX-100-treated knees compared with placebo-exposed knees, in combination with previously reported robust improvements in established clinical outcomes (as measured by WOMAC and KOOS scores), support the potential of TPX-100 as a candidate disease-modifying drug in knee OA.”
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