Paradigm Biopharmaceuticals Ltd (ASX:PAR) is trading higher after achieving the primary endpoint of its PARA_OA_008 Synovial Fluid Biomarker Phase 2 clinical trial, assessing the effect of injectable Pentosan Polysulfate Sodium (iPPS) on osteoarthritis (OA) biomarkers over time.
The company observed several biomarkers improving over time in those treated with iPPS compared to placebo, as well as statistically significant improvements in WOMAC pain, function and stiffness scores at day 56.
The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) is a widely used self-administered health status measure used in assessing pain, stiffness and function in patients with OA of the hip or knee.
During the trial, 73% of participants recorded a greater than 30% improvement in WOMAC pain scores, while 60% experienced a greater than 50% improvement.
Paradigm assessed biomarkers including nerve growth factor (NGF), tumour necrosis factor-alpha (TNF-α), Interleukin-6 (IL-6), COMP, Alanine-Arginine-Glycine-Serine (ARGS) and Tissue inhibitor of MMPs (TIMP-1) and observed positive corrections in each case with iPPS treatment.
The company says these biomarker changes provide insight into iPPS mechanisms of action as well as signalling its disease-modifying potential.
Investors have responded positively, sending shares as much as 21.43% higher this morning to A$1.535.
Trial results to guide regulatory pathway
"We are very encouraged by the synovial fluid biomarker signals we see in this study,” Paradigm Biopharmaceuticals chief medical officer Dr Donna Skerrett said.
“The observed changes indicate mechanistic effects through pain, inflammation and chondroprotective pathways. These changes are consistent with the clinical effects observed in this and prior studies of iPPS in osteoarthritis.
“Evidence of multimodal effects supports our understanding of the actions of iPPS. These biomarker changes in the joint, following subcutaneous administration of iPPS, demonstrate local effects in the synovial fluid.
“These are meaningful signals that we will evaluate together with clinical and imaging outcomes in order to demonstrate disease-modifying effects and to pursue regulatory authority guidance on a disease-modifying pathway."
PAR’s treatment has the potential to be the first established disease-modifying therapy for osteoarthritis, for which current treatments – paracetamol, opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids and hyaluronic acid injections – are solely designed for symptom management.
Results from canine model of OA
Paradigm has also been assessing the effect of iPPS on a canine model with naturally occurring OA.
Interim data has been generated for nine dogs treated subcutaneously with iPPS at a dose of 3 milligrams per kilogram for six weeks, demonstrating the following:
Seven of nine dogs had a clinically meaningful improvement in the affected limb as measured by total pressure index percentage (TPI%) at week 8 compared to baseline.
There was a 10.08% mean improvement from baseline in TPI% for the hindlimb and 5.6% improvement for the front limb, both clinically meaningful.
Overall:
- 3/6 dogs demonstrated a reduction in biomarker ARG;
- 5/9 showed a reduction in cartilage degradation markers;
- 7/9 iPPS-treated dogs responded to treatment with reduced levels of C3M (a degradation fragment of type III collagen);
- 6/9 dogs had lower levels of CTX-I (a degradation fragment of type I collagen); and,
- 4/9 dogs had reduced levels of CTX-II (a degradation product of type II collagen).