In welcome news for suffers of knee-related osteoarthritis (OA), Paradigm Biopharmaceuticals Ltd (ASX:PAR) may have demonstrated a way to slow progression of the difficult-to-treat disease, which is currently managed with physiotherapy, corticosteroid injections and painkillers.
Data from Day 168 of the company’s clinical trial has indicated multiple signs that injectable pentosan polysulfate sodium (iPPS) may slow disease progression in knee osteoarthritis, meaning it may be a disease-modifying OA drug (DMOAD).
The DMOAD potential of iPPS is supported by changes and trends in four key biomarkers – ARGS, COMP, C2C and CTX-II – which were all reduced by Day 168 compared to placebo.
Structural changes in several disease features measured by magnetic resonance imaging (MRI) also pointed to a potential disease-modifying effect, specifically:
- 21% improvement in mean cartilage loss score compared to 4% worsening in placebo group;
- Statistically significant reductions in bone marrow oedema lesions compared to placebo; and
- Reduction of marginal osteophytes (bone spurs) compared to increases in the placebo group.
“We are seeing clinical and biomarker responses in both iPPS treatment groups over the 168-day study period,” Paradigm Biopharmaceuticals chief medical officer Dr Donna Skerrett said.
“Although many of the clinical responses are stronger in the twice-weekly group, biomarker and MRI responses are present in both iPPS groups.
“Given the small sample sizes in this study, variability is expected however the signals we have identified are consistent and concordant and support DMOAD mechanisms.
“Moving forward we will work to establish the clinical and regulatory characterisation of these findings for defining the DMOAD pathway for iPPS in order to confirm these findings in our larger clinical trial program.”
Apart from the physical changes noted during the trial, patients also experienced positive changes to their WOMAC pain, function, stiffness and overall scores.
Apart from ongoing lessening of pain, the average number of days participants used rescue medication was four times higher in the placebo group (23 days) compared to the twice-weekly iPPS group (5 days) at Day 168.
Likely to support partnering discussions
“A non-opioid drug for treating the symptoms of osteoarthritis (pain and joint stiffness) with durability of effect out to 168 days (6 months) plus signals of disease-modifying potential, is well poised to address a major unmet medical need,” Paradigm Biopharmaceuticals managing director and chair Paul Rennie said.
“These data are expected to assist our partnering discussions.”
PAR will present its new MRI, molecular biomarker and clinical outcomes to the Regulatory Authorities (FDA and EMA) and seek their input as to what additional data will be needed from a larger controlled study for iPPS to obtain a DMOAD label.
The company also hosted an investor webinar at 9:30 am AEST, to present and discuss data from the trial.