Top-line phase 2 trial data shows disease modifying potential and pain reduction
MELBOURNE, Australia, April 11, 2023 (GLOBE NEWSWIRE) -- Australia’s Paradigm Biopharmaceuticals Ltd (ASX:PAR) says analysis of six-month trial data shows injectable pentosan polysulfate sodium (iPPS) may slow the progression of osteoarthritis of the knee.
In October 2022, Paradigm said its phase 2 clinical study met its primary endpoint of a change from baseline to day 56 in one or more osteoarthritis disease biomarkers in synovial fluid.
In addition to reaching the primary endpoint, clinical scores using the Western Ontario McMaster Universities Arthritis Index (WOMAC) of pain and function at day 56 were statistically significant.
The change from baseline to day 56 for pain and function are the approved endpoints in Paradigm’s 300-patient global phase 3 trial currently recruiting in the US, Europe and Australia.
The remainder of the Phase 2 clinical trial was exploratory and aimed to investigate if iPPS could improve bone and cartilage as measured by magnetic resonance imaging (MRI) at the early point of six months. Pain and function were also measured at six months. Paradigm said the effect of the drug was sustained at the six-month time point.
There are currently no approved treatments for knee osteoarthritis that stop or slow the disease.
The exploratory 61-patient phase 2 randomised, double blind, placebo-controlled trial of iPPS for synovial biomarkers in knee osteoarthritis showed changes consistent with disease modifying efficacy in subjects with moderate to severe osteoarthritis. 78% of subjects had moderate to severe osteoarthritis of the knee.
The study was not powered for statistical significance and a 12-month data analysis will be released at the end of 2023.
The six-month data indicates disease modifying potential for the drug in knee osteoarthritis based on less cartilage loss, as measured by MRI, in the iPPS group compared to the placebo group. MRIs of the placebo group cartilage showed an increase in cartilage loss.
Levels of synovial biomarkers of cartilage and aggrecan breakdown (ARGS, COMP, C2C, and CTX-II) were down at six months in the iPPS group. The same biomarkers increased in the placebo group.
Statistically significant reductions in bone marrow lesions, measured by MRI, were seen compared to placebo, with a trend towards reduced marginal osteophytes (bone spurs) compared to an increase in the placebo group.
Paradigm said analysis of results also showed persistent positive clinical responses in the universally used WOMAC pain and function scores from a single 6-week treatment course, with noticeable positive trends and durable effects out to six months.
Following a short six-week course of once- or twice-weekly under-skin injections with either the study drug or placebo, volunteers with moderate to severe knee osteoarthritis underwent multiple clinical and laboratory investigations at eight weeks and again at six months from the start of treatment.
High-resolution magnetic resonance imaging of patient knees showed cartilage degradation may be slowed or even reversed.
Paradigm Biopharmaceuticals Managing Director Paul Rennie said, “A non-opioid drug for treating the symptoms of osteoarthritis with durability of effect out to six months, plus signals of disease modifying potential, is well poised to address a major unmet medical need.”
Mr Rennie said Paradigm would initiate discussions with key drug regulatory agencies in the US and Europe in order to reach agreement on disease modification label pathways for iPPS.
Mr Rennie said the data would assist partnering discussions and Paradigm was now working to establish a clinical and regulatory pathway for the drug, “Understanding the key requirements needed by regulatory bodies to evaluate a disease-modifying OA drug is crucial to creating a novel approval pathway that currently doesn’t exist.”
Paradigm is enrolling patients in a global phase 3 trial to identify the optimal dose in knee osteoarthritis as well as confirm clinical effectiveness along with continued safety studies.
The Australian New Zealand Clinical Trials Registry anzctr.org.au reference for the study is ACTRN12621000136808. The primary endpoint is a change from baseline at day 56 in WOMAC pain and function. For US residents, more information can be found at www.hope4oa.com.
Pentosan polysulfate sodium (PPS) was discovered as an anticoagulant 60 years ago. It was approved by the US Food and Drug Administration in 1996 as a tablet to manage bladder inflammation.
Paradigm’s complete ASX announcement can be read HERE.
For more information please contact:
In Australia – Simon White firstname.lastname@example.org +61 (0) 404 216 467
International – Sue Charles Sue.email@example.com +44 (0)7968 726585
About Paradigm Biopharma
Paradigm Biopharmaceuticals Ltd. (ASX:PAR) is a late-stage drug development company driven by a purpose to improve patients’ health and quality of life by discovering, developing, and delivering pharmaceutical therapies. Paradigm’s current focus is developing injectable (subcutaneous) pentosan polysulfate sodium (iPPS) for the treatment of diseases where inflammation plays a major pathogenic role, indicating a need for the anti-inflammatory and tissue regenerative properties of PPS, such as in osteoarthritis (phase 3) and mucopolysaccharidosis (phase 2).