Paradigm Biopharmaceuticals (ASX: PAR) has reported a breakthrough in its phase 2 clinical trial of the injectable pentosan polysulfate (iPPS) treatment drug Zilosul, showing it could act as a cartilage-protective agent and slow cartilage degradation in patients with progressive osteoarthritis of the knee.
The trial has demonstrated a significant reduction in the levels of two key biomarkers – cartilage oligomeric matrix protein (COMP) and ADAMTS-5 – which are associated with cartilage degradation and elevated in the serum of people with advancing osteoarthritis.
During the trial, the levels of COMP in the serum of patients treated with the iPPS showed a mean percentage reduction of 11.9% from baseline at day one to day 53, compared to the placebo group which showed a mean percentage increase of 2.1%.
In parallel, ADAMTS-5 – the key enzyme involved in the degradation of aggrecan in cartilage – showed a mean percentage reduction of 5.1% in the serum of iPPS-treated subjects compared to a mean percentage increase of 10% in the placebo group.
COMP and ADAMTS-5 reside in the cartilage and are considered reliable indicators of progressively-worsening osteoarthritis.
As the cartilage around the joint breaks down, the biomarkers are released into the blood.
Patients with elevated levels of these biomarkers in their blood are diagnosed as having an increased level of cartilage degeneration which is the hallmark of progressive osteoarthritis.
The trial data supports iPPS as a cartilage-protective agent which could potentially block the progression of knee osteoarthritis.
Paradigm said the “groundbreaking discovery” suggests that using Zilosul can protect cartilage from progressive degradation as well as reduce pain and improve joint function in osteoarthritic patients.
“It appears to indicate that treatment with Zilosul protects, slows or stops the cartilage around the joint from degrading – slowing the progression of the disease,” it said.
“It adds to the clinical evidence that Zilosul could materially impact the progression of a disease that previously was thought to have no effective disease modifying treatment options.”
Paradigm is expecting the release of more biomarker data in the coming months.
A biomarker is a naturally occurring molecule, gene, or characteristic by which a particular pathological or physiological process or disease can be identified.
In the case of progressive osteoarthritis, several molecules are released from the bone and are known to be associated with the breakdown of cartilage.
COMP is the biomarker which is the most investigated to predict knee osteoarthritis progression.
ADAMTS-5 (or A disintegrin and metalloproteinase with thrombospondin motifs-5) is the main enzyme which degrades aggrecan – a major component found in animal and human osteoarthritis articular cartilage.
The loss of COMP and ADAMTS-5 from cartilage – without the compensatory synthesis of new macromolecules to replace those lost through the process – can significantly compromise the biomechanical strength of articular cartilage, leading to its degradation.
At mid-morning, shares in Paradigm were up 14.58% to $1.65.