Animal drug could be repurposed to help osteoarthritis sufferers
Millions of osteoarthritis sufferers across the world could soon benefit from a pain relief drug currently used to treat joint issues in horses, cats, dogs and even racing camels.
Australian late-stage clinical development company Paradigm Biopharma is investigating injectable pentosan polysulfate sodium (iPPS) as a potential disease-modifying treatment for knee osteoarthritis (KOA).
The plant-derived, semi-synthetic drug has been used in the veterinary space for over 80 years to improve joint health and preserve cartilage integrity. It is registered for use by vets in more than 20 countries.
Until now, pentosan polysulfate sodium has only been used in humans over the age of 16 to treat blood clots and the discomfort or bladder pain associated with interstitial cystitis.
However, a number of current and former Australian Football League (AFL) players have been using Paradigm’s iPPS under a Special Access Scheme (SAS). This is a programme set up by the Therapeutic Goods Administration (TGA) for doctors to prescribe medications that are not listed on the Australian Register of Therapeutic Goods (ARTG).
After being repurposed and provided via subcutaneous injections in various trials, Paradigm has said the drug’s capabilities are proving to be more applicable in treating osteoarthritis, caused by the breakdown of cartilage in joints.
Now the company aims to bring hope to the estimated half a billion osteoarthritis sufferers around the world – 70% of whom are affected by the degenerative joint disease in the hip or knee.
There are currently no disease-modifying osteoarthritis drugs approved for the treatment of KOA. Instead non-steroidal anti-inflammatory drugs, analgesics and glucocorticoid injections are commonly prescribed for treatment.
But each of these drugs only deal with the symptoms, leaving the underlying degenerative problems untreated.
With osteoarthritis expected to become the single greatest cause of disability globally by 2030, there is a considerable unmet medical need for a disease-modifying drug.
Paradigm, which has its head office in Melbourne, Victoria, is focused on improving patients’ health and quality of life through the development of known therapeutics to address unmet medical needs in conditions where sustained inflammation is present.
People with osteoarthritis need alternative therapeutic solutions, as the current treatments often don’t provide sufficient relief, leaving them in pain and with a reduced quality of life.
Former Geelong, Sydney Swans’ and Carlton AFL player, Greg ‘Diesel’ Williams, 59, understands only too well how knee OA can have a devastating impact on your life.
Greg, who played AFL for 14 years during the 1980s and 1990s and is a dual Brownlow Medal winner who at his peak was the then-highest-paid player in the history of the sport, suffers with severe knee OA. A one-time world class athlete, he now can’t run, and has difficulty walking. 
He explained: “If you’ve got OA people really don’t understand what we’re going through. It’s so painful. It’s so sore. It’s so, so hard to put up with. And it’s about time we did something about it.”
He has tried all kinds of medication, and spoken with the best surgeons, but is still in severe pain with KOA. He added: “If I could find a solution that’s medical, not surgical, yeah, I’d be going for that 100mph.”
As yet he doesn’t want to go down the path of having a knee replacement. “I may have stopped playing, but I don’t want to stop living,” he said.
Dr Philip Bloom, a specialist sports physician with over 20 years’ experience and specialist training in treating and managing musculoskeletal injuries and diseases to maximise function, explained: “Osteoarthritis of the knee is not just an isolated pain in the knee. It has a trickle-down effect on the rest of your life, particularly in regards to losing the ability to be active, which causes obesity, more aches and pains in other joints, and also psychological problems such as depression and anxiety.”
Whilst anyone can get osteoarthritis, most cases affect adults over the age of 45 and it is a major cause of disability in people aged 65 and over. Women are more likely than men to suffer from the condition – often referred to as ‘wear and tear’ arthritis – especially after the age of 50.
Results from a six-month long phase 2 trial run by Paradigm Biopharma have already shown that iPPS may slow the progression of KOA.
The exploratory 61-patient phase 2 randomised, double blind, placebo-controlled trial for synovial biomarkers in knee osteoarthritis showed changes consistent with disease modifying efficacy in subjects with moderate to severe osteoarthritis. Seventy eight per cent of subjects had moderate to severe osteoarthritis of the knee.
The six-month data indicated disease modifying potential for the drug in KOA based on less cartilage loss, as measured by MRI, in the iPPS group compared to those on placebo. MRIs of the placebo group cartilage showed an increase in its loss.
Levels of synovial biomarkers of cartilage and aggrecan disintegration 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 is now undertaking a comprehensive global phase 3 clinical trial designed to maximise the potential of iPPS, which it will market under the name Zilosul.
To this end the company has launched a clinical trial website to facilitate current and potential trial participants and support its development programme for KOA therapy called Hope4OA.com.
Here people living in either Australia or the US, can put their name forward as a potential trial participant, and find the answers to commonly asked KOA questions alongside patient support.
