Drug Development


Why do diseases like OA remain an unmet need?

Successful treatment and management of disease or injury involving inflammation remains a great challenge in modern medicine. Numerous types of immune and structural cells are involved, and the pathways are networked and complex. There is consensus that this area may not be resolved with single target drugs as there are numerous classes of immune system cells involved, and the pathways are networked and complex.

What OA treatments exist?

There are currently a number of registered medicines and therapeutic goods for the treatment of osteoarthritis (OA), including oral non-steroidal anti-inflammatory drugs (NSAIDs) and intra-articular injections of hyaluronic acid or corticosteroids, as well as complementary medicines (which are not assessed by regulatory authorities for efficacy). Global guidelines recommend exercise and physiotherapy as first-line treatments, and topical and oral NSAIDs are considered the most effective available first-line pharmacological agents to manage pain associated with OA. However, to date, several meta-analyses of safety and efficacy studies have indicated only a small improvement in pain associated with NSAID use, and highlight the adverse effects of oral NSAIDs, particularly with chronic use. 1,2

Why is Paradigm developing PPS for OA?

Paradigm is responding to a growing need for new, safe, and effective treatments for diseases where there is high unmet need. Osteoarthritis (OA) affects millions of people globally and for many people the available therapies do not manage their symptoms for the long-term, and long-term use may also be associated with adverse effects. Additionally, there are no treatments approved that can prevent, stop, or restrain the progression of OA.

Paradigm’s clinical program in OA is investigating the use of injectable PPS to improve pain and function in patients with OA of the knee, as well as exploring the potential of PPS to modify progression of the disease. 1,2

Why the need for alternatives to opioids for the treatment of OA?

Concerns over the use of opioids have been well documented and PPS may have potential to reduce opioid use in osteoarthritis (OA). One of the highest priorities of the FDA is advancing efforts to address the crisis of misuse and abuse of opioid drugs harming families.1

The world’s leading medical societies for treatment and prevention of now strongly recommend against the use of opioids for the treatment of chronic pain in OA, citing harms which clearly outweigh benefits, and low-quality evidence to support their use.2,3 Despite these measures, opioids continue to be prescribed for the treatment of moderate to severe pain in people with OA who have not responded to other treatments. Therein lies the unmet medical need for people suffering from osteoarthritis: a treatment for the chronic pain and joint stiffness of osteoarthritis which is both safe and effective.

To date, PPS has a tolerable safety profile in clinical trials, and has promising signals of effectiveness from a phase 2 trial. Over 700 people have been treated via the TGA Special Access Scheme and FDA Early Access Program. PPS has the potential to reduce opioid use for the treatment of chronic pain and joint stiffness arising from OA.

How big is the opioid problem?

The problems arising from the prescription of opioids for chronic conditions are particularly pronounced in the United States. Almost 30% of patients with arthritis were treated with prescription opioids in 20131and over 16,000 deaths from prescription opioid use were reported in 2020.2

The US Department of Health and Human Services has declared the opioid “crisis” a national public health emergency and one of the highest priorities of the FDA is advancing efforts to address the crisis of misuse and abuse of opioid drugs.3

While the opioid problem is not as pronounced in Australia, between 2011-2015 there were 2,145 deaths associated with pharmaceutical opioids.4 It is currently estimated approximately 10% of all opioids prescribed within Australia are prescribed for OA pain, with opioids prescribed in 20% of general practitioner visits for hip OA, and 10% of visits for knee OA. Based on recent trends, it is forecast that by 2025, over 500,000 of 2.7 million Australians with OA will take opioids for OA management.5

Is PPS just being investigated for OA?

The potential effectiveness of pentosan polysulfate sodium (PPS) in a broad range of therapeutic areas can be explained by its ability to inhibit multiple biological processes that lead to the development of chronic diseases. The actions of PPS and its biological targets have been described in several peer-reviewed scientific publications.

Inflammation, tissue damage and adverse tissue remodelling are biological processes associated with chronic diseases such as osteoarthritis (OA), musculoskeletal symptoms of mucopolysaccharidosis (MPS), arthralgia associated with alphavirus infections such as Ross River (RRV) and chikungunya (CHIKV) viruses, heart failure (HF), and respiratory diseases such as acute respiratory distress syndrome (ARDS), allergic rhinitis (AR, hay fever), and asthma.

Currently Paradigm’s target indications for PPS include the treatment of joint functional impairment, mobility issues and pain in patients with OA and MPS (initially types I and VI). Paradigm has also completed phase 2 studies in AR and RRV as well as proof-of-concept pre-clinical studies in CHIKV, HF, and ARDS.
For the most recent updates on our progress and development, please see our ASX announcements.

How does OA develop?

Osteoarthritis (OA) is a disease of the whole joint, leading to and perpetuating inflammation, cartilage degeneration, vascular changes, and pain.

During inflammation triggered by OA, pro-inflammatory cells release cytokines, such as tumour necrosis factor alpha (TNF-α), and interleukin-1 beta (IL-1ß). These cytokines trigger a broad range of effects, including activating the lining of blood vessels to increase the number of pro-inflammatory cells at the site of injury, which in turn induces inflammation, pain and cartilage destruction.

We are investigating the potential of PPS to break the cycle of disease in OA.

Does Paradigm have exclusive rights to PPS?

Paradigm has an exclusive supply and licence agreement with the only FDA-approved PPS supplier, bene pharmaChem, extending for 25 years post registration.

The agreement covers all markets, ensures scalable manufacturing capabilities, and has been agreed for 25 years from date of marketing approval.

Plus, by working closely with the proprietary manufacturer of PPS, we are able to leverage substantial knowledge and expertise available from earlier regulatory filings.