Addressing an unmet need

Successful treatment and management of conditions involving inflammation remains a great challenge in modern medicine, as there are numerous types of immune and structural cells involved, and the pathways are networked and complex.

Paradigm is responding to a growing need for effective, safe treatments for our targeted clinical indications, where there are currently limited options available to patients. Our clinical trial in the use of PPS to treat patients with osteoarthritis of the knee and subchondral bone marrow lesions is a case in point.

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 corticosteroids, as well as complementary medicines (which are not assessed by regulatory authorities for efficacy). NSAIDs are considered the most effective available first-line therapeutic agent to manage pain associated with OA (1). 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, particularly with chronic use. (1) (2) (3) (4)

In addition to these, in recent years there has been a trend towards the prescription of weak and strong opioids for the treatment of moderate to severe pain in people with hip or knee OA who have not responded to other analgesic medications or NSAIDs. (1) (5)

There are now strong recommendations against the use of prescription opioids for the treatment of chronic pain in OA, citing harms which clearly outweigh benefits, and low-quality evidence to support their use (1).

The RACGP’s revised 2018 recommendation comes at a time of increasing awareness of the significant potential for harm from long term use of opioids (including dependence, overdose and death), lack of evidence to support long term efficacy, and potential for tolerance or increased pain perception with long term use.

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 2013 (5). This trend coincides with strong concerns about their safety. In 2016 17,087 prescription opioid deaths were reported (6), and in 2017, the US Department of Health and Human Services officially declared the opioid “crisis” a national public health emergency.

While the opioid problem is not as pronounced in Australia, between 2011-2015 there were 2145 deaths associated with pharmaceutical opioids (7). 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 (8).

Paradigm recognises the pressing need for new, safe and effective treatments for the pain and symptoms of OA, and it is our hope that PPS may be a very strong candidate in this field.


1. RACGP. Guideline for the management of knee and hip OA 2nd edition. Melbourne : The Royal Australian College of General Practitioners, 2018.

2. Non-steroidal anti-inflammatory drugs, including cyclo-oxygenase-2 inhibitors, in osteoarthritic knee pain: meta-analysis of randomised placebo controlled trials. al, Bjordal JM et. Trodheim : BMJ, 2004, Vol. 328.

3. A turbulent decade for NSAIDs – update on current concepts of classification, epidemiology, comparative efficacy and toxicity. P.G, Conaghan. Leeds, UK : Rheumatol Int, 2012, Vol. 32.

4. Chou R. et. al, Analgesics for Osteoarthritis: An Update of the 2006 Comparative Effectiveness Review. Comparative Effectiveness review No 38. Rockville, US: Agency for Healthcare Research and Quality, 2011. Vol. 38.

5. Prevalence and Trends in prescribed opioid use among US adults with arthritis, 2008-2013, medical expenditure panel survey. Hootman, J. s.l. : American College of Rheumatology, 2016.

6. (CDC), Centre for Disease Control and Prevention. Prescription Opioid data. [Online] 2018. [Cited: Sep 18, 2018.]

7. TGA. Consultation Paper: Prescription of strong (Schedule 8) opioid use and misuse in Australia –options for a regulatory response. ACT: TGA, 2018.

8. Forecasting the future burden of opioids for osteoarthritis. Ackerman. 2018, Osteoarthritis and Cartilage, Vol. 26, pp. 350-355.