The US Food and Drug Administration (FDA) has cleared the company’s Investigational New Drug application to conduct registration studies in the US.
MELBOURNE, Australia: Paradigm Biopharmaceuticals, a company repurposing existing molecules for new indications with unmet clinical needs, says it will begin registration studies in the United States and Australia in coming weeks to evaluate its lead compound, Zilosul® (pentosan polysulphate sodium) for patients with knee osteoarthritis pain (kOA).
The US Food and Drug Administration (FDA) has cleared the company’s Investigational New Drug application to conduct registration studies in the US.
Enrolment at 65 US and Australian trial sites will begin in December with UK and European sites to follow in 2022.
The randomised, adaptive, double-blind, placebo-controlled, multicentre study called PAR_OA_002 will evaluate the dose and treatment effect of PPS compared to placebo in participants with kOA.
The primary endpoint is a reduction in pain at day 56 assessed by the Western Ontario and McMaster Universities (WOMAC) pain scale. WOMAC is a standard measure approved and used widely to assess osteoarthritis of the knee and hip including levels of pain, stiffness and function of the joints.
A Phase IIb trial, showed PPS reduced knee pain and improved function and reduced pain in patients with knee OA versus those who took placebo.
Phase III Lead Investigator Professor Thomas Schnitzer from Northwestern University in Chicago Illinois said, “We are pleased to evaluate PPS in people suffering from kOA in this clinical study and are hopeful we can approach the unmet need for treatments that decrease the severity and duration of their pain. The need for alternatives is particularly relevant given the challenges we face from the reliance on opioids, especially among people with chronic musculoskeletal pain.”
Paradigm CEO Paul Rennie said: “The opening of the Trial in the USA – the largest global pharmaceutical market, is a major milestone for the Company. This milestone represents a substantial de-risking of the Company’s lead clinical program and is a testament to the Company’s expertise, commitment and determination. As the Company progresses with the Trial, we expect there will be increasing interest from the pharmaceutical industry in the commercial value of this potential blockbuster therapeutic”.
Paradigm has offices in Australia, the UK and USA and is interested in exploring strategic partnerships for commercialisation of PPS as a treatment for osteoarthritis.
About injectable PPS
Pentosan polysulfate sodium (PPS) is a medication that has been used in humans for over 60 years. Injectable PPS has previously been approved in European markets, where it is registered as an antithrombotic agent. In Australia, injectable PPS for human use is not currently available for sale. Injectable PPS is available via a Paradigm sponsored clinical trial or under the TGA Special Access Scheme to physicians for individual patients who satisfy strict criteria and is subject to approval from the TGA. Elmiron (the oral formulation utilised for interstitial cystitis) is the only PPS product approved in the US. A subcutaneous injectable formulation of PPS is currently being evaluated by Paradigm for the treatment of osteoarthritis and other inflammatory diseases in the US and other major global markets.
Paradigm has a license to commercialise PPS with the manufacturer and patent owner Bene PharmaChem GmbH & Co for a broad range of diseases.
PPS is approved in oral form by the FDA and is sold by Janssen Pharmaceuticals, under the brand Elmiron®, for interstitial cystitis, a chronic inflammation of the bladder wall.
PPS is similar to heparin and works as an anti-blood clotting agent by inhibiting the action of an enzyme called activated factor Xa, which plays a key role in helping blood cells stick together in clotting.
Paradigm is repurposing PPS as a subcutaneous treatment to reduce pain and improve function in people with osteoarthritis of the knee (kOA), and has trademarked an injectable formulation of PPS as Zilosul®.
A phase IIb trial showed PPS reduced osteoarthritis knee pain and improved knee function. Injectable PPS is also widely used for the treatment of osteoarthritis in dogs and horses.
Researchers believe PPS is a strong potential candidate for the treatment of OA based on its multiple mechanisms of action, in-vitro and in-vivo (animal) studies demonstrate PPS:
Further work is underway to explore the potential of PPS as a disease modifying treatment for osteoarthritis.
Unmet need in OA
Current OA therapies such as paracetamol, opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) are focused on symptom management and there are no established disease modifying therapies in OA. Due to patient dissatisfaction with current treatment for OA there is a high unmet medical need for new therapies that are effective in reducing pain, improving joint function and impacting disease progression.
The prevalence of OA is increasing in line with the ageing population and increasing rates of obesity. By 2030 the number of people suffering from OA in the US is predicted to increase by 86% to 67 million. If we assume a similar increase across the other markets defined above, even allowing for lower rates of obesity in non-US markets, it is plausible that more than 120 million people will be suffering from osteoarthritis by 2030.
Paradigm is interested in exploring strategic partnerships for commercialisation of PPS as a treatment for osteoarthritis.
About the Trial (PARA_OA_002)
The purpose of the Trial is to measure the change in pain and function after subcutaneous injections of PPS compared with subcutaneous injections of placebo in participants with knee osteoarthritis pain.
This is a 2-stage, adaptive, randomised, double-blind, placebo-controlled, multicentre (US/AUS/UK/EU) study that will evaluate the dose and treatment effect of PPS in participants with pain associated with knee osteoarthritis.
The primary endpoint in the Trial will be change from baseline at Day 56 in WOMAC® pain with secondary outcomes to include change from baseline at multiple time points out to day 168 in WOMAC® Pain and Function, Patient Global Impression of Change (PGIC) and Quality of Life (QoL).
Market Potential in Osteoarthritis
Osteoarthritis (OA) is the most prevalent form of joint disease, affecting up to 16% of the population in the developed world, with more than 72 million people in the US, EU5, Canada and Australia suffering from osteoarthritis.2
OA has a significant impact on day-to-day functioning and, although the levels of pain and disability may fluctuate, it has no known cure or spontaneous remission and is associated with irreversible structural damage and progression over time. Presently there are no drugs approved that can prevent, stop, or even restrain progression of OA. Moreover, the available medications that claim to mitigate the pain of OA have numerous risk/benefit considerations.
The prevalence of OA is increasing in line with the aging population and increasing rates of obesity. By 2030 the number of people suffering from OA in the US alone is predicted to increase by 86% to 67 million.3 If we assume a similar increase across the other markets defined above, even allowing for lower rates of obesity in non-US markets, it is plausible that more than 120 million people will be suffering from osteoarthritis by 2030.
Zilosul® is a registered Trademark of Paradigm Biopharmaceuticals Ltd
To learn more please visit: www.paradigmbiopharma.com
