Paradigm Biopharmaceuticals Ltd (ASX:PAR) has cleared a regulatory obstacle by receiving Investigational New Drug (IND) application approval from the US Food and Drug Administration (FDA) for a phase 3 clinical trial investigating its proprietary drug Zilosul® – formulated from Pentosan Polysulphate Sodium (PPS) – for the treatment of pain associated with knee osteoarthritis.
Paradigm received Australian ethics approval for the trial on September 24, 2021. This clinical trial is supported by 26 non-clinical studies conducted by Paradigm, including studies that inform of the tolerance profile of PPS, its pharmacokinetics (absorption, distribution, metabolism, and excretion) profile and information that will be needed to identify the minimal effective dose through an initial dose-finding stage.
US FDA clearance for the trial saw shares increase as much as 30.6% within the first hour of ASX trading to A$2.69 while the company's market cap before opening was approximately A$468.1 million.
“Major milestone”
“The opening of the trial in the USA – the largest global pharmaceutical market, is a major milestone for the company," Paradigm CEO and interim chair Paul Rennie said.
"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.”
Roughly 65 suitable sites for the trial have been identified throughout Australia and the US, with patient screening in both countries expected to begin during this final quarter of 2021. The first four of eight sites have been initiated, with the remaining sites expected to be initiated before the end of the year.
In addition to US and Australian approval, Paradigm has the right to begin clinical trials in EU member countries. Paradigm believes these regulatory successes offer a “clear, harmonised path” to global approval of Zilosul®.
Ten additional sites in the UK and EU have been identified for trial and are expected to be initiated in the first half of 2022. Further updates will be provided once first patient milestones are achieved and will include a detailed overview of the clinical trial design and proposed timelines.
About the trial (PARA_OA_002)
The trial is designed to measure the change in pain and function after subcutaneous (beneath the skin) injections of PPS compared with 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).
The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) is a widely used, proprietary set of standardised questionnaires used by health professionals to evaluate the condition of patients with osteoarthritis of the knee and hip, including pain, stiffness, and physical functioning of the joints.
Observational follow-up
The PARA_OA_006 observational study has been designed to follow up the PARA_OA_002 trial and will evaluate the duration of treatment effect and safety up to 60 weeks following first injection with PPS in the trial. All participants who complete the trial will be invited to participate in the follow-up study.
Paradigm's previous phase 2b study completed in Australia followed patients out to day 165, so this follow-up study will provide important additional data on the duration of effect of PPS on patients over 12 months post treatment.
The data collected in this follow-up is expected to be highly valuable for the Zilosul® label and reimbursement discussions once registration can be achieved.
Market potential
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, EU, Canada and Australia suffering from osteoarthritis.
OA 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 and market research indicates that only 19% of knee OA patients are satisfied with currently available treatments.
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 alone is predicted to increase by 86% to 67 million. If a similar increase across the other markets is assumed, 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.
About the company
Paradigm Biopharmaceuticals is a late-stage drug development company with a mission to develop and commercialise pentosan polysulfate sodium (PPS) for the treatment of pain associated with musculoskeletal disorders driven by injury, inflammation, ageing, degenerative disease, infection or genetic predisposition.
Paradigm is also investigating proof-of-concept for the use of PPS in respiratory and heart failure indications.