The company presented at the 39th annual JP Morgan Healthcare Conference this week, outlining a roadmap that will take the business through to the middle of 2024.
It is confident it will make an Investigational New Drug (IND) submission with the US Food and Drug Administration by the end of this quarter, following positive feedback from its Type-C meeting with the FDA in December that gave the green light to the next phase.
In an interview with Proactive, Joughin said 2021 would see the beginning of the Phase 3 trial of Zilosul®, following a year of positive progress in 2020.
“We are confident we will commence the first of two pivotal studies, dosing the first US patient, by June,” she said.
Prep work all done
Paradigm spent a fair chunk of 2020 de-risking Zilosul® by seeking as much feedback from international regulatory bodies as possible.
It will use the same clinical trial protocol in the US, Europe and Australia, potentially enabling registrations in multiple jurisdictions, saving time and money.
“The feedback we gathered not just from the FDA, but also from several meetings with European regulators, means we have a globally harmonised protocol for Zilosul®,” Joughin said.
Minimum effective dose
Joughin said the regulatory bodies had asked Paradigm to investigate the lowest possible dosage of Zilosul® it could give to patients without compromising on efficacy, and this would be a focus of the Phase 3 trial.
Paradigm already has a wealth of Phase 2b data that confirms the effectiveness of Zilosul®, which is the company’s name for injected pentosan polysulphate sodium, a drug with a long history of use and a well-established safety profile.
Zilosul® has been shown to decrease pain, increase function and reduce the volume of bone marrow edema-like lesions in osteoarthritis patients’ knees.
“A focus of the Phase 3 trials will be to find out how little of it we can give to a patient and for it to remain effective,” Joughin said.
A key focus of the company’s presentation at the JP Morgan conference was to outline the interest in finding effective treatments for osteoarthritis.
Some of the biggest names in pharma, such as Pfizer, Sanofi, Mitsubishi Tanabe, MundiPharma and Galápagos, have made big-money plays for osteoarthritis treatments.
But Joughin says Paradim’s Zilosul® had an advantage over many of the drugs being investigated by big pharma – its multiple modes of action.
“There is a huge unmet need, with some 72 million people with osteoarthritis in the US, Canada, Australia and the top five European countries alone,” she said.
“And that is only people who have been clinically diagnosed, the number could be much higher.
“Many people are unsatisfied with the current available treatments. As the disease progresses, opioids are really the only thing on offer, and many young people suffering from the disease don’t want replacements.
“The pie is enormous, but many of the treatments being investigated are looking at only a single mode of action – perhaps they’re looking only at the inflammation aspect of osteoarthritis, or the pain aspect, or the cartilage loss aspect.
“Zilosul® tackles these three and also improves blood flow through self-adhesion molecules that target capitally endothelial cells that display anti-thrombotic effects.”
There are a whopping 81 per cent of osteoarthritis patients dissatisfied with current treatments, and Paradigm is targeting 10 per cent of that market, with Zilosul’s indicative price of US$2,500 per year.
The first trial readout for the Phase 3 trial is due to take place in quarter one of 2023, followed by a final readout in quarter three of 2023.
The company has a market cap of approximately $544.3 million and shares in the last 12 months have traded in the range of $1.08 to $4.50.
- Daniel Paproth