Paradigm clear for phase 3 following US FDA review

US FDA successfully concludes 30-day review of Paradigm Biopharmaceuticals phase III trial protocol
Pivotal trial of repurposed pentosan polysulfate sodium (Zilosul) to treat knee osteoarthritis due to start in Q1 CY25
Paradigm to progress talks with potential partners looking to support and/or co-fund trial and future commercialisation efforts

Special Report: The US FDA has successfully concluded a 30-day review period for Paradigm Biopharmaceuticals’ phase III pivotal clinical trial protocol of repurposed pentosan polysulfate sodium (Zilosul) to treat knee osteoarthritis (OA), clearing the way for a start date in Q1 CY25.

Paradigm Biopharmaceuticals (ASX:PAR) said no substantive questions or concerns were raised by the FDA and the company could proceed with the pivotal clinical trial PARA_OA_012, using the 2mg/kg twice-weekly dosing regimen of injectable (subcutaneous) pentosan polysulfate sodium (iPPS).

The 30-calendar day review period officially started on October 28 and concluded on November 27 2024 (US time).

Paradigm said preparations for PARA_OA_012 were well advanced, and the company was on track to start patient enrolment in Q1 CY25, with up to an initial 10 clinical sites in Australia, with sites in the US forecast to follow.

The phase III trial will enrol ~466 participants in a 1:1 randomisation design, with an interim analysis to assess potential early efficacy planned when 50% of subjects reach the Day 112 follow-up.

The primary endpoint of the pivotal phase III clinical trial is a change from baseline in pain. Key secondary endpoints include pain and functional assessments at multiple timepoints up to day 404, the Patient Global Impression of Change (PGIC), and structural changes as measured by MRI and X-ray.

The FDA’s feedback has been fully integrated into the pivotal phase III clinical trial design, clinical endpoints and statistical methodology, with structural changes now upgraded to secondary endpoints to enhance their importance in regulatory submissions and potential label claims.

Major milestone for Paradigm

The FDA green light for the phase III clinical trial represents a major milestone for Paradigm as it has progressed its clinical program.

The company said it could actively engage with key potential partners looking to support and/or co-fund the trial and future commercialisation efforts.

The FDA has the authority to engage with clinical trial sponsors throughout the conduct of a trial, ensuring compliance with regulatory standards and addressing potential concerns.

Phase II clinical trial data demonstrated a single six-week course of subcutaneous iPPS can provide 12-month pain relief and improved function in knee OA sufferers.

Data also showed improvement in cartilage volume and thickness at six months following treatment compared to placebo.

Paradigm said it was now focused on start-up and other preparatory activities to ensure timely initiation of patient enrolment.

‘Now a phase III company’

Managing director Paul Rennie said staff and consultants had worked hard with multiple submissions to the FDA to achieve approval for the phase III trial.

“Today I am pleased to report that Paradigm is now a phase III company,” he said.

“We are confident that, based on the clinical and other data generated to date and the enhancements to our trial design, informed by FDA guidance and commercial input, Zilosul is positioned as a leading therapeutic candidate for the large poorly met need of pain associated with knee osteoarthritis.

“I am excited by the various strategic options available to the company now we have progressed through this critical milestone.”

Paradigm also expects a response to its determination application recently submitted to the local Therapeutic Goods Administration by the end of December.

Approval would pave the way for a further submission to have Zilosul approved as a local knee osteoarthritis treatment ahead of formal approval.

This article was developed in collaboration with Paradigm Biopharmaceuticals, a Stockhead advertiser at the time of publishing.

This article does not constitute financial product advice. You should consider obtaining independent advice before making any financial decisions.