Paradigm steps closer to Phase 3 trial for knee arthritis treatment after FDA feedback

Paradigm has received a positive response from US FDA for progression of its Phase 3 trial of injectable pentosan polysulfate sodium for knee osteoarthritis.

Paradigm Biopharmaceuticals (ASX:PAR) FDA provides progression of its Phase 3 trial of injectable pentosan polysulfate sodium for knee OA.

• Paradigm receives positive response from US FDA for progression of Phase 3 trial

• FDA confirmed its Phase 2 trial data supported safety and tolerability of twice weekly 2mg/kg dosage

• Once updated protocol is submitted to FDA, Paradigm anticipates 30-day review period before starting to enrol patients

Special Report: Late-stage drug development company Paradigm Biopharmaceuticals has a clear pathway from the FDA for progression of its Phase 3 trial of injectable pentosan polysulfate sodium (iPPS) for knee osteoarthritis (OA).

Paradigm Biopharmaceuticals (ASX:PAR) said it had received a detailed set of comments from the FDA following the Type D meeting response submitted in April 2024, which will progress its Phase 3 (PARA_OA_012) trial of iPPS for knee OA.

PAR said the regulatory body confirmed that its Phase 2 clinical data (PARA_005 and PARA_OA_008) supported the safety and tolerability of the twice-weekly 2 mg/kg dose, and that the clinical monitoring for adrenal effects would continue.

The company said the FDA has also provided guidance on the use of the selected dosing regimen of 2 mg/kg iPPS, administered twice weekly.

“This is a significant outcome for Paradigm… based on the clinical data generated to date, with a dosing regimen of 2 mg/kg iPPS administered twice weekly, positions the phase 3 clinical trial for success,” PAR said in an ASX announcement.

PAR said the FDA also provided guidance on amendments to the monitoring and mitigation plan, as well as statistical considerations.

The company will implement changes, supported by clinical and nonclinical data from PAR’s development programs, into the updated protocol under the open Investigational New Drug (IND) application with the FDA.

PAR is developing iPPS for the treatment of OA and mucopolysaccharidosis, where inflammation significantly contributes to the disease process.

Phase two 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.

Next steps for Phase 3 trial

Once the protocol is submitted, Paradigm expects a 30-day review period before proceeding with enrolment for the Phase 3 trial.

PAR said it had started to incorporate the FDA comments into its Phase 3 trial protocol and once completed, would submit the updated protocol under the open IND application.

The company expects to begin pre-screening and enrolment activities for PARA_OA_012 following the 30-day review period, with preparations already underway at trial sites in both the US and Australia.

‘Clearer, more defined path forward’

PAR managing director Paul Rennie said he understood many investors were eager to know the dosage to be used in the pivotal Phase 3 clinical trial.

“I am pleased to announce that the FDA has confirmed our clinical data supports the safety and tolerability of the twice-weekly administration of 2 mg/kg, the same dosing regimen we used in our phase 2 clinical studies,” he said.

“We are grateful to the US FDA for their valuable guidance on the Phase 3 protocol.”

Chief medical officer Dr Donna Skerrett said she believed the clarity provided by the FDA's response had brought PAR one step closer to entering the pivotal phase of the program.

“We now have a clearer, more defined path forward, allowing us to optimise the clinical protocol,” she said.

“We are incredibly proud of the collaborative efforts and hard work that have led us to this point, and we are excited to move forward with a protocol designed to maximise our chances of success.

“The alignment with the FDA’s guidance further strengthens our confidence as we progress towards a successful outcome and move closer to securing approval for iPPS.”

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.