Paradigm Biopharmaceuticals has suffered a setback after an independent monitoring board found that its Phase 3 knee osteoarthritis trial failed to meet the efficacy threshold required to continue.
The Melbourne company's shares remain suspended, and its funding arrangements are under review.
The Data Safety Monitoring Board confirmed that the interim efficacy result for the PARA_OA_012 trial fell below the threshold set in the study design. The trial is testing injectable pentosan polysulfate sodium, known as iPPS or Zilosul. As a result, the trial met its predefined futility criterion.
The interim analysis occurred after about half of participants reached the Day 112 primary efficacy endpoint. The observed treatment effect fell short of the minimum required for continuation, which suggests the study is unlikely to meet its primary endpoint at the final analysis. The board reviewed unblinded efficacy and safety data.
The company said operational problems in running the trial led to a significant amount of missing data, which had affected the interim results.
Executive Chairman Paul Rennie said the company shared investors' disappointment. "The Board and the entire Paradigm team are deeply disappointed by this outcome. We recognise the disappointment it brings to our shareholders and everyone who has supported the program," he said.
"An initial review, by Paradigm's unblinded clinical staff, identified missing data. Under the statistical analysis plan, missing data is imputed and this imputation impacted the efficacy outcome. This is very disappointing given our broad and positive experience with iPPS in treating osteoarthritis. We remain optimistic in the therapeutic potential of PPS in treating osteoarthritis."
"PARA_OA_012 treated 538 participants. We are continuing to review the available data to gain further information and better understand the impact of the operational challenges and missing data."
Paradigm said it would work with the monitoring board, its clinical partners and investigators to decide what study activities and database processes remain. Once the database and unblinding processes are complete, the company will conduct a detailed review of the Phase 3 data. That review will cover pain, function, safety and other predefined endpoints, and it will guide the program's next steps.
The Zilosul osteoarthritis program has Fast Track designation from the US Food and Drug Administration. However, the company said it would reassess the timing, scope and objectives of future regulatory engagement after the data review. Any future clinical or regulatory strategy will depend on the Phase 3 dataset and, where appropriate, on discussions with regulators.
"Paradigm retains a substantial intellectual property portfolio. We are assessing the best path forward for the Company and its assets, and the Board will provide further updates as information becomes available," Mr Rennie said.
The board is examining the potential costs of winding down the trial, its remaining contractual commitments, its future funding needs and the company's rights and obligations under its existing funding arrangements.
Paradigm said it is in talks with Obsidian Global GP, LLC, which provides its secured convertible note facility, about what the trial result means under that facility. The company said it could not be certain how those discussions would end or when the outcome would be known. It acknowledged material uncertainty about the financial and operational consequences of the result, and said it cannot yet quantify the full impact.
