Paradigm Biopharma’s knee osteoarthritis trial meets secondary endpoints, launches capital raise

Paradigm Biopharmaceuticals (ASX: PAR) has announced trial patients being treated with its injectable pentosan polysulfate sodium (iPPS) drug for osteoarthritis of the knee have confirmed improved knee function and pain reduction for six months.

The biotechnology company today confirmed its phase 2b clinical trial has successfully met its key secondary endpoints of improved knee function and pain reduction, as well as reporting a reduction in bone marrow lesion grade, volume and area.

This follows Paradigm’s announcement in December upon meeting the primary endpoints of the trial, confirming that iPPS was “safe and clinically effective”.

In addition, the company has the claimed a reduction of bone marrow lesions points to the potential of iPPS to slow the progression of the disease.

Phase 2b trial

The phase 2b clinical trial evaluated the effects iPPS had on 112 patients over a period of a little more than 12 months.

One of the secondary endpoints of the trial was measuring ‘activities of daily living’ (ADL), which is one of five subscales of the Knee Injury Osteoarthritis Outcome Score (KOOS). ADL includes 17 different physical functions such as ascending/descending, standing, going shopping and putting on socks, with patients scoring the degree of difficulty in achieving each task.

According to Paradigm, subjects treated with iPPS demonstrated a “statistically significant” greater improvement in ADL scores from baseline compared to patients treated with a placebo. In particular, iPPS-treated patients’ mean percentage change from baseline was 13% higher than placebo patients (39.6% versus 26.6%) from day 11 to day 165.

Another secondary endpoint of the trial was measuring the mean change in KOOS pain scores, with trial results demonstrating that the pain reducing effects of iPPS were durable over a six-month period.

Paradigm chief executive officer Paul Rennie said this KOOS pain reduction demonstrated “the potential of iPPS to be a long-lasting and efficacious pain treatment” in subjects with osteoarthritis.

In addition, the objective data endpoint measuring bone marrow lesion grade, volume and area by MRI at day 53 showed that the iPPS group had a “clinically meaningful reduction” compared to placebo.

According to Paradigm, data from iPPS-treated subjects showed that bone marrow lesion volume reduced by 34.2% compared to 3.6% in placebo subjects, while the area (size) reduced by 25.3% in iPPS patients compared to an 11.9% increase in the placebo group.

Possible disease regression

Mr Rennie said bone marrow lesions in osteoarthritis sufferers would traditionally remain the same size or get bigger over time.

“We see iPPS producing a net 65% reduction in BML volume in the NRS 4-6 strata, which is impressive, especially considering the MRI images were taken just two weeks after the last injection of iPPS, which is a very short time period after cessation of the drug,” he said.

“To have such a magnitude of difference on the total knee volume and area and statistically significant difference for the medical compartment of the knee is an amazing result and something that the medical, scientific and pharmaceutical fraternity will appreciate the importance of,” Mr Rennie added.

According to Paradigm, the effects on bone marrow lesions was “likely to translate to halting disease progression and promoting regression of disease and the facilitation of pain reduction and improvement in physical function”.

The company said the MRI data further validated the safety of using iPPS compared to anti-nerve growth factor agents like Tanezumab, which can result in adverse effects such as rapidly progressing osteoarthritis and osteonecrosis.

“Bone marrow lesions that persist and enlarge are strongly associated with cartilage loss and are a harbinger for total knee replacement, therefore the reduction in bone marrow lesion size and grade by iPPS therapy may stave-off the need for total knee replacement,” Paradigm stated.

Capital raise

Paradigm also today announced the launch of a $77.9 million capital raise to fund its osteoarthritis and mucopolysaccharidosis (MPS) programs through to the end of their clinical studies, new drug applications and possibly further intellectual property acquisitions.

The offer comprises a $51.6 million placement to professional, institutional and sophisticated investors across Australia, Asia and the United States including some existing shareholders, plus a $26.3 underwritten 1-for-8 accelerated non-renounceable entitlement offer to all eligible Australian and New Zealand registered shareholders.

Some of the proceeds are planned to be used to start an osteoarthritis phase 3 pivotal trial in the US, Europe and Australia.

The company also expects to use the funds to complete a phase 2/3 pivotal clinical trial in MPS, which is a rare genetic disorder that results in the body having insufficient enzymes needed to break down long chains of sugar molecules, leading to cell, tissue and organ damage.

The remaining balance of funds from the capital raise (about $38 million) will be used for new drug applications, working capital, offer costs, further pre-clinical studies and possible intellectual property acquisitions, Paradigm said.

Following the capital raising, the company said it expects to have a cash position of $82 million, which should put it in a strong negotiating position for commercial transactions.