The primary outcome of the trial is to evaluate the effects of injectable pentosan polysulfate sodium (iPPS) on knee pain in subjects with knee OA and subchondral bone marrow edema lesions (BMELs).
This is assessed by the KOOS pain subscale using a numeric rating scale (NRS), a NRS 4-6 is moderate pain and an NRS 7-8 is high pain.
46.2% of subjects receiving iPPS showed a greater than 50% reduction in pain from baseline compared to 22.5% of subjects receiving placebo under KOOS pain subscale.
Investors responded positively, with Paradigm up as much as 63% to an intra-day high of $2.15, which is also a new 12-month high.
The biotech’s objective is to advance the clinical development plan for iPPS as an effective treatment for OA which will include filing a new drug application (NDA) with the USA Food and Drug Administration (FDA) for a phase III clinical trial next year.
Paradigm’s CEO Paul Rennie said the Paradigm clinical and regulatory team, along with all the clinical trial recruitment and treatment centres, had done an extraordinary job concluding the trial in just over 12 months.
Results for phase II include only top line data and analysis of the secondary endpoints is ongoing.
However, initial comparisons with placebo, clinical and statistical differences were achieved in the NRS pain score (day 39 to 53), patient global impression of change (PGIC) and proportions of subjects with 50% reductions in timepoints other than day 53.
Full reporting on secondary endpoints will be provided in the first quarter of calendar year 2019, likely in conjunction with a peer-reviewed publication or presentation at a global orthopaedic conference.
The key outcome from the phase II trial was that clinically meaningful and statistically significant results between iPPS and placebo were demonstrated across the total subject population.
Clinically meaningful and highly statistically significant results were also demonstrated in the NRS pain levels 4-6 stratum.
1. Khanaoure A, Chuki P & De Sousa A (2014); 2. Ashurn T & Thor K (2004)
“High probability the drug will pass a phase III clinical trial”
Rennie said: “To achieve clinically meaningful and statistically significant results between iPPS and placebo in the total population and highly clinically meaningful and highly statistically significant results in the NRS = 4-6 strata is truly an outstandingly positive trial outcome.
“If you have clinical significance and statistical significance you have a high probability the drug will pass a phase III clinical trial and once registered a drug that can penetrate the market.
“We are further impressed with the results given the widespread difficulty ASX-listed biotechnology companies have had in achieving positive phase IIb trial results over the last few years.”
READ: Paradigm Biopharmaceuticals gains on market with upcoming clinical trial read-out, wider treatment potential
Paradigm believes iPPS has the potential to receive fast-track designation from the FDA which is greatly concerned about the opioid epidemic.
The company notes a statement from the FDA commissioner Scott Gottlieb that one of the FDA’s goals is to “identify and encourage the development of new treatment options that don’t have the addictive features of opioids”.
Fast-track is a process designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need.
Paradigm’s iPPS is neither an opioid nor a steroid, and most importantly is non-addictive, creating the potential to positively impact the opioid epidemic and treat OA pain.
“Significant boost to partnering prospects”
Paradigm chairman Graeme Kaufman said: “The combined data from this trial support the high number of patients treated by their doctors via the TGA SAS.
“[The data] give us confidence that iPPS has the potential to be a safe, effective, long-lasting, non-opioid-based treatment for knee OA.
“Going forward we will be releasing additional SAS data on knee OA but also other joints which will broaden the applicability of the potential of iPPS as an OA pain reduction treatment.
“Today’s ground-breaking data also greatly strengthens the iPPS/OA licensing package and provides a significant boost to partnering prospects.”
READ: Paradigm Biopharmaceuticals ‘next Australian blockbuster biotech’, according to Fiftyone Capital
A recent report from Fiftyone Capital said Paradigm was shaping up to be the next major Australian biotech success story, predicting a less than 1% risk of failure for completed OA phase-2b clinical trial.
Provided Paradigm successfully signs licencing deals or commercialises all three of its current indications, the report anticipates a plus-$30 share price and market capitalisation around $5 billion.
The report notes the potential to identify other indications that have inflammatory issues as a symptom that could also be treated using iPPS.
Paradigm's share price over 13 months
READ: Paradigm Biopharmaceuticals’ positive trial results potentially transformational, says Morgans research
Speaking at the company’s annual general meeting in August, Kaufman said there was a global trend for safe and effective non-opioid, non-steroid pain relief for chronic disease such as OA.
Kaufman said: “[This] presents a huge market opportunity for Paradigm’s iPPS.
“Like our OA program, [the Ross River virus program] is also a very exciting commercial opportunity.
“There are currently no registered therapeutics to treat the 10,000 cases of Ross River infections in Australia each year, nor the closely-related alpha virus Chikungunya.
"Chikungunya virus is endemic in many countries and there are millions of cases diagnosed each year again with no registered therapeutics to treat this debilitating disease.”
Paradigm recently executed an agreement with a US-based medical school for use of its iPPS in the treatment of mucopolysaccharidoses (MPS).
The exclusive in-licence agreement covers the use of iPPS for MPS, a rare inherited disease which causes debilitating joint pain and dysfunction and a key unmet medical need in this class of inherited disease is the lack of treatment.
The company has also entered into a heads of agreement (HoA) regarding a strategic partnership with the New York-based Pro Players’ Elite Network (PPEN) to recruit and treat US-based sportspeople.
The partnership will be under a proposed FDA expanded access program commonly referred to as the ‘compassionate use’ program.
Paradigm views the partnership as an opportunity to not only treat people in need but to gain substantial exposure and promotion of the company and its treatment in the United States.
The US market is a key focus for Paradim given the significant number of OA sufferers – amounting to around 31 million – and in particular the large number of sportspeople and NFL players suffering from OA who are being prescribed opioids for chronic pain management.
Paradigm chief executive officer Paul Rennie said of HoA with PPEN: “Given the success Paradigm has had treating current and retired sportspeople, the company has been actively exploring ways to enter the US.
“Working with past elite sporting organisations such as PPEN allows us to gain access to a range of sportspeople in the US who would be ideal treatment candidates for iPPS.
“Paradigm will be able to work with and leverage the various sporting medical relationships that PPEN has in the US, which can potentially expedite our future US programs.”
The company said it was confident the Therapeutic Goods Administration (TGA) special access scheme results, averaging 51.5% or greater pain reduction for knee pain in 125 patients, will be replicable in the US.
Paradigm has executed a 20-year exclusive supply agreement with bene PharmaChem GmbH & Co, the original developer and only FDA-approved manufacturer of PPS.
The agreement grants exclusive supply of only FDA-approved PPS for all orthopaedic including alphavirus respiratory and cardiovascular indications.
Under the agreement Paradigm will pay PharmaChem a single digit royalty on commercial sales.
Paradigm has also patented its specific indications to a minimum of 2030, with established regulatory exclusivity and trademarks.
Patent applications have been made for OA and concurrent BMEL, Ross River virus and Chikungunya virus.
iPPS is not currently registered in Australia but is registered in four of the seven major global pharmaceutical markets.
In European markets, iPPS is registered as an antithrombotic agent.
iPPS for human use is not available for sale in Australia and is only available by inclusion into a Paradigm-sponsored clinical trial or via a treating physician applying for its use in patients via the Therapeutic Goods Administration’s SAS category B.