Cancel
Alphavirus-induced
ARTHRITIS
The biological processes associated with alphavirus-induced arthritis include inflammation, tissue damage and/or adverse tissue remodelling.
Ross River virus (RRV) and Chikungunya virus (CHIKV) are two closely related arthritogenic alphaviruses transmitted by mosquito bites. Infection typically results in acute symptoms of fever, malaise and pain in the joints and muscles.
RRV outbreaks are mostly restricted to Australia, while CHIKV circulates predominantly in tropical and subtropical regions, causing large scale epidemics of severe musculoskeletal disease.
Musculoskeletal manifestations of disease have been shown to affect 42.5% of those infected with CHIKV.
Research indicates that analgesic and non-steroidal anti-inflammatory drugs may be ineffective in the management of arthralgia (painful joints), and many patients are left incapacitated with symptoms which may persist for many months or years.
Clinical development of pentosan polysulfate sodium (PPS) as a therapy for the joint symptoms of RRV and CHIKV follows compelling preclinical evidence in alphavirus models.
Results from studies conducted to date provide both a clinical and scientific basis for the design of a larger clinical trial in CHIKV-induced arthralgia.
Alphavirus-induced
ARTHRITIS
The biological processes associated with alphavirus-induced arthritis include inflammation, tissue damage and/or adverse tissue remodelling.
Ross River virus (RRV) and Chikungunya virus (CHIKV) are two closely related arthritogenic alphaviruses transmitted by mosquito bites. Infection typically results in acute symptoms of fever, malaise and pain in the joints and muscles.
RRV outbreaks are mostly restricted to Australia, while CHIKV circulates predominantly in tropical and subtropical regions, causing large scale epidemics of severe musculoskeletal disease.
Musculoskeletal manifestations of disease have been shown to affect 42.5% of those infected with CHIKV.
Research indicates that analgesic and non-steroidal anti-inflammatory drugs may be ineffective in the management of arthralgia (painful joints), and many patients are left incapacitated with symptoms which may persist for many months or years.
Clinical development of pentosan polysulfate sodium (PPS) as a therapy for the joint symptoms of RRV and CHIKV follows compelling preclinical evidence in alphavirus models.
Results from studies conducted to date provide both a clinical and scientific basis for the design of a larger clinical trial in CHIKV-induced arthralgia.
Key CHIKV Figures
10 B+
≥95%
arthralgia
(at 12 months)
≥ 43%
Key RRV Figures
5000
≥95%
arthralgia
(at 3 months)
11%
Key CHIKV Figures
10 B+
≥95 %
arthralgia
(at 12 months)
≥43 %
Key RRV Figures
5000
≥95 %
arthralgia
(at 3 months)
11%
Mechanism of Action
Paradigm’s rationale for the use of PPS to target viral arthritis is based on the multiple mechanisms of action of PPS involving targeting inflammation, pain and joint degradation, which are attributed to the many molecular species of PPS consisting of numerous moieties.
PPS treatment was shown to significantly alleviate severity of RRV and CHIKV, by demonstrating a:
- Significant reduction in the inflammatory response (quantified by cytokine profiles)
- Significant reduction in the loss of articular cartilage
Inflammation
Cartilage Loss
Development milestones
In September 2016, Paradigm Biopharmaceuticals Ltd announced a collaborative partnership with the Institute for Glycomics at Griffith University, whereby Paradigm was granted exclusive worldwide rights to commercialise the use of PPS to treat alphavirus-induced arthritis and joint pain. Paradigm Biopharmaceuticals Ltd has since been granted the relevant global patents.
Paradigm has conducted a successful Phase 2a randomised, double-blinded placebo-controlled pilot clinical trial in participants with persistent RRV-induced arthralgia treated with injectable PPS.
A preclinical study has demonstrated successful PPS treatment of arthralgia in CHIKV-infected mice.
For more information and updates, please see our ASX announcements.
CHIKV
RRV
