Positive results from an in vivo study model using Incannex Healthcare’s (ASX: IHL) lead candidate IHL-675A have triggered the launch of a sixth clinical program investigating the benefits of the drug on the treatment of rheumatoid arthritis.
The study model assessed the anti-inflammatory capabilities of IHL-675A – which combines cannabidiol (CBD) and hydroxychloroquine (HCQ) – and found it to be more effective in treating rheumatoid arthritis than either CBD or HCQ alone.
HCQ is widely used for the treatment of rheumatoid arthritis in the form of hydroxychloroquine sulphate, marketed as Plaquenil.
A low dose of IHL-675A was found to be up to 3.52 times more effective at reducing arthritis across multiple assessments including clinical score, paw volume, pannus score, total histology score and serum cytokine levels as the standard dose of HCQ.
The study’s results demonstrate that IHL-675A has the potential to permit a tenfold reduction in HCQ dosage, without sacrificing efficacy, which according to Incannex could have implications for product safety and the potential to be a breakthrough in the treatment of rheumatoid arthritis.
Incannex has previously demonstrated the potent anti-inflammatory activity of IHL-675A in in vivo and in vitro studies, making it a strong candidate for the prevention and treatment of inflammatory lung conditions including sepsis-associated acute respiratory distress syndrome, chronic obstructive pulmonary disorder, asthma and bronchitis.
It has also more recently been shown to be effective in treating colitis, a form of inflammatory bowel disease.
In the study model, female Lewis rats received a dose of porcine type-II collagen with a Freund’s adjuvant booster via subcutaneous injection at the base of the tail to induce arthritis.
A booster shot was administered seven days after and on day 16, the rats were allocated into 10 groups of six including one sham group.
CBD, HCQ or the combination of both (IHL-675A) were injected intraperitoneally once per day from day 17 to day 30, for a total 14 days.
On day 30, blood was collected from all rats and analysed for levels of inflammatory cytokines known to be involved in the pathophysiology of rheumatoid arthritis, using commercially-available ELISA kits.
Both hind paws were harvested, weighed and formalin-fixed for histopathology, comprising evaluation of cartilage and bone destruction by pannus formation (an abnormal layer of fibrovascular or granulated tissue), and mononuclear cell infiltration in synovial joint tissues.
A total histology score – which is a sum of the pannus formation and mononuclear cell infiltration scores – was also calculated.
For all assessments, the score was sham subtracted and the reduction relative to the vehicle group was calculated.
Outperforming CBD and HCQ
IHL-675A was found to have outperformed equivalent doses of CBD and HCQ at reducing clinical score and paw volume at day 24 and day 30; pannus formation; serum cytokine levels; and total histology score in the rat model of arthritis.
The reduction in disease assessments by IHL-675A was up to 8.72 times that observed for HCQ alone at an equivalent dose and indicates that IHL-675A has a benefit in a rat model of arthritis greater than that of CBD or HCQ alone.
Incannex managing director Joel Latham pointed to a “potent benefit” of the CBD-HCQ combination in IHL-675A.
“HCQ is an established medication for rheumatoid arthritis and IHL-675A has now been demonstrated to outperform it at reducing disease severity in an animal model,” he said.
“The observation that IHL-675A was as effective or better than a standard HCQ dose even though it contains 90% less of the drug is an exciting result for [us] and indicates that IHL-675A has the potential to be a breakthrough in the treatment of rheumatoid arthritis in humans.”
Mr Latham said the company will be working with its scientific team and advisors to advance IHL-675A for use in patients with rheumatoid arthritis.
An autoimmune disorder, rheumatoid arthritis is a chronic inflammatory condition which occurs when the immune system mistakenly attacks the body’s tissues, damaging a variety of systems including skin, eyes, lungs, heart and blood vessels.
Unlike the wear-and-tear damage of osteoarthritis, rheumatoid arthritis affects the lining of the joints, causing a painful swelling which can eventually result in bone erosion and joint deformity.
Rheumatoid arthritis is believed to have a global addressable treatment market of around US$57 billion (A$73.76 billion) per annum.