A new class of anti-inflammatory agent, the COX/LO inhibitor, had successful and safe results in two recent phase II clinical trials. The compound known as ML3000 is being developed as a treatment for osteoarthritis in the United States.
ML3000, an anti-inflammatory, works by inhibiting the enzymes cyclooxygenase (COX) and 5-lipoxygenase (LOL), hence the name COX/LO inhibitor. Several studies have demonstrated that the anti-inflammatory and pain-relieving abilities of the agent in osteoarthritis (OA) sufferers is comparable to conventional NSAIDs (Non-steroidal anti-inflammatory drugs) and Cox-2 inhibitors.
An additional benefit of this new type of drug is that the usual levels of gastrointestinal side-effects associated with traditional Cox-2 inhibitors were not experienced in the studies. The main side-effects noted with ML300 were diarrhea and abdominal pain.
According to a report in Business Wire, ML3000 is unique because it allows for a well-balanced inhibition of both key enzymes involved in the inflammatory process – Cox and LO. This is important, the report explains, since ML3000 inhibits both Cox-1 and Cox-2 non-selectively, yet is then able to accommodate the body’s physiologic reaction to Cox inhibition. This reaction is to shunt over to the LO pathway of the arachidonic acid cascade. ML3000 blocks the effects of this shunt by additionally blocking LO.
This shunt protection is a vital factor in the way that ML3000 works. LO stimulates the production of a substance called leukotriene, which is the cause of GI damage. When LO is inhibited, leukotriene production is also inhibited, resulting in a decreased risk of GI damage.
In the first study, 107 patients with OA received either ML300 at various doses or placebo for four weeks. Participants receiving ML3000 reported a decrease in the severity of their OA symptoms.
In a second study, 404 OA patients received either ML3000, diclofenac (a type of NSAID) or placebo for four weeks. The OA patients experienced an improvement in pain and mobility, compared to those who were given placebo. The scores were the same for the ML3000 and diclofenac group.
Merckle, a pharmaceutical company, discovered ML3000 and is partnering with Forest Laboratories for the licensing and development of the drug. A spokesman for Forest labs said, “New treatments to manage osteoarthritis are needed because there are many patients who are not adequately treated with the available current medications.” The new partnership will enable phase III testing to go ahead, which the company hopes “might well demonstrate that COX/LO inhibition will result in new pharmaceuticals better suited to the needs of patients than such drugs as the recently introduced COX-2 inhibitors.”
Osteoarthritis is a degenerative joint disease affecting more than 16 million Americans and is the most common form of arthritis.