Melanocortin derived therapy applied in the clinic- Current status and potential for the future

ACHTAR gel (repository corticotropin injection), Mallinckrodt Pharmaceuticals is a marked approved compound for injection. The compound has been on the market for many years. The active ingredient(s) in the compound is extracted from pituitary glands and was originally thought to induce its pharmacological effects though release of glucocorticoids (GCs) from the adrenal glands through stimulation of the MC2r receptor. The active ingredient in  ACHTAR Gel is ACTH = AdrenoCorticoTropic Hormone and the compounds ability to stimulate GCs has for years been the explanation to why ACHTAR gel and other (synthetic) ACTH containing compounds induced anti-inflammation. However, ACTH is a full agonist on all the five Melanocortin receptors and a number of recent studies has shown that ACTH induce anti-inflammatory and pro-resolving effects independent of GCs. Actually, it has been reported that ACTH derived therapy is active in sub-population of patients with symptoms resistant to high dose GC treatment. Lately Mallinckrodt Therapeutics has reported positive treatment effect in difficult the treat Rheumatoid Arthritis patients resistant to GC treatment.

The reposition of ACHTAR gel in difficult to treat cases, within rheumatoid diseases, Multiple Sclerosis, Nephrotic syndrome, and other inflammatory and auto-immune diseases was made by the California based specialized Pharma company Questcor. Based on an annual sale of ACHTAR above 1 BUS$ Mallinckrodt Pharmaceuticals acquired Questcor in deal of a total value around 5.5 BUS$ and has continued the development, promotion and sale of ACHTAR gel with a continued annual revenue above 1 BUS$.

Due to the side-effect profile of ACHTAR gel the use in the clinic is limited to difficult to treat cases where other treatment strategies have shown insufficient. However, the fact that the compound is active in patients resistant to GC treatment highlight the potential of new treatments targeting the melanocortin receptors (MCrs) for the treatment of inflammatory and auto-immune diseases, ie a compound that stimulated relevant subtypes of MCrs, ie the MCr1 and MC3 within the immune system, but not the MCr2 on the adrenal glands, could induce a break though in melanocortin-receptor derived therapy in inflammatory and auto-immune diseases.

SynAct Pharma´s lead compound is a biased MC1r and MCr3 agonist that induce anti-inflammatory and pro-resolving effects in diseases model to the same level as classical peptide MCr agonists as well as ACTH. The compound is currently in Clinical Phase 2a development with the aim to generate not only additional safety data to the ones collected in the recently completed Phase 1 development , but also to shown effects of key read outs for treatment effects- Currently a study in patients with active Rheumatoid Arthritis is ongoing where the compound is given as add on to Methotrexate in previous Methotrexate naive patients.