Lodotra^™ – Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic, progressive and disabling autoimmune disorder in which the immune system attacks the joints and other tissues of the body, causing tissue damage including erosion and destruction of the joint surface, as well as inflammation and joint pain. The symptoms of RA include progressive immobility and pain, especially in the morning, with long-term sufferers experiencing continual joint destruction for the remainder of their life. Morning stiffness of the joints is a hallmark of RA. Morning stiffness, with a duration of at least 1 hour, has been adopted as a diagnostic criterion for the definition of RA by the American College of Rheumatology (ACR). Inflammation, soft tissue swelling, and the involvement of multiple joints (in particular the small joints in the hands and feet) are also common signs and symptoms that distinguish rheumatoid and other inflammatory arthritis from non-inflammatory arthritis such as osteoarthritis.

The exact cause of RA is not known, but is believed to be a combination of genetic pre-disposition and environmental triggers such as allergens, infection and smoking. The identity of the antigen that initiates the RA inflammatory cascade is not known. Once the inflammatory cascade has been triggered, various immune components (e.g., IgG and IgM produced by B-cells) are deposited in the tissue, which leads to the activation of other arms of the immune system (e.g., cytotoxic T-cells, helper T-cells, macrophages and dendritic cells). Early mediators of inflammation include pro-inflammatory cytokines such as IL-1, IL-6, IL-8, IL-15 and TNF-α. The inflammation, in turn, leads to tissue damage and destruction, including cartilage loss and bone erosion. It is well recognized that increased levels of these pro-inflammatory cytokines during night-time hours are the primary cause of morning inflammation. This leads to sufferers becoming increasingly immobile, especially in the morning. Morning stiffness severely restricts sufferers from performing daily functional tasks such as washing, dressing and feeding themselves in the morning. Studies have shown that, even with treatment, 50 % of sufferers are unable to work due to their RA within 10 years of RA diagnosis, with most stopping work within the first 12 months after diagnosis, placing a significant burden on family carers, social services and the economy. RA-associated diseases include cardiovascular disease, osteoporosis, depression and sleep disturbances, some of which contribute to shortened life expectancy for RA patients.

Onset of RA is uncommon under the age of 15 and from then on the incidence increases with age with 55-60 years being the most common period of onset. RA is present in all ethnic groups, although is more prevalent in Anglo-Saxon and Native American Indian populations and less prevalent in the Mediterranean population. Overall, the prevalence of RA and RA-related diseases exceeds 1 % in the EU and US with women three-to-five times more likely to be affected than men. It is four times more common in smokers than in non-smokers. Also unknown environmental factors (e.g., viral infections) are thought to play a role.

Market size The pharmaceutical market for RA in the seven major pharmaceutical markets (the US, Japan, France, Germany, Spain, Italy and the UK) is estimated to be approximately US$ 6bn and has grown by 19 % per year from 2003 to 2006. The management believe that a substantial proportion of that market is currently held by standard prednisone. In a phase 3 clinical trial, Nitec has demonstrated superiority of Lodotra^™ over standard prednisone, namely in the reduction of morning stiffness and IL-6 levels. Nitec’s management therefore believes that Lodotra^™ will become the treatment of choice in RA.