Rheumatoid Arthritis (RA) is a chronic, progressive and currently incurable autoimmune disease that primarily affects the joints. It is characterized by synovial inflammation and gradual bone erosion over many years. Disease progression results in stiffness and pain, especially in the hands and feet, which hinders mobility. Without treatment, the disease leads to joint destruction and disability.
The chronic nature of the disease, which requires ongoing treatment, and the relatively high annual cost of therapy (ACoT) have made RA treatment a highly lucrative market. The RA therapeutic market has become very competitive due to the high number of new drug approvals. Competition is fierce, particularly among TNF-? inhibitors, which dominate the treatment market for RA patients who are refractory to traditional disease-modifying anti-rheumatic drugs (DMARD).
Despite this, 30% of RA patients fail to attain a clinical response when treated with TNF-? inhibitors. However, other targeted programs, as well as newly marketed small-molecule DMARDs such as the Janus kinase (JAK) inhibitor Xeljanz (tofacitinib), have the potential to replace ineffective TNF-? inhibitors. Recently published study results of Xeljanz have shown a significant reduction in the risk of developing cardiac diseases such as heart attack and stroke in patients with RA.
Despite the superior efficacy of recently marketed therapies over traditional DMARD therapies, there is a need to improve safety in the therapeutic landscape. Elevated rates of infection are a frequent consequence of the immunosuppression involved in treatments, but this is required to suppress the autoimmune responses responsible for the symptoms of the condition.
As a result, these biological therapies are not recommended to patients who are susceptible to infection. In addition, there is a need to create biologics with more convenient and less invasive drug-delivery methods, as all existing therapies are administered subcutaneously or intravenously.
These routes of administration are frequently associated with pain, rash, and allergic reactions at the injection or infusion site and, in the case of infusion, flu-like illness, fever, chills, nausea, and headache. Therefore convenient and safe administration without significant compromise of therapy efficacy remains an unmet need.
Although the recently approved drug Xeljanz is an orally administered small-molecule drug, indicated as a second-line treatment for RA patients who have not shown an adequate response to methotrexate, and as a third-line therapy for patients who have not responded sufficiently to biologics, it carries a black-box warning in the US due to the safety issues of serious infections and malignancy.