Inflammatory bowel disease (IBD)

IBD is a group of inflammatory conditions of the gastrointestinal tract, comprised mainly of ulcerative colitis (UC) and Crohn’s disease.

UC causes diffuse inflammation and ulcers in the innermost lining of the large intestine (colon, rectum and terminal ileum). Crohn’s disease is characterized by distinct patches of inflammation, which may penetrate the entire thickness of the intestinal wall. Crohn’s disease is found anywhere in the intestinal tract (from mouth to anus)

IBD can occur in people of all ages, but patients are more frequently diagnosed before the age of 30. Both conditions inflame the lining of the intestine, resulting in symptoms including:

  1. Diarrhea
  2. Fever
  3. Abdominal cramps
  4. Pain
  5. Rectal bleeding or bloody stools

Current treatment options

IBD patients may progress through at least three lines of treatment (the so-called “step-up” therapy approach) before surgical intervention. Current treatment options include first-line treatments (mesalamines), second-line treatment (corticosteroids and immunomodulators) and third-line treatment (anti -TNF-agents and integrin receptor antagonists).

Mesalamines are minimally absorbed into the systemic circulation, reducing the risk of systemic side effects. However, only about one third of UC patients achieve remission, with efficacy in Crohn’s disease generally considered to be even poorer. Common side effects include headache, nausea and diarrhea.

The majority of patients will require a second-line treatment (corticosteroids and immunomodulatators). It is well described in literature that steroids can cause significant side effects when used chronically. Immunomodulators, however, are potent agents, but are accompanied by immunosuppressive side effects, including serious infections and malignancies.

3rd line treatment before surgical intervention includes anti-TNF agents and integrin receptor antagonists. They are currently used primarily in patients who have failed conventional therapies. The major concerns around these agents is that they can lead to auto-immune disease, e.g. lupus-like syndrome. In addition, there is the risk of serious infections (including re-activation of tuberculosis), malignancies and congestive heart failure (worsening or new onset). Due to how these drugs are administrated, there is also a risk of infusion site or injection site reactions.

Development of more effective, safer and less invasive treatments would help to address the clinical need and reduce the side effects of the drugs. An oral treatment, such as AKB-4924 now GB004, could offer a novel approach which targets both resolution of inflammation and mucosal healing, while potentially avoiding the risk of immunosuppressive adverse events.