Pancreatic cancer, unless controlled at its earliest stages, tends to spread to local tissues and to distant organs. Although surgery can be curative if pancreatic cancer is diagnosed at its very earliest stages, once the cancer has spread to distant organs, the current treatment has some, although limited, efficacy. New treatments are clearly needed. RAGE has been implicated in the growth and spread of pancreatic cancer and its resistance to radiation and chemotherapy.
The spread (metastasis) of cancer to the brain is a common occurrence in patients with advanced lung cancer and breast cancer, as well as many other cancers. Brain metastases can be resistant to the effect of radiation therapy and pre-clinical data suggests that RAGE inhibition may overcome this resistance.
Glioblastoma is a highly malignant brain tumor for which current therapeutic options provide only a modest improvement in outlook. New treatments of glioblastoma are urgently needed. RAGE may play a role in the growth and invasiveness of glioblastoma and its resistance to current treatments.
Although great strides have been made with current treatments of locally advanced breast cancer, women remain at risk for cancer recurrence and metastasis. The risk of recurrence and metastasis is clearly reduced by chemotherapy and immunotherapy, but chemotherapy commonly impairs cognitive function. Azeliragon, in laboratory studies, prevented cognitive decline after chemotherapy as well as inhibited metastasis of breast cancer.In pre-clinical models of of triple-negative breast cancer, an aggressive type of breast cancer, azeliragon prevented the development of metastases.
Antibiotics effectively treat pneumonia. However, when pneumonia is advanced or severe, especially in the elderly or those with chronic illnesses, local and systemic inflammatory responses, driven by RAGE activation, can trigger lung and kidney failure. This can lead to prolonged hospitalization and increased mortality. The ongoing azeliragon phase 3 trial endpoints include reduction of the risks of lung and kidney failure, as well as the risk of extended hospitalization and mortality.
Asthma is common. According to current Centers for Disease Control, asthma has a prevalence of over 7% in the U.S., with over 20 million Americans over 18 years suffering from asthma. For many asthmatics, symptoms of asthma are inadequately controlled by existing medications. In pre-clinical models, azeliragon has shown promising activity as a treatment of asthma.
RAGE is the major driver of lung inflammation and disease progression in COPD. With moderate to severe COPD, exacerbations requiring hospitalization and re-hospitalization are common (>700,000 per year in US), with each exacerbation associated with more loss of lung function, and increased risk of death. Clinical trials of azeliragon in moderate to severe COPD, will seek to reduce the risk of these disabling and life-threatening exacerbations.
