Familial Adenomatous Polyposis (FAP) results from a germ line mutation in the Adenomatous Polyposis Coli (APC) gene. FAP is an autosomal dominantly inherited disorder, which is characterized by the formation of numerous colorectal adenomatous polyps and leads to the cancer of the large intestine (colon) and rectum. The mutation in the APC affects the ability of the cell to maintain normal growth and function. Cell overgrowth resulting from mutations causes complications in the form of colon and rectum cancer.
The incidence of FAP, as reported in many epidemiology based reports varies from 1 in 7,000 to 1 in 22,000 individuals. About 30% of people with FAP do not have any family history of the condition; they have a de novo (new) mutation in the APC gene. Males and Females are equally affected (1:1) by FAP and reported in all races. The average age of onset of polyposis in FAP is 16 (range 7-36 years) years, whereas by age 35 years, 95% of individuals with FAP have polyps; without colectomy, colon cancer is unavoidable.
In January 2017, Marina Biotech was granted European claims covering Bacteria Mediated Gene Silencing (EP 08768475.9, European Patent 2173875), which claims the company’s tkRNAi technology being utilized in its CEQ508 program that is being developed to treat FAP. Previously in 2015, the U.S. Food and Drug Administration (FDA) have granted Fast Track designation to CEQ508, for the treatment of FAP. There are around 7 drugs in pipeline being investigated in different stage of development for FAP. A few projects for FAP, such as development of Ursodeoxycholic by Aptalis have been put on hold (dormant) due to some undisclosed reasons. Whereas, the development of Exisulind by OSI Pharmaceuticals and Valproic acid by Onxeo SA has now been discontinued.
Despite rigorous investigation by researchers to develop a reliable therapeutic to treat patients with FAP, there remains significant unmet medical needs. The long-term and frequent assessment and interventions even after radical colectomy, represent one of the major unmet medical needs. Modest Efficacy measured by reduction in the number (and size) of polyps demonstrated with current therapies is also a matter of concern for the researchers that needs to be addressed soon.