SN2310 is a novel camptothecin for the treatment of cancer. Camptothecins are potent anticancer agents that belong to the family of drugs called topoisomerase I inhibitors that bind reversibly to the TOPO-I-DNA complex causing breaks in the DNA strands during replication resulting in cell death.
There are two camptothecins approved by the FDA: irinotecan (Camptosar) and topotecan (Hycamtin). Irinotecan is approved for the treatment of metastatic colorectal cancer when used as a component of first-line therapy with 5-FU and leucovorin or when disease has recurred or progressed following initial 5-FU- based therapy. Topotecan is approved for second-line treatment of ovarian cancer and small-cell lung cancer. The combined sales of the two drugs were over $1 billion in 2006, with irinotecan sales of over $900 million.
SN-38 is the active metabolite of irinotecan. A major limitation of irinotecan is that the pro-drug requires enzymatic hydrolysis to the active drug, SN-38, and only approximately 3% is hydrolyzed. Based on literature reports, SN-38 is 200 to 2000 times more cytotoxic than irinotecan. SN-38 has not been successfully developed, at least in part due to its poor solubility.
SN2310 Injectable Emulsion is an oil-and-water emulsion that incorporates a new derivative of SN-38, SN2310. The conjugation of SN-38 to Vitamin E succinate enables increased solubility in a vitamin E-based, oil-in-water emulsion that can be administered without dilution. The difference in the structure is shown in the right sidebar.
SN2310 Injectable Emulsion is being developed with the objective of demonstrating improved anti-tumor activity as a result of increased exposure to SN-38 based on a longer half-life. In addition, the product is more convenient, with a shorter duration of administration and no requirement for reconstitution.
In preclinical studies, comparable or better cytotoxic activity in vitro was observed when results after administration of SN2310 were compared to results after administration of irinotecan or topotecan. Similarly, the anti-tumor activity of SN2310 was comparable or better than activity of irinotecan when compared in human tumor xenograft studies. To-date, we have demonstrated that SN2310 provides similar exposure of SN38 as irinotecan at approximately a 15-fold lower dose, with a half-life that is approximately seven-fold higher. Additionally, the Vitamin E chain is separated from SN38 via both enzymatic and hydrolytic cleavage, and in vitro studies suggest that this results in conversion of about 10 times more prodrug to active drug than irinotecan.
In September 2006, Sonus initiated a Phase 1 study of SN2310 which is presently ongoing.
