CytRx Corporation's oncology pipeline includes three clinical-stage drug candidates in various stages of development, including:
Tamibarotene (formerly known as TM-411, TOS-80T, Am-80, and INNO-507) is an orally available, rationally designed, synthetic retinoid compound which was designed to potentially avoid toxic side effects by binding to its molecular target more selectively than all trans-retinoic acid (ATRA), the current first line treatment for APL. There is a Special Protocol Assessment (SPA) in place with the FDA for a Phase 2 registration clinical trial, known as STAR-1, which is evaluating the efficacy and safety of tamibarotene as a third-line treatment for APL. The STAR-1 trial is ongoing and currently includes seven clinical sites in the U.S. CytRx recently reported that, of the 11 patients enrolled in the STAR-1 trial to date, 5 patients, or 45%, achieved a morphologic leukemia-free state, or MLFS. Of those, two patients have achieved durable complete response and one has achieved morphologic leukemia-free state, or MLFS, but withdrew from the trial to receive a bone marrow transplant before the durable complete response could be confirmed. One patient achieved a complete response, but did not maintain MLFS for the required 28 days to be considered a durable complete response. Another patient achieved a durable MLFS, but did not have the necessary increases in blood cells to be considered a durable complete response. CytRx holds the North American and European rights to tamibarotene as a treatment for APL.
The FDA has granted Orphan Drug Designation for APL and Fast Track Designation for the use of tamibarotene in patients with relapsed or refractory APL following treatment with all-trans retinoic acid (ATRA) and arsenic trioxide. In addition, tamibarotene has been granted orphan medicinal product status by the European Medicines Agency for the treatment of APL. The efficacy of orally-administered tamibarotene was demonstrated in two Phase 2 studies conducted in Japan in a total of 63 Japanese subjects with APL. The overall complete response rate in these subjects was 60%. In subjects experiencing their first relapse, the overall complete response rate was 81%.
APL is diagnosed in approximately 1,500 new patients in the United States annually. The near-term market opportunity for CytRx’s tamibarotene in refractory APL in the U.S. alone is estimated to approach $20 million per year - with the market opportunity for an expanded label including refractory, maintenance and front-line therapy increasing to $150 million in potential recurring revenue in the U.S. and Europe. There are currently no approved third-line treatment options for refractory APL patients.
Tamibarotene has also showed statistically significant anti-tumor activity in animal trial for multiple myeloma, an incurable malignant tumor of the plasma cells of bone marrow. CytRx retains an option to expand its licenses for the use of tamibarotene in other fields in oncology, including multiple myeloma, myelodysplastic syndrome and certain solid tumors in the U.S., and multiple myeloma, myelodysplastic syndromes and solid tumors other than hepatocellular carcinoma in Europe.
INNO-206 (formerly DOXO-EMCH) is a prodrug of the commonly prescribed chemotherapeutic doxorubicin and was designed to reduce adverse events by controlling release and preferentially targeting the tumor. In a Phase 1 study, doses were administered at up to six times the standard dosing of doxorubicin without an increase in observed side effects over those historically seen with doxorubicin. Objective clinical responses were seen in patients with sarcoma, breast and lung cancers. In addition, the Company has announced that INNO-206 has demonstrated statistically significant results in animal models of breast cancer, pancreatic cancer and ovarian cancer. The Company is evaluating options for a Phase 2 protocol with the FDA.
INNO-406 (formerly known as NS-187) is a potent, orally available, rationally designed, dual Bcr-Abl and Lyn-kinase inhibitor that is currently being planned as a third line treatment for patients with Chronic Myeloid Leukemia (CML) or certain forms of Acute Myeloid Leukemia (AML) that are refractory or intolerant of other approved treatments. In November 2008, CytRx announced that bafetinib demonstrated clinical responses in patients with CML in an international Phase I dose-ranging clinical trial conducted in patients with CML and other leukemias that have a certain mutation called the Philadelphia Chromosome (Ph+) and are intolerant of or resistant to Gleevec and, in some cases, second-line tyrosine kinase inhibitors such as dasatiniband nilotinib). INNO-406 has been granted Orphan Drug Status for the treatment of Philadelphia chromosome-positive (Ph+) CML by the FDA.
