Anthracyclines are a class of drugs that are among the most commonly used agents in the treatment of cancer. Doxorubicin, the first anthracycline to gain approval, has demonstrated efficacy in a wide variety of cancers including breast cancer, lung cancer, sarcomas, and lymphomas. However, doxorubicin is associated with side effects such as myelosuppression, gastrointestinal disorders, mucositis, stomatitis, cumulative cardiotoxicity and extravasation.
INNO-206 (formerly DOXO-EMCH) is a prodrug for doxorubicin. Specifically, it is the (6-Maleimidocaproyl) hydrazone of doxorubicin. Essentially, this chemical name describes doxorubicin (DOXO) attached to an acid sensitive linker (EMCH). We believe this novel agent has attributes that improve on native doxorubicin including reduction of adverse events, improvement in efficacy and the ability to reach the tumor more quickly.
The proposed mechanism of action is as follows:
- After administration, INNO-206 rapidly binds endogenous circulating albumin through the EMCH linker
- Circulating albumin preferentially accumulates in tumors, bypassing uptake by other non-specific sites including heart, bone marrow and gastrointestinal tract
- Once albumin-bound INNO-206 reaches the tumor, the acidic environment of the tumor causes cleavage of the acid sensitive linker
- Free doxorubicin is released at the site of the tumor
In preclinical models, INNO-206 was superior to doxorubicin with regard to ability to increase dosing, antitumor efficacy and safety. A Phase I study of INNO-206 that demonstrated safety and objective clinical responses in a variety of tumor types was completed in the beginning of 2006 and presented at the March 2006 Krebskongress meeting in Berlin. In this study, doses were administered at up to 4 times the standard dosing of doxorubicin without an increase in observed side effects over historically seen levels. Objective clinical responses were seen in patients with sarcoma, breast, and lung cancers.
CytRx has recently announced the planned initiation of three open label Phase 2 clinical trials with INNO-206. Because each of the clinical trials will be open label, CytRx expects to be able to review data from the trials on an ongoing basis.
Pancreatic Cancer
This month, CytRx announced that the Tumor Biology Center, Freiburg, Germany, plans to initiate a Phase 2 open-label clinical trial with INNO-206 as a treatment for patients with advanced pancreatic cancer in the first half of 2010. CytRx will supply INNO-206 for the clinical trial. Worldwide, pancreatic cancer is the eighth leading cause of cancer death, and it ranks thirteenth in cancer incidence. The median survival for patients with pancreatic cancer is typically four to six months, with a one-year survival rate of 24% and five-year survival rate of approximately 5%.
Gastric (Stomach Cancer)
In November 2009, CytRx announced plans to conduct an open-label, multinational Phase 2 clinical trial with INNO-206 as a second-line treatment in patients with advanced gastric (stomach) cancer beginning in the second half of 2010. Gastric cancer claims 800,000 lives annually making it the second leading cause of cancer deaths worldwide.
Soft-Tissue Sarcoma
Also in November 2009, the Company announced plans to initiate in the second half of 2010 a multinational Phase 2 clinical trial with INNO-206 as a treatment for patients with advanced soft tissue sarcomas who have failed surgery and radiation. Worldwide, approximately 25,000 new cases of soft tissue sarcomas are reported and about 10,000 deaths are attributed to this cancer each year.
