LOS ANGELES — CytRx Corporation (NASDAQ:CYTR), a biopharmaceutical research and development company engaged in the development of high-value human therapeutics, today announced that tamibarotene, currently under evaluation in a U.S. registration trial as a third-line treatment for acute promyelocytic leukemia (APL), showed statistically significant anti-tumor activity in human myeloma cells transplanted into animals.
Multiple myeloma is an incurable malignant tumor of the plasma cells of bone marrow. Results of the trial were published in the June 2009 peer-reviewed journal Cancer Science (Volume 100, No. 6, Pages 1137-1143).
“These results support our contention that tamibarotene’s mechanism of action may provide broad commercial potential as a therapeutic treatment beyond APL to other cancers such as multiple myeloma,” said Steven A. Kriegsman, CytRx President and CEO. “Despite advances in therapies that improve the quality of life and length of survival, many multiple myeloma patients experience severe side effects from current therapies, prompting the need for additional therapies.”
“We are evaluating opportunities for a Phase 2 clinical program with tamibarotene as a multiple myeloma therapy, as well as investigating partnership prospects for developing and commercializing tamibarotene in the U.S. for both multiple myeloma and APL,” he added.
CytRx has the right to develop tamibarotene as a treatment for multiple myeloma in Europe, and has the option to expand its license for the use of tamibarotene for multiple myeloma and certain other oncology applications in the U.S. Tamibarotene is currently approved for relapsed or refractory treatment of APL in Japan.
The animal trial, conducted by an independent third party in Japan, was designed to evaluate the activity of tamibarotene as a multiple myeloma treatment alone and in combination with a glucocorticoid, a commonly prescribed treatment for this disease. Five different human myeloma cell lines were treated with tamibarotene alone, glucocorticoids alone, or tamibarotene + glucocorticoids in cell culture. Tamibarotene by itself inhibited the growth of these tumor cells two- to 10-fold more potently than all-trans retinoic acid (ATRA), a less specific relative of tamibarotene which has previously been shown to inhibit the growth of human myeloma cells. Importantly, the combination of tamibarotene with glucocorticoids was found to show markedly greater growth inhibition than either drug alone.
Human myeloma cells were then transplanted into mice with compromised immune systems to study the tumor growth-inhibitory effects of these drugs. Both tamibarotene and glucocorticoids by themselves reduced the rate of tumor growth. However, the combination of tamibarotene with glucocorticoids showed a synergistic interaction that resulted in markedly decreased tumor growth and increased survival compared with either drug alone. Trial investigators concluded that tamibarotene in this drug combination approach was among the most promising potential therapeutic regimens for multiple myeloma, especially in high-risk patients, and should be further investigated.
“Our drug tamibarotene is more stable and may have fewer adverse events than ATRA, with both drugs demonstrating the ability to force certain types of leukemia cells to cease growing uncontrollably and return to performing their normal functions – a process known as terminal differentiation,” said Jack Barber Ph.D., CytRx’s Chief Scientific Officer. “Multiple myeloma cells are thought to grow uncontrollably due in part to a growth factor called IL-6. Glucocorticoids are a potent inducer of cell death; however this benefit may be offset by their known activation of IL-6 activity. Tamibarotene has previously shown the ability to interfere with the normal functioning of IL-6, which could be the foundation for the anti-proliferative effects of tamibarotene in multiple myeloma, particularly in combination with glucocorticoids.
“We are delighted and encouraged by this proof of concept, which could ultimately increase the potential market for tamibarotene,” added Dr. Barber.
About Multiple Myeloma
Multiple myeloma is the second most common hematologic malignancy in the U.S. According the National Cancer Institute, an estimated 20,580 new cases of multiple myeloma will be diagnosed in the U.S., and 10,580 multiple myeloma patient deaths will be recorded in 2009. According to industry leading researcher Mattson Jack Group, currently in the top seven markets (including the U.S., EU and Japan), the number of new cases each year is expected to total more than 43,500. The average five-year survival is 35 percent and the American Cancer Society found multiple myeloma to be the sixth deadliest cancer in terms of a mortality-to-incidence ratio.
Multiple myeloma is characterized by malignant plasma cells that form tumors in the bone marrow. These plasma cell tumors can spread throughout the bone marrow, thereby disrupting the production of red blood cells and platelets, which normally occur in the bone marrow. Excessive amounts of malignant plasma cells also may decrease the number of white blood cells, which are important in fighting off infections.
Tamibarotene is an orally available, rationally designed, synthetic retinoid compound 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. A Special Protocol Assessment (SPA) is in place with the U.S. Food and Drug Administration (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 30 clinical sites, 22 of which are in Europe, and one in Canada. CytRx believes that successful data from the STAR-1 trial and supporting studies, in conjunction with data from the Japanese clinical trials, will form the basis for a New Drug Application (NDA).
The FDA has granted Orphan Drug Designation 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. 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%. In addition to multiple myeloma, CytRx also retains an option to expand its licenses for the use of tamibarotene in other fields in oncology, including myelodysplastic syndrome and certain solid tumors in the U.S., and myelodysplastic syndromes and solid tumors other than hepatocellular carcinoma in Europe.
About CytRx Corporation
CytRx Corporation is a biopharmaceutical research and development company engaged in the development of high-value human therapeutics. The CytRx drug development pipeline includes programs in clinical development for cancer indications, including tamibarotene in a registration study for the treatment of acute promyelocytic leukemia (APL). In addition, CytRx is developing two drug candidates based on its industry-leading molecular chaperone technology, which aims to repair or degrade misfolded proteins associated with disease. CytRx also maintains a 45% equity interest in publicly traded RXi Pharmaceuticals, Inc. (NASDAQ:RXII). For more information on the Company, visit www.cytrx.com.
This press release contains forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended. Such statements involve risks and uncertainties that could cause actual events or results to differ materially from the events or results described in the forward-looking statements, including risks relating to the timing, outcome or results of any future pre-clinical or clinical testing of tamibarotene as a treatment for multiple myeloma, risks related to CytRx’s ability to manufacture its drug candidates, including tamibarotene, in commercial quantities in compliance with stringent regulatory requirements, risks related to CytRx’s ability to enter into partnerships or other transactions to advance the clinical development of its portfolio of drug candidates, risks related to CytRx’s need for additional capital or strategic partnerships to fund its ongoing working capital needs and development efforts, risks related to the future market value of CytRx’s investment in RXi and the liquidity of that investment, and the risks and uncertainties described in the most recent annual and quarterly reports filed by CytRx with the Securities and Exchange Commission and current reports filed since the date of CytRx’s most recent annual report. All forward-looking statements are based upon information available to CytRx on the date the statements are first published. CytRx undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.
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