CytRx Corporation (Nasdaq:CYTR), a biopharmaceutical research and development company specializing in oncology, today announced that positive preclinical results from an in vivo study of aldoxorubicin in an animal model of glioblastoma will be presented at the American Association for Cancer Research Annual Meeting being held April 5-9, 2014 in San Diego, CA. CytRx announced data from the trial, which demonstrated that aldoxorubicin significantly increased survival almost 2½ fold compared to doxorubicin treatment in an in vivo xenograft tumor model employing growth of human glioblastoma multiforme (GBM) tumors in mouse brains. Aldoxorubicin, but not doxorubicin, also demonstrated preferential accumulation and prolonged retention in the tumor tissue. These data, combined with aldoxorubicin’s favorable safety profile, support the current evaluation of aldoxorubicin as a treatment for patients with GBM tumors. “In addition to the clear survival benefit seen in the aldoxorubicin-treated animals, we also saw significant tumor regression and evidence of drug retention inside the tumors,” said Om Prakash, Ph.D., Research Professor of Medicine, Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, the study’s principal investigator, and the poster presenter. “Aldoxorubicin also significantly reduced the number of dividing cells within the tumors and showed a statistically relevant increased expression of apoptosis biomarkers. In comparison, doxorubicin did not appear to enter the tumor to any significant degree and showed no efficacy greater than saline in the treatment of these brain tumors.” CytRx is currently conducting a Phase 2 clinical trial evaluating aldoxorubicin in patients with late-stage GBM. In late 2013, the Company reported highly statistically significant results from its global Phase 2b clinical trial evaluating aldoxorubicin as a first-line therapy in patients with soft tissue sarcomas. In this trial, aldoxorubicin demonstrated 80-100% superiority over doxorubicin in progression-free survival (PFS). Median PFS, 6-month PFS and overall response rates all significantly favored aldoxorubicin treatment over doxorubicin. Aldoxorubicin is also being studied in a Phase 2 clinical trial in HIV-related Kaposi’s sarcoma. CytRx also has initiated, under a special protocol assessment, a pivotal Phase 3 global trial with aldoxorubicin as a therapy for patients with soft tissue sarcomas.
|Poster presentation details:|
|Poster Title: Antitumor efficacy of a novel anthracycline derivative aldoxorubicin in an orthotopic mouse model of glioblastoma|
|Abstract #: 816|
|Date and Time: Sunday, April 6, 2014 from 1:00 to 5:00 PM PT|
|Session ID: Experimental and Molecular Therapeutics 6|
|Location: Hall A-E, Poster section 34|
|Summary of the data: GBM is the most common and malignant of all primary brain tumors with a median survival of only 12-15 months despite standard-of-care treatments like surgical resection, radiotherapy, and chemotherapy. This study evaluated the preclinical efficacy of aldoxorubicin, a novel albumin-binding prodrug of doxorubicin, for the treatment of GBM in a murine model, and compared its antitumor effect with doxorubicin. Human glioma cells were injected in vivo into the left striatum. After 12 days, mice (n=8 in each group) received either vehicle (saline), a single intravenous injection of aldoxorubicin (24 mg/kg) or doxorubicin (6 mg/kg) once a week. The study results demonstrated that the animals treated with aldoxorubicin had a median survival of more than 60 days, compared to 26 days for the control animals or those treated with doxorubicin. The aldoxorubicin treated animals also demonstrated tumor regression. Fluorescence microscopy showed selective accumulation of aldoxorubicin, but not doxorubicin, in the tumor tissues resected from tumor-bearing mice 24h following intravenous injection of these drugs. HPLC analysis revealed 3- to 4-fold higher aldoxorubicin retention in the tumor tissues than in the surrounding brain tissues. Immunohistochemical evaluation of aldoxorubicin-treated tumors showed that the drug also significantly decreased the number of dividing cells and activated the apoptosis effector cleaved caspase-3.|
About AldoxorubicinThe widely used chemotherapeutic agent doxorubicin is delivered systemically and is highly toxic, which limits its dose to a level below its maximum therapeutic benefit. Doxorubicin also is associated with many side effects, especially the potential for damage to heart muscle at cumulative doses greater than 450 mg/m2. Aldoxorubicin combines doxorubicin with a novel single-molecule linker that binds directly and specifically to circulating albumin, the most plentiful protein in the bloodstream. Protein-hungry tumors concentrate albumin, thus increasing the delivery of the linker molecule with the attached doxorubicin to tumor sites. In the acidic environment of the tumor, but not the neutral environment of healthy tissues, doxorubicin is released. This allows for greater doses (3½ to 4 times) of doxorubicin to be administered while reducing its toxic side effects. In studies thus far there has been no evidence of clinically significant effects of aldoxorubicin on heart muscle, even at cumulative doses of drug well in excess of 2 g/m2. About CytRx Corporation CytRx Corporation is a biopharmaceutical research and development company specializing in oncology. CytRx currently is focused on the clinical development of aldoxorubicin (formerly known as INNO-206), its improved version of the widely used chemotherapeutic agent doxorubicin. CytRx has completed a global Phase 2b clinical trial with aldoxorubicin as a first-line therapy for soft tissue sarcomas, a Phase 1b/2 clinical trial primarily in the same indication, a Phase 1b study of aldoxorubicin in combination with doxorubicin in patients with advanced solid tumors and a Phase 1b pharmacokinetics clinical trial in patients with metastatic solid tumors. CytRx has initiated under a special protocol assessment a pivotal Phase 3 global trial with aldoxorubicin as a therapy for patients with soft tissue sarcomas whose tumors have progressed following treatment with chemotherapy, and recently announced that it has received approval from the FDA to continue dosing patients with aldoxorubicin until disease progression in that clinical trial. CytRx has initiated a Phase 2 clinical trial with aldoxorubicin in patients with late-stage glioblastoma (brain cancer), and a Phase 2 clinical trial in HIV-related Kaposi’s sarcoma. CytRx plans to expand its pipeline of oncology candidates based on a linker platform technology that can be utilized with multiple chemotherapeutic agents and may allow for greater concentration of drug at tumor sites. CytRx also has rights to two additional drug candidates, tamibarotene and bafetinib. CytRx completed its evaluation of bafetinib in the ENABLE Phase 2 clinical trial in high-risk B-cell chronic lymphocytic leukemia (B-CLL), and plans to seek a partner for further development of bafetinib. For more information about CytRx Corporation, visit www.cytrx.com. Forward-Looking Statements 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 outcome, timing and results of CytRx's clinical trials, the risk that any future human testing of aldoxorubicin might not produce results similar to those seen in past human or animal testing, risks related to CytRx's ability to manufacture its drug candidates in a timely fashion, cost-effectively or in commercial quantities in compliance with stringent regulatory requirements, risks related to CytRx's need for additional capital or strategic partnerships to fund its ongoing working capital needs and development efforts, including the Phase 3 clinical development of aldoxorubicin, 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.