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TMCNet:  CytRx Receives FDA Approval to Extend Aldoxorubicin Dosing Cycles until Disease Progression in Upcoming Pivotal, Global Phase 3 Trial for Soft Tissue Sarcomas

[January 21, 2014]

CytRx Receives FDA Approval to Extend Aldoxorubicin Dosing Cycles until Disease Progression in Upcoming Pivotal, Global Phase 3 Trial for Soft Tissue Sarcomas

LOS ANGELES --(Business Wire)--

CytRx Corporation (NASDAQ:CYTR), a biopharmaceutical research and development company specializing in oncology, today announced it has received approval from the U.S. Food and Drug Administration (FDA) to continue dosing patients with aldoxorubicin until disease progression in a planned pivotal, global Phase 3 clinical trial with aldoxorubicin as a second-line treatment for soft tissue sarcomas. The clinical trial is scheduled to begin this quarter. For purposes of the clinical trial, disease progression is defined as an increase in the size of measurable tumors by 20% or the development of a new tumor lesion. The following table sets forth the cumulative dose of doxorubicin in prior and planned CytRx clinical trials:




     
       

Cumulative Doxorubicin Dose

Recognized maximum dose associated with cardiac toxicity - Doxorubicin

      450 mg/m2

CytRx Phase 2b Clinical Trial - Aldoxorubicin

      1,560 mg/m2

CytRx Phase 1b/2 Clinical Trial- Aldoxorubicin

      2,080 mg/m2

CytRx Pharmacokinetics Clinical Trial - Aldoxorubicin

      1600-3200 mg/m2

CytRx Pivotal Phase 3 Clinical Trial- Aldoxorubicin

      Up to Disease Progression
 

The study design under the trial's Special Protocol Assessment (SPA) originally called for dosing to be stopped after six treatment cycles. FDA acceptance of a protocol amendment to include a dose-to-progression regimen demonstrates the superior cardiac safety thus far of administrating a cumulative 2,080 mg/m2 dose of aldoxorubicin as seen in the Company's recently announced global, Phase 2b clinical trial results (which is equivalent to 1,560 mg/m2 of doxorubicin), which is 3.5 times the recognized maximum cumulative dose of doxorubicin (450 mg/m2) associated with cardiac toxicity (heart damage).

Sant Chawla, M.D., of the Sarcoma Oncology Center in Santa Monica, Calif., and principal investigator of the Phase 3 pivotal trial, commented, "In addition to observing no significant cardiotoxicity of aldoxorubicin to this point, the FDA's agreement to extend dosing beyond six cycles offers the potential to achieve even greater progression-free survival efficacy results than were demonstrated in CytRx's recent highly successful global Phase 2b trial for advanced soft tissue sarcomas. As the principal investigator for this trial, I can say that we are very pleased to have the opportunity to provide the maximum benefits of aldoxorubicin to the patients around the world."

"Current chemotherapy treatments for soft tissue sarcomas have demonstrated limited impact, and other potential treatments have provided no improved benefits in Phase 3 trials," said CytRx President and CEO Steven A. Kriegsman. "As such there is a significant need for a second-line treatment with greater efficacy and reduced or no measurable cardiac toxicity. This FDA acceptance of extended dosing represents a potential major breakthrough for CytRx and STS patients throughout the world."

The international, open-label pivotal Phase 3 clinical trial will enroll approximately 400 patients with metastatic, locally advanced or unresectable soft tissue sarcomas who have either not responded to or have progressed following treatment with one or more systemic regimens of non-adjuvant chemotherapies. Trial patients will be randomized 1:1 to be treated with aldoxorubicin or the investigator's choice of an approved chemotherapeutic regimen to include dacarbazine, pazopanib (Votrient®), gemcitabine plus docetaxel, doxorubicin or ifosfamide, with up to three comparator regimens to be selected by the investigator at each clinical site. The clinical trial will be conducted at approximately 100 clinical sites in the U.S., Europe, Canada, Latin America and Australia. The primary endpoint of the study is progression-free survival (PFS), and secondary endpoints include overall survival and safety.

Review of Results for Phase 2b Trial with Aldoxorubicin as a First-line Treatment in Advanced Soft Tissue Sarcomas

As initially reported on December 11, 2013, patients treated with aldoxorubicin demonstrated highly statistically significant clinical outcomes compared to those receiving standard doxorubicin therapy for soft tissue sarcomas in both an investigator assessment and a central lab review. Specifically, both assessments showed an unambiguous 80% to 100% improvement in PFS among patients treated with aldoxorubicin.

In an intent-to-treat analysis, the investigator-assessed median PFS was 8.4 months for aldoxorubicin patients versus 4.7 months for doxorubicin patients (p=0.0002), while the blinded central lab review indicated that median PFS for aldoxorubicin patients was 5.7 months versus 2.8 months for doxorubicin patients (p=0.018). Per investigators, 67.1% of aldoxorubicin patients had not progressed at 6 months, compared with 36.1% of doxorubicin-treated patients (p=0.005). By blinded central lab review, 46.8% of aldoxorubicin patients had not progressed at 6 months, compared with 23.7% of doxorubicin patients (p=0.038).

On January 8, 2014, CytRx reported results of additional analyses that determined hazard ratios for the primary endpoint of PFS by both investigators at study sites and by a blinded radiology review performed at an independent central laboratory. The hazard ratio for investigator-read scans was 0.37 (95% confidence interval, range of 0.212 to 0.643) (p=0.0004), reflecting a 63% reduction in the risk of disease progression; and the hazard ratio for central lab scans was 0.59 (95% confidence interval, range of 0.36 to 0.96) (p=0.034), reflecting a 41% reduction in the risk of disease progression. Hazard ratios - the likelihood that the study endpoint (in this case tumor progression) will be reached during a given period - are an important measure of the reliability and uniformity of the absolute data for PFS as presented above. Hazard ratios where the upper limit is less than 1 indicate that there is a significant difference between the two study groups.

CytRx also reported that a Kaplan-Meier analysis of the trial results, which describes the time it takes for tumors to progress in individual patients, showed significant improvement in patients treated with aldoxorubicin versus patients treated with doxorubicin.

About Soft Tissue Sarcoma

Soft tissue sarcoma is a cancer occurring in muscle, fat, blood vessels, tendons, fibrous tissues and connective tissue, and can arise anywhere in the body at any age. According to the American Cancer Society, there are approximately 50 types of soft tissue sarcomas. In 2013 more than 11,400 new cases were diagnosed in the U.S. and approximately 4,400 Americans died from this disease. In addition, approximately 40,000 new cases and 13,000 deaths in the U.S. and Europe are part of a growing underserved market.

About Aldoxorubicin

The 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 plans to initiate 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. CytRx has initiated a Phase 2 clinical trial with aldoxorubicin in patients with late-stage glioblastoma (brain cancer), and plans to initiate 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 the results of any future human testing of aldoxorubicin, including the final data from the Phase 2b clinical testing of aldoxorubicin as a first-line treatment in patients with metastatic, locally advanced or unresectable soft tissue sarcomas who have not been previously treated with any chemotherapy, or the Phase 3 clinical trial with aldoxorubicin as a second-line treatment for advanced soft tissue sarcomas, might not produce objective response or safety results similar to the data described in this press release, 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.


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