On January 4, 2017 CytRx Corporation (NASDAQ: CYTR), a clinical-stage biopharmaceutical company focused on discovering, developing and commercializing new therapeutics to treat patients with cancer, reported that, in response to a request from the company, the U.S. Food and Drug Administration (FDA) has agreed to a Type B pre-NDA meeting at which the company will seek input on its planned New Drug Application (NDA) for aldoxorubicin as a new second-line treatment for patients with soft tissue sarcomas (STS) (Press release, CytRx, JAN 4, 2017, View Source [SID1234517261]). Assuming a positive outcome from this pre-NDA meeting, CytRx expects to submit an NDA for aldoxorubicin to the FDA in the last quarter of 2017, and, subject to FDA approval, bring aldoxorubicin to market next year.

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"Based on positive, statistically significant results from our pivotal Phase 3 trial evaluating aldoxorubicin compared to investigator’s choice in patients with previously treated relapsed or refractory sarcomas, we requested, and were recently granted, a Type B meeting with the FDA," said Daniel Levitt, M.D., Ph.D., Chief Operating Officer and Chief Medical Officer of CytRx. "The purpose of this meeting is to share the Phase 3 data with the Agency and discuss the regulatory path forward for aldoxorubicin. In our view, this meeting is an important next step toward our goal of bringing aldoxorubicin to the thousands of patients in need of a new treatment for relapsed soft tissue sarcoma."

Overview of the Updated Phase 3 Trial and Results

The randomized, controlled Phase 3 trial enrolled a total of 433 patients at 79 clinical sites. Patients with metastatic, locally advanced or unresectable soft tissue sarcomas who had either not responded to, or who had progressed following treatment with one or more systemic regimens of non-adjuvant chemotherapy were randomized 1:1 to be treated with aldoxorubicin or the investigator’s choice of an approved chemotherapeutic regimen, including doxorubicin, ifosfamide, dacarbazine, pazopanib (Votrient), or gemcitabine plus docetaxel. The primary endpoint of the study is PFS. Secondary endpoints include overall survival, response rates, disease control rates and safety.

In November 2016, CytRx reported positive results which demonstrated a statistically significant improvement in progression-free survival (PFS) between aldoxorubicin and investigator’s choice therapy in 246 patients with leiomyosarcoma and liposarcoma, (p=0.007). The hazard ratio (HR) was 0.62 (95% CI 0.44-0.88), representing a 38% reduction in the risk of tumor progression for patients receiving aldoxorubicin versus investigator’s choice. Leiomyosarcoma and liposarcoma are the two most common types of STS and accounted for 57% of the patients enrolled in the trial. Aldoxorubicin also demonstrated a statistically significant improvement in PFS over investigator’s choice in 312 patients treated in North America (p=0.028; HR=0.71, 95% CI 0.53-0.97). Notably, aldoxorubicin performed better than investigator’s choice for the entire study population and narrowly missed statistical significance (p=0.12; HR=0.81, 95% CI 0.64-1.06). All responses were determined by an independent, blinded central lab assessment of scans.

Aldoxorubicin did not cause clinically significant cardiac, renal, or hepatic toxicities. For the global trial population, the most commonly reported adverse events were neutropenia and anemia consistent with prior clinical trials with aldoxorubicin. Grade 3 or higher adverse events were manageable with supportive care and occurred at a rate of 61% for patients receiving aldoxorubicin and 46% in patients treated with investigator’s choice. Importantly, treatment-emergent adverse events leading to discontinuation occurred in 4.2% of patients treated with aldoxorubicin, compared to 6.3% for patients receiving investigator’s choice.

Patients continue to be followed for overall survival (OS), a secondary endpoint, and CytRx expects the OS data to be available in 2017.

About Soft Tissue Sarcoma

Soft tissue sarcoma is a cancer occurring in muscle, fat, blood vessels, tendons, fibrous tissues and connective tissue. It can arise anywhere in the body at any age. STS remains a high unmet medical need because of the difficulty in treating the more than 50 types of this aggressive cancer. According to the American Cancer Society, in 2016 more than 12,300 new cases were diagnosed in the U.S. and approximately 5,000 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

Aldoxorubicin is a rationally-engineered cytotoxic which combines doxorubicin, a widely used chemotherapeutic agent, with a novel linker molecule that binds directly and specifically to circulating albumin, the most abundant protein in the bloodstream. Protein-hungry tumors concentrate albumin, which facilitates 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. Typically, 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. Using this acid-sensitive linker technology, aldoxorubicin delivers greater doses of doxorubicin (3 ½ to 4 times). To date, there has been no evidence of clinically significant effects of aldoxorubicin on heart muscle, even at cumulative doses of drug well in excess of 6,500 mg/m2 of doxorubicin equivalents. Aldoxorubicin is the first-ever single agent to show superiority over doxorubicin in a randomized clinical trial in first-line STS.