LOS ANGELES, June 8, 2017 /PRNewswire/ -- CytRx Corporation (NASDAQ: CYTR) a biopharmaceutical research and development company specializing in oncology, today announced an update on the regulatory pathway for a New Drug Application (NDA) submission for aldoxorubicin in soft tissue sarcomas (STS).
The Company plans to submit a rolling NDA under section 505(b)(2) to the FDA for aldoxorubicin as a treatment for STS. The 505(b)(2) pathway is designed for a new drug that contains the same active ingredient as a previously approved drug, also known as a reference drug. For aldoxorubicin, doxorubicin is the reference drug. The NDA submission is not reliant solely on the recently completed Phase 3 clinical trial in STS or overall survival results. Rather, CytRx's completed pharmacokinetic clinical trial, Phase 2b and Phase 3 trials in STS, along with preclinical safety and efficacy studies, will serve as "scientific bridges" between aldoxorubicin and doxorubicin. These studies, along with the published literature of doxorubicin's effectiveness and safety, will form the basis of the NDA filing for aldoxorubicin under the 505(b)(2) regulations.
"Having worked on aldoxorubicin's regulatory strategy and as a participant in the March FDA meeting, the 505(b)(2) regulatory pathway is the most appropriate for aldoxorubicin in STS," said Scott Wieland, PhD, CytRx's Senior Vice President of Drug Development. "As noted in the FDA meeting, the aldoxorubicin preclinical and clinical studies will support a 505(b)(2) NDA submission, and no new clinical trials were requested by the FDA at the meeting. Additionally, CytRx's previously approved special protocol assessment is no longer applicable."
Aldoxorubicin has received Orphan Drug Designation by the FDA for the treatment of STS. Orphan designation provides several benefits including seven years of market exclusivity after approval, certain R&D related tax credits and protocol assistance by the FDA. European regulators granted aldoxorubicin Orphan Medicinal Product Designation for STS which confers ten years of market exclusivity among other benefits. CytRx plans to discuss with the European Medicines Agency (EMA) a path to filing a Marketing Authorization Application (MAA).
The proposed product label would allow the treatment of soft tissue sarcomas. New data could support future use of aldoxorubicin in neoadjuvant (pre-surgery) settings, as well as a replacement for doxorubicin in chemotherapy combinations. CytRx is also working on a market expansion strategy which would include other indications for aldoxorubicin including combinations with other chemotherapeutics and immunotherapies.
About a 505(b)(2) New Drug Application
A new drug application (NDA) under the Food and Drug Administration's (FDA) section 505(b)(2) is for a new drug containing the same active ingredient as a previously approved drug. According to the publication Regulatory Focus (Reg Focus, Apr. 2010, 8-13.), a drug reviewed under 505(b)(2) represents a modified version of a previously approved product that requires additional clinical and nonclinical studies, other than bioavailability/bioequivalence studies, to demonstrate its safety and efficacy. Such an application differs from a typical NDA in that the sponsor can rely on, at least in part, the FDA's findings of safety and effectiveness for the previously approved reference drug.
About the Phase 2b and Phase 3 Clinical Trials
The global Phase 2b trial involved 123 patients at 31 sites. Patients with advanced soft tissue sarcomas were randomized 2:1 to receive either 350 mg/m2 of aldoxorubicin (83 patients) or 75 mg/m2 of doxorubicin (40 patients) every 3 weeks for up to 6 cycles. The trial was designed to compare aldoxorubicin directly with doxorubicin.
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 350 mg/m2 of aldoxorubicin until disease progression or the investigator's choice of an approved chemotherapeutic regimen, including doxorubicin, ifosfamide, dacarbazine, pazopanib (Votrient®), or gemcitabine plus docetaxel.
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 2017 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 the drug well in excess of 5,000 mg/m2. Aldoxorubicin is the first-ever single agent to show superiority over doxorubicin in a randomized clinical trial in first-line STS.
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, its improved version of the widely used chemotherapeutic agent doxorubicin. CytRx is also expanding its pipeline of oncology candidates at its laboratory facilities in Freiburg, Germany, through its LADR™ (Linker Activated Drug Release) technology platform, a discovery engine designed to leverage CytRx's expertise in albumin biology and linker technology for the development of a new class of ultra-high potency anti-cancer therapies.
Forward-Looking Statements
This press release contains forward-looking statements. 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 of CytRx's preparation and submission of an NDA for aldoxorubicin for the treatment of STS and FDA acceptance and review of any NDA, the risk that CytRx may be unsuccessful in obtaining FDA approval or, if approval is obtained, in commercializing aldoxorubicin in the United States or elsewhere, risks related to CytRx's need for additional capital or strategic partnerships to fund its ongoing working capital needs and other 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.
Company Contact:
CytRx Corporation David J. Haen Vice President, Business Development and Investor Relations (310) 826-5648, ext. 304 [email protected]
Media Contact: Argot Partners Eliza Schleifstein (973) 361-1546 [email protected]
Investor Relations Contact: Argot Partners Michelle Carroll (212) 600-1902 [email protected]
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The Company plans to submit a rolling NDA under section 505(b)(2) to the FDA for aldoxorubicin as a treatment for STS. The 505(b)(2) pathway is designed for a new drug that contains the same active ingredient as a previously approved drug, also known as a reference drug. For aldoxorubicin, doxorubicin is the reference drug. The NDA submission is not reliant solely on the recently completed Phase 3 clinical trial in STS or overall survival results. Rather, CytRx's completed pharmacokinetic clinical trial, Phase 2b and Phase 3 trials in STS, along with preclinical safety and efficacy studies, will serve as "scientific bridges" between aldoxorubicin and doxorubicin. These studies, along with the published literature of doxorubicin's effectiveness and safety, will form the basis of the NDA filing for aldoxorubicin under the 505(b)(2) regulations.
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"Having worked on aldoxorubicin's regulatory strategy and as a participant in the March FDA meeting, the 505(b)(2) regulatory pathway is the most appropriate for aldoxorubicin in STS," said Scott Wieland, PhD, CytRx's Senior Vice President of Drug Development. "As noted in the FDA meeting, the aldoxorubicin preclinical and clinical studies will support a 505(b)(2) NDA submission, and no new clinical trials were requested by the FDA at the meeting. Additionally, CytRx's previously approved special protocol assessment is no longer applicable."
Aldoxorubicin has received Orphan Drug Designation by the FDA for the treatment of STS. Orphan designation provides several benefits including seven years of market exclusivity after approval, certain R&D related tax credits and protocol assistance by the FDA. European regulators granted aldoxorubicin Orphan Medicinal Product Designation for STS which confers ten years of market exclusivity among other benefits. CytRx plans to discuss with the European Medicines Agency (EMA) a path to filing a Marketing Authorization Application (MAA).
The proposed product label would allow the treatment of soft tissue sarcomas. New data could support future use of aldoxorubicin in neoadjuvant (pre-surgery) settings, as well as a replacement for doxorubicin in chemotherapy combinations. CytRx is also working on a market expansion strategy which would include other indications for aldoxorubicin including combinations with other chemotherapeutics and immunotherapies.
About a 505(b)(2) New Drug Application
A new drug application (NDA) under the Food and Drug Administration's (FDA) section 505(b)(2) is for a new drug containing the same active ingredient as a previously approved drug. According to the publication Regulatory Focus (Reg Focus, Apr. 2010, 8-13.), a drug reviewed under 505(b)(2) represents a modified version of a previously approved product that requires additional clinical and nonclinical studies, other than bioavailability/bioequivalence studies, to demonstrate its safety and efficacy. Such an application differs from a typical NDA in that the sponsor can rely on, at least in part, the FDA's findings of safety and effectiveness for the previously approved reference drug.
About the Phase 2b and Phase 3 Clinical Trials
The global Phase 2b trial involved 123 patients at 31 sites. Patients with advanced soft tissue sarcomas were randomized 2:1 to receive either 350 mg/m2 of aldoxorubicin (83 patients) or 75 mg/m2 of doxorubicin (40 patients) every 3 weeks for up to 6 cycles. The trial was designed to compare aldoxorubicin directly with doxorubicin.
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 350 mg/m2 of aldoxorubicin until disease progression or the investigator's choice of an approved chemotherapeutic regimen, including doxorubicin, ifosfamide, dacarbazine, pazopanib (Votrient®), or gemcitabine plus docetaxel.
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 2017 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 the drug well in excess of 5,000 mg/m2. Aldoxorubicin is the first-ever single agent to show superiority over doxorubicin in a randomized clinical trial in first-line STS.
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, its improved version of the widely used chemotherapeutic agent doxorubicin. CytRx is also expanding its pipeline of oncology candidates at its laboratory facilities in Freiburg, Germany, through its LADR™ (Linker Activated Drug Release) technology platform, a discovery engine designed to leverage CytRx's expertise in albumin biology and linker technology for the development of a new class of ultra-high potency anti-cancer therapies.
Forward-Looking Statements
This press release contains forward-looking statements. 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 of CytRx's preparation and submission of an NDA for aldoxorubicin for the treatment of STS and FDA acceptance and review of any NDA, the risk that CytRx may be unsuccessful in obtaining FDA approval or, if approval is obtained, in commercializing aldoxorubicin in the United States or elsewhere, risks related to CytRx's need for additional capital or strategic partnerships to fund its ongoing working capital needs and other 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.
Company Contact:
CytRx Corporation David J. Haen Vice President, Business Development and Investor Relations (310) 826-5648, ext. 304 [email protected]
Media Contact: Argot Partners Eliza Schleifstein (973) 361-1546 [email protected]
Investor Relations Contact: Argot Partners Michelle Carroll (212) 600-1902 [email protected]
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SOURCE CytRx Corporation
