The US Food and Drug Administration (FDA) has granted multiple Orphan Drug Designations for the CytRx Corporation's lead drug candidate, aldoxorubicin, in three indications: glioblastoma multiforme (GBM), small cell lung cancer (SCLC) and ovarian cancer.  Aldoxorubicin is CytRx's modified version of the widely-used chemotherapeutic agent, doxorubicin.

"The FDA's decision to grant Orphan Drug designation for aldoxorubicin in these three new indications is a key milestone for the aldoxorubicin clinical development programme and a clear reflection of the high unmet medical need for new treatments in these cancer types," said Steven A Kriegsman, CytRx president and chief executive officer.  "These designations are also a testament to the team's regulatory and development expertise and part of our core strategy to bring aldoxorubicin to patients worldwide as rapidly as possible.  We look forward to reporting top-line results from both our phase 2 GBM trial and our phase 2 Kaposi's sarcoma trial in the first half of 2015."

In the US, under the Orphan Drug Act, the FDA's Office of Orphan Products Development (OOPD) grants orphan drug status to a drug intended to treat a rare disease or condition, which is generally a disease that affects fewer than 200,000 individuals in the country.  Upon approval, if received, the designation provides aldoxorubicin with certain benefits, including seven years of US market exclusivity in the specified indications if the sponsor complies with certain FDA requirements.  Additional incentives for the sponsor include tax credits related to qualified clinical trial expenses and a possible exemption from FDA application fees.

Aldoxorubicin is currently being studied in a pivotal global phase 3 clinical trial evaluating the efficacy and safety of aldoxorubicin as a second-line treatment for patients with soft tissue sarcoma (STS) under a Special Protocol Assessment with the FDA.  CytRx is also evaluating aldoxorubicin in two phase 2 clinical trials, one in patients with late-stage GBM and the other in HIV-related Kaposi's sarcoma. The company expects to start a global phase 2b trial in patients with relapsed small cell lung cancer this month and is undertaking a phase 1b combination study of aldoxorubicin plus gemcitabine as a potential precursor to a trial in relapsed ovarian cancer.

An estimated 1.6 million new cases of lung cancer are diagnosed worldwide each year.  In the Western world, approximately 13-15% of cases are SCLC, a deadly form of lung cancer associated with tobacco use.  The five year survival rate is less than 7%, in part because an estimated 70% of patients have extensive disease at diagnosis.  According to the National Cancer Institute, more than 30,000 new cases will be diagnosed in the USA in 2014.  The estimated 2014 SCLC incidences for Europe and Asia are over 58,000 and 136,000, respectively.  

Glioblastoma is the most common and most malignant brain tumour in adults and afflicts more than 12,000 new patients in the US annually. Despite surgical resection, radiotherapy and chemotherapy, the median survival after diagnosis is approximately 12 to 14 months. Limited efficacy of chemotherapeutic agents has been attributed to several contributing factors including insufficient drug delivery to the tumour site through the blood-brain barrier.

Ovarian cancer is the ninth most common cancer and accounts for 3% of all cancers in women. Ovarian cancer ranks as the fifth most frequent cause of death by cancer among women, accounting for more deaths than any other cancer of the female reproductive system. One out of every 71 women is at risk of developing ovarian cancer, and one out of every 95 women dies from ovarian cancer.  In the US alone, there will be approximately 22,000 new cases of ovarian cancer diagnosed in 2014.  Worldwide, ovarian cancer is diagnosed annually in nearly 250,000 women, and is responsible for 140,000 deaths each year.

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 tumours concentrate albumin, thus increasing the delivery of the linker molecule with the attached doxorubicin to tumour sites. In the acidic environment of the tumour, but not the neutral environment of healthy tissues, doxorubicin is released. This allows for greater doses (3 ½ 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 2,000 mg/m2.

CytRx Corporation is a biopharmaceutical research and development company specializing in oncology.