Our product candidate, eflornithine, is a novel cytostatic (growth inhibiting) agent, which we are developing for the potential treatment of patients with anaplastic astrocytoma (AA).
Eflornithine, also known as α-diflurormethylornithine (DFMO) selectively targets and irreversibly inhibits ornithine decarboxylase (ODC), an enzyme essential for polyamine synthesis, and DNA and RNA function. Unlike multi-targeted tyrosine kinase inhibitors on the market or in development today, eflornithine targets only one enzyme, ODC.
Eflornithine injection was approved by the FDA in 1990 for the treatment of African trypanosomiasis (sleeping sickness), but it was never made commercially available in the U.S. In 2000, the FDA approved a topical eflornithine cream for the reduction of unwanted facial hair in women.
Eflornithine oral solution is an investigational product that has not been proven to be safe and effective in treating patients with recurrent anaplastic astrocytoma (rAA). Eflornithine oral solution may only be administered to patients who participate in the STELLAR trial. Eflornithine oral solution is not licensed for the treatment of rAA in the United States or any other country.
In animal studies, eflornithine has been shown to inhibit the growth of malignant tumors, including intra cerebral high-grade gliomas. Eflornithine administration has also been shown to potentiate the anti-tumor activity of other chemotherapy agents.
In controlled, randomized, and single-arm clinical trials enrolling patients with newly diagnosed anaplastic astrocytoma (AA) or rAA,1 2 3 4 treatment with eflornithine oral solution increased survival. In these clinical trials, the primary and reversible side effects of eflornithine use in a small percentage of patients were diarrhea and hearing loss.
In 2014, Orbus Therapeutics received breakthrough therapy designation from the FDA for eflornithine for the treatment of patients with anaplastic glioma. A new drug may be designated as a breakthrough therapy by the FDA if it is intended to treat a serious or life-threatening disease and preliminary evidence suggests it provides substantial improvement over existing therapies.
1. Shantz LM and Levin VA. Regulation of ornithine decarboxylase during oncogenic transformation: mechanisms and therapeutic potential. Amino Acids. 2007;33(2):213-223.
2. Levin VA, Prados MD, Yung WK, Gleason MJ, Ictech S, Malec M. Treatment of recurrent gliomas with eflornithine. J Natl Cancer Inst. 1992;84(18):1432-1437.
3. Levin VA, Hess KR, Choucair A, Flynn PJ, Jaeckle KA, Kyritsis AP, Yung WK, PradosMD, Bruner JM, Ictech S, Gleason MJ, Kim HW. Phase III randomized study of post radiotherapy chemotherapy with combination alpha-difluromethylornithine-PCV versus PCV for anaplastic gliomas. Clin Cancer Res. 2003;9(3):981-990
4. Levin VA, Ictech SE, Hess KR. Clinical importance of eflornithine (α-difluoromethylornithine) for the treatment of malignant gliomas. CNS Oncology. Published Online: 30 Jan 2018. https://www.futuremedicine.com/doi/10.2217/cns-2017-0031
Anaplastic Astrocytoma (or AA) is a rare form of brain cancer. AA develops from astrocytes, a type of cell that normally wraps and protects nerves in the brain and spinal cord. The specific cause of AA is not known. Most AAs grow slowly over time, but some grow quickly. Some AAs transform to become a more aggressive type of tumor called glioblastoma.
AA is most common in adults aged 30 to 50 years, although it can affect all ages. A detailed list of symptoms, complete physical exam, and imaging tests, such as an MRI or a CT scan of the brain, are part of the medical evaluation. The diagnosis of AA maybe confirmed by collecting tumor tissue during surgery for inspection under a microscope and for specialized genetic tests.
Surgery, radiation therapy, and chemotherapy can be used alone or together to treat AA. Treatment usually begins with surgery to reduce the size of the tumor. Surgery is usually followed by radiation therapy and chemotherapy with temozolomide (the generic drug name for Temodar®). The type and sequence of therapies may be different for each patient, depending on each unique situation.
When the tumor starts to grow after treatment, AA is called recurrent anaplastic astrocytoma (or rAA). Currently, there are very few therapies for patients with rAA or AA that has progressed (grown larger or changed in appearance).
Source: National Organization of Rare Disorders website