In studies of human breast cancers transplanted into mice, this new drug stopped tumor growth completely and there were no adverse side effects even when given to the tumor-bearing mice at doses 200 times above its effective dose. The drug, referred to as AFPep because it is a peptide derived from the naturally occurring human pregnancy protein--alpha-fetoprotein (AFP), works differently from any of the drugs currently in use for treatment of breast cancer.
Because peptides are typically destroyed in the stomach by normal digestive processes and thus inadequately absorbed into the blood stream, they are spurned by some pharmaceutical companies in spite of their potential for excellent specificity, high potency, and lack of chemical toxicity. Research by Aegis Therapeutics (San Diego, CA, USA) has shown that peptide-based drugs can be effectively administered orally achieving systemic bioavailabilities of 50%-100% compared to injection when administered using Aegis' patented Intravail formulation technology.
AFPep's oral availability has been demonstrated and it is expected to be administered once daily as a single tablet or capsule. Scientists from Albany Medical College (Albany, NY, USA) and Aegis believe that the combination of these technologies will make it reasonable for pharmaceutical companies to move this unique, nontoxic, and highly promising agent forward into human trials.
Based on preclinical studies, it has been found that AFPep is effective against estrogen receptor-positive breast tumors, which comprise approximately two-thirds of all breast tumors. AFPep also works in combination with tamoxifen against breast cancer growth. It further supplements tamoxifen by reducing the worrisome side effect of uterine growth induced by tamoxifen. Moreover, AFPep suppresses the growth of breast tumors even when they have become resistant to tamoxifen. Development of tamoxifen resistance occurs frequently after prolonged administration of this drug to breast cancer patients, and AFPep would offer an additional agent to women in whom tamoxifen resistance has occurred. The lack of toxicity from AFPep seen to date, and anticipated in human studies, suggests that AFPep has the potential to also be useful as a chemopreventive agent for women who are at high risk for acquiring breast cancer as well as a new treatment agent for shrinkage of existing tumors and prevention of recurrence in patients who have had a tumor removed.
While AFPep has not yet been evaluated in patients, pregnancy provides a compelling clue to its effectiveness. Epidemiologic data show that the full-length AFP protein, which arises in a mother's bloodstream during pregnancy (and from which AFPep was derived), leads to a reduction of breast cancer incidence throughout life. Singleton pregnancies in which AFP levels are found to be higher than normal, and twin pregnancies in which AFP levels are twice those in singleton pregnancies, are seen to afford the greatest breast cancer-risk reduction. It was these observations that led scientists, Dr. James Bennett, Dr. Thomas Andersen, and Dr. Herbert Jacobson from Albany Medical College Albany Medical College to study the underlying process of breast cancer protection by the full-length AFP and to identify the very small portion, representing a mere 1.5% of the full length protein that gives rise to the breast cancer protection effect.
All studies to date support the proof of concept that AFPep captures this pregnancy-based breast cancer protection in a small pill, and will provide significant benefit to women combating this terrible disease. Aegis Therapeutics will begin seeking an appropriate licensee capable of efficiently completing development and securing regulatory approval of this highly promising new drug to make it available to patients in the shortest possible time.
Aegis Therapeutics commercializes its patented drug delivery and drug formulation technologies through product specific licenses. The Intravail technology enables the noninvasive delivery of a wide range of protein, peptide, and nonpeptide macromolecular therapeutics that can currently only be administered by injection with exceptionally high and unmatched bioavailability. The company's ProTek technology provides proprietary, easily manufacturable, aqueous dosage forms that are stable at elevated temperature and that reduce unwanted immunogenicity of many protein and peptide therapeutics.
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Albany Medical College
Aegis Therapeutics
