SANTA MONICA, Calif. and BOSTON, Nov. 18 /PRNewswire-FirstCall/ -- American BioScience, Inc. presented data today at the joint American Association of Cancer Research/National Cancer Institute and EORTC (European Organisation for Research and Treatment of Cancer) Symposium in Boston highlighting research on the delivery of active pharmaceutical compounds via a novel, nanoparticle protein-engineered technology platform.
nab(TM) (nanoparticle albumin-bound) technology, for the first time, combines a physiologically interactive human protein, albumin, with an active pharmaceutical agent, resulting in compounds which are free of toxicities associated with the use of solvent-based formulations. The compound closest to commercialization is nab(TM) paclitaxel, for which positive results in Phase II and III trials in patients with metastatic breast cancer were presented. These findings supplemented a recent presentation about this compound, called ABRAXANE(TM), at a late-breaking session at the annual Chemotherapy Foundation Symposium in New York City last week.
ABRAXANE(TM) is a solvent-free, next generation taxane that delivers paclitaxel via an albumin-bound nanoparticle. The study of ABRAXANE in the clinical setting allows for the first time the ability to examine the toxic effects conferred by the solvent itself versus the toxicity associated with the active agent, paclitaxel, alone. American BioScience (ABI) reported data from clinical studies demonstrating that the absence of the toxic solvent Cremophor(R) allows ABRAXANE(TM) (260mg/m2) to be administered by a 30-minute infusion time versus 3 hours with Taxol(R) (175mg/m2), without severe hypersensitivity reactions among patients not given the standard taxane premedications, with a lower incidence of neutropenia than seen with Taxol, and with a rapid resolution of paclitaxel-induced peripheral neuropathy. Higher doses of paclitaxel were well tolerated by study subjects in the absence of the solvent. Consistent with these higher doses of paclitaxel, Grade 3 neuropathy occurred more frequently in patients receiving ABRAXANE, but, with the rapid resolution, this event was easily managed. ABI believes that this study provides important clinical evidence on the impact of Cremophor(R) on both on the degree of bone marrow suppression as well as on the time for recovery after solvent-induced neuropathy. The Phase III results will be submitted to the U.S. FDA in the near future.
ABI has licensed the North American manufacturing and marketing rights for ABRAXANE(TM) to American Pharmaceutical Partners, Inc. (APP), has filed two of the three required sections of the NDA submission to the FDA and will disclose detailed results of its Phase III randomized, controlled, 460-patient study on December 5 at 7:45 p.m. during the late-breaker session at the San Antonio Breast Cancer Symposium.
"Although ABRAXANE is an investigational agent not yet approved by the FDA, we're encouraged by the clinical results we've seen thus far, and are further excited by the potential of nab technology to improve treatment options for breast cancer patients," said Michael J. Hawkins, M.D., Chief Medical Officer of ABI.
Solvent and Detergent-Free Nanoparticle Albumin-Bound (nab(TM)) Technology
ABI's Nanoparticle Albumin-Bound (nab(TM)) technology integrates biocompatible human proteins with active pharmaceutical agents to create the amorphous, nanoparticle form of the drug and allows the administration of these compounds without the use of toxic solvents or detergents. "The nab technology is applicable to a wide variety of insoluble drugs over a range of therapeutic areas," said Neil Desai, Ph.D., Vice President, R&D at ABI.
"While the application in oncology is the furthest along, we are also developing the technology for potential use in cardiology where nab paclitaxel has been shown to significantly reduce coronary artery restenosis in animal models after only a single injection," continued Desai. "We have initiated clinical trials in patients with coronary artery disease with single dose therapy following balloon angioplasty and stenting and are hopeful that our clinical findings will corroborate the positive preclinical data."
In addition to the use of the nab(TM) technology for paclitaxel and other novel anticancer compounds, other potential therapeutic areas of application may include immunosuppression, for prevention of transplant rejection with drugs like rapamycin where no injectable form exists and cyclosporine, the i.v. form of which must be administered with Cremophor due to insolubility. These applications have all been presented earlier in the year at various scientific conferences including the American Society of Anesthesiology meeting recently held in San Francisco (first albumin-bound nanoparticle propofol to the innovator drug Diprivan(R)) and the American Association of Clinical Research meeting in Washington, DC (pulmonary delivery of nab(TM) paclitaxel).
ABRAXANE(TM): nab(TM) Paclitaxel
Nanoparticle albumin-bound (nab(TM)) technology has been shown to enable the delivery of higher concentrations of paclitaxel to tumor tissues, with lower concentrations of the drug in normal, healthy tissue. ABRAXANE (previously known as ABI-007) is made of tiny particles of paclitaxel and human albumin protein. The nanoparticles are about 1/100th the size of a red blood cell.
Preclinical models had shown that there is increased intratumoral paclitaxel concentration, lower drug concentration in normal, healthy tissues, and greater antitumor activity with ABRAXANE versus Cremophor(R)-based paclitaxel. The mechanisms by which nab paclitaxel has been shown in these preclinical models to deliver selectively higher tumor concentrations of paclitaxel are currently being studied. ABI believes a potential mechanism for this effect of higher intratumoral concentrations may be the interplay of the intrinsic physiological activity of albumin, an enhanced permeation and retention (EPR) effect of nanoparticles, and the abnormal leaky vasculature of the cancer cells.
Historically, taxanes have been solubilized in toxic solvents, either Cremophor(R)-EL (Taxol(R)) or Tween(R) (Taxotere(R)). Reports in scientific literature confirm the association of Cremophor to numerous toxic effects including axonal swelling, demyelination, myelosuppression and neutropenia (dangerously low levels of white blood cells). Cremophor has also been reported to interfere with drug activity by entrapping molecules of paclitaxel in molecular clumps called micelles, thereby decreasing the bioavailability of paclitaxel for antitumor effect.
"Despite many attempts over the past decade to avoid the use Cremophor, it was viewed as the only available method enabling administration of paclitaxel to patients," said Michael Hawkins, M.D. "Today, however, it is apparent that Cremophor is not an innocent bystander and may change the nature of the toxicities of drugs formulated with this solvent. Specifically, our trials suggest that both neutropenia and prolonged recovery of neuropathy may be a Cremophor-associated toxicity. We are hopeful that the innovative nab technology platform will usher in a new era for cancer treatments."
About the Companies
American BioScience, Inc. is a privately held biotechnology company focused on the discovery, development and delivery of next generation therapeutic entities for the treatment of life-threatening diseases.
American Pharmaceutical Partners, Inc. (APP), a majority owned subsidiary of American BioScience, Inc., is a specialty drug company that develops, manufactures and markets injectable pharmaceutical products, focusing on oncology, anti-infectives and critical care. APP has acquired the exclusive North American rights to manufacture and market ABRAXANE(TM), a proprietary nanoparticle injectable oncology product that has completed Phase III clinical trials for metastatic breast cancer and for which the FDA has granted "Fast Track" designation. ABRAXIS Oncology is a newly created division of APP that will be responsible for the commercialization of ABRAXANE(TM) in the United States. The company believes that it has established the only commercial scale protein-engineered nanoparticle manufacturing capability in the United States. For more information, visit APP's website at http://www.appdrugs.com/ .
Statements contained in this press release, which are not historical facts, are forward-looking statements, as the term is defined in the Private Securities Litigation Reform Act of 1995. Such forward-looking statements, whether expressed or implied, are subject to risks and uncertainties which can cause actual results to differ materially from those currently anticipated, due to a number of factors, which include, but are not limited to, the impact of pharmaceutical industry regulation, the difficulty in predicting the timing or outcome of product development efforts and FDA or other regulatory approvals or actions, the impact of competitive products and pricing, the availability and pricing of ingredients used in the manufacture of pharmaceutical products, the ability to successfully manufacture products in a time-sensitive and cost effective manner, the acceptance and demand of new pharmaceutical products, the impact of patents and other proprietary rights held by competitors and other third parties, actual results achieved in Phase III and further Phase II trials for ABRAXANE which may or may not be consistent with results achieved in Phase I and Phase II trials, the timing and completion of the ABRAXANE trials, and other risk factors discussed in American Pharmaceutical Partners' Form 10-K and other documents filed by the Company with the Securities and Exchange Commission from time to time. These forward-looking statements represent the Company's judgment as of the date of this press release. The Company disclaims any intent or obligation to update these forward-looking statements.
TAXOL is a registered trademark of Bristol-Myers Squibb Company.
TAXOTERE is a registered trademark of Aventis.
American BioScience Inc.