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American Pharmaceutical Partners Presents Data on High Dose Weekly ABRAXANE(TM) in Taxane-Refractory Metastatic Breast Cancer Patients

Posted on: Monday, 13 December 2004, 15:00 CST

SCHAUMBURG, Ill., Dec. 13 /PRNewswire-FirstCall/ -- American Pharmaceutical Partners, Inc. announced positive results from a recent Phase II clinical study indicating that weekly administration of ABRAXANE(TM) (nanoparticle albumin-bound paclitaxel) resulted in long-term disease control in patients with metastatic breast cancer whose disease had progressed while being treated with Taxol or Taxotere (that is, patients who are taxane-refractory). In addition, American Bioscience, Inc. (ABI) presented two posters detailing the transport mechanisms of the paclitaxel albumin-bound nanoparticle protein. These findings were presented at the 27th Annual San Antonio Breast Cancer Symposium (SABCS) in San Antonio, TX.

The three posters presented were entitled:

1) Weekly Nanoparticle Albumin Paclitaxel (ABRAXANE(TM)) Results in

Long-term Disease Control in Patients with Taxane-refractory Metastatic

Breast Cancer

2) Increased Endothelial Transcytosis of Nanoparticle Albumin-bound

Paclitaxel (ABI-007) by gp60-receptors: A Pathway Inhibited by Taxol(R)

3) SPARC Expression in Breast Tumors May Correlate to Increase Tumor

Distribution of Nanoparticle Albumin-bound Paclitaxel (ABI-007) vs.

Taxol(R)

ABRAXANE represents the first biologically interactive composition that exploits the receptor-mediated (gp60) pathway found to be integral to achieving high intracellular tumor concentrations of the active ingredient -- paclitaxel. The Phase II study, which was sponsored by American Bioscience, included 75 patients with taxane-refractory metastatic breast cancer. ABRAXANE was administered weekly via a 30-minute infusion at 125 mg/m2 without steroid/antihistamine premedication or G-CSF prophylaxis. Patients received three weekly doses followed by one week of rest, repeated every 28 days.

"This Phase II study reinforces previous findings that demonstrated activity with ABRAXANE in metastatic breast cancer patients where Taxol or Taxotere had failed," said Patrick Soon-Shiong, M.D., Executive Chairman of American Pharmaceutical Partners. "By harnessing the tumor's own mechanism for nourishment and essentially tricking it to feed, via the gp60 pathway, on nanoparticle albumin paclitaxel, more active drug may be delivered to the tumor site with the least amount of damage to normal tissues. Unlike Taxol or Taxotere, which contain detergents that may inhibit tumor uptake, the novel mechanism of action of the albumin-bound nanoparticle paclitaxel may result in improved outcomes, especially in this difficult-to-treat patient population."

"We are very excited about the 125 mg/m2 weekly data in taxane-refractory patients," stated Michael Hawkins, M.D., Chief Medical Officer, of American Bioscience. "Specifically, the data showed that despite this high weekly dose in this highly pre-treated and prior taxane-exposed patient population, only 3 of 75 patients (4%) had to discontinue ABRAXANE due to peripheral neuropathy. Furthermore, of those who experienced Grade 3 peripheral neuropathy, 80% were typically able to resume treatment after a delay of only 1 or 2 weeks and continued to receive ABRAXANE at a reduced dose for an average of 4 additional months. This rapid improvement is consistent with our observation from the Phase III trial-namely that the peripheral neuropathy induced by paclitaxel alone (i.e., without Cremophor) improves rapidly. These ABRAXANE clinical trial experiences provide the first clinical opportunity to evaluate the effects of the chemotherapeutic agent itself, paclitaxel, from the effects from those of solvents. Based upon both the Phase II and III experience, the data now suggests that the peripheral neuropathy from ABRAXANE is not comparable to the peripheral neuropathy from Taxol or Taxotere with respect to duration and impact on the patient."

With regard to the clinical experience of peripheral neuropathy following Taxol or Taxotere, Abraxis Oncology recently completed a survey of 200 oncologists who were asked how long they thought the peripheral neuropathy induced by Taxol took to improve and/or resolve: 25% reported "7-12 months" and another 23% reported "never resolved"; for Taxotere, the respective percentages were 29% and 7%. These data are consistent with the statements in the Taxotere and Taxol package inserts.

Analysis of the Phase II data demonstrates ABRAXANE to be active in this poor-prognosis patient population (87% visceral (lung and liver) disease, 69% >3 metastatic sites, 88% tumor growth while on taxanes), of taxane-refractory patients with metastatic breast cancer. Observations included a 44% disease control in Taxotere-refractory patients and 39% disease control in Taxol-refractory patients. Of those patients whose disease progressed while on Taxotere alone in the metastatic setting (n=27) a 19% response rate was noted after receiving weekly ABRAXANE. Of those patients whose disease progressed while on Taxol alone in the metastatic setting (n=23) a 13% response rate was noted after receiving weekly ABRAXANE.

ABRAXANE was found to be well tolerated when administered weekly over 30 minutes without steroids or G-CSF prophylaxis: Grade 4 neutropenia = 3% (without G-CSF); Grade 4 anemia = 1%; No severe hypersensitivity reactions (despite absence of premedication). In this heavily pretreated patient population, 75% of patients were treated at the full high dose of 125 mg/m2 weekly ABRAXANE, with no dose reductions due to toxicities/adverse events. Of the patients who developed grade 3 sensory neuropathy, 77% were able to restart ABRAXANE at a reduced dose (75-100 mg/m2) and received a mean of 12.2 (range, 1-28) additional doses of ABRAXANE.

"It was remarkable to note that of these patients who resumed ABRAXANE, 80% (8 of 10) were able to restart the drug within 14 days after improvement of neuropathy to Grade 1 or 2," said Joyce O'Shaughnessy, M.D., Co-Chair, Breast Cancer Research, Baylor-Sammons Cancer Center, US Oncology, Dallas, TX, and principal author of this Phase II study. "These results support the observations in the pivotal Phase III trial of 260 mg/m2 ABRAXANE administered every 3 weeks, in which rapid improvement of neuropathy (median of 22 days) was also noted. Taken together these two clinical trials suggest when paclitaxel is given alone, the neuropathy which occurs, appears to be short-lived and is easily managed," she said.

In 2 separate presentations American Bioscience presented posters detailing the transport mechanisms of ABRAXANE. The presentations detailed how ABRAXANE utilizes the gp60 receptor based pathway on the microvessel endothelial cells to transport the albumin-paclitaxel complex out of the blood vessel and into the tumor interstitium, and showed that Taxol was not transported by this mechanism. Furthermore, ABI scientists showed that an albumin-binding protein, SPARC, was over-expressed in breast tumors and may play a role in the increased intra-tumoral accumulation of ABRAXANE. The proposed mechanism suggested that once in the tumor interstitium, the albumin-paclitaxel complex would bind to SPARC that was present on the tumor cell surface and be rapidly internalized into the tumor cell by a non-lysosomal mechanism.

Data was also presented indicating that the surfactants/solvents commonly used in current taxaneformulations such as Cremophor, Tween 80 and TPGS, strongly inhibit the binding of paclitaxel to albumin, thereby limiting transendothelial transport. Additional data presented showed a statistically improved efficacy of ABRAXANE over Taxotere in the MX-1 mammary breast carcinoma xenograft at equal dose.

About the Companies

ABI and APP are strategic partners in the development, manufacture and marketing of ABRAXANE. ABI is responsible for the clinical development and registration of ABRAXANE. APP has licensed the North American manufacturing and marketing rights for ABRAXANE.

American Bioscience, Inc. (ABI) is a privately held biotechnology company focused on the discovery, development and delivery of next-generation therapeutic moieties including biologically active molecules already existing within the human biological system, for the treatment of life-threatening diseases. American Pharmaceutical Partners, Inc. is a majority owned subsidiary of American Bioscience, Inc.

About American Pharmaceutical Partners

American Pharmaceutical Partners, Inc. is a specialty drug company that develops, manufactures and markets injectable pharmaceutical products, focusing on the oncology, anti-infective and critical care markets. 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 with the NDA currently under review by the FDA. 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 including the approval of ABRAXANE(TM), 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 further Phase II and III trials for ABRAXANE(TM) may or may not be consistent with results achieved to date, the timing and completion of the ABRAXANE(TM) filing, the fact that the FDA has not reviewed the Phase III data and may not grant approval on the basis of such data, and other risk factors discussed in the Company's 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 Pharmaceutical Partners, Inc.

CONTACT: Nicole Williams, Executive Vice President & CFO of AmericanPharmaceutical Partners, Inc., +1-847-969-2700; or Rob Whetstone or RobertJaffe, both of PondelWilkinson Inc., +1-310-279-5963, for AmericanPharmaceutical Partners, Inc.

Web site: http://www.appdrugs.com/

Source: PRNewswire-FirstCall

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