Lots of questions about the trial design (not to mention the dubious founder), but these results on the surface look good - should make for an interesting battle in the context of a big short position:
Press Release Source: American Pharmaceutical Partners, Inc.
Detailed Positive ABRAXANE(TM) Phase III Data Released at San Antonio Breast Cancer Symposium: Patients With Metastatic Breast Cancer Treated With ABRAXANE(TM) Achieve Almost Double the Tumor Response Rate and Longer Time to Tumor Progression Compared With TAXOL(R)
Friday December 5, 4:30 pm ET
SCHAUMBURG, Ill. and SANTA MONICA, Calif., Dec. 5 /PRNewswire/ -- American Pharmaceutical Partners, Inc. (Nasdaq: APPX - News; APP) and ABRAXIS Oncology, the proprietary drug division of APP, today announced positive results of the randomized, controlled Phase III clinical trial in patients with metastatic breast cancer comparing the investigational product ABRAXANE(TM) (formerly ABI-007) to the Cremophor® solvent-based TAXOL®. A detailed analysis of the study was presented by Joyce O'Shaughnessy, M.D., Co-Director, Breast Cancer Research and Director, Breast Cancer Prevention at Baylor-Charles A. Sammons Cancer Center, US Oncology in Dallas, Texas, and William Gradishar, M.D., FACP, Associate Professor of Medicine, Division of Hematology and Medical Oncology and Co-Director, Lynn Sage Breast Cancer Program at Northwestern University in Evanston, Illinois, to an audience of oncologists at a late-breaking session and Scientific Symposium at the San Antonio Breast Cancer Symposium held in San Antonio, Texas last Friday evening.
Patients with metastatic breast cancer receiving the solvent-free nanoparticle paclitaxel, ABRAXANE(TM) (n=229 patients) achieved almost a doubling of the tumor response rate when compared to those patients receiving Bristol-Myers Squibb's TAXOL® (n=225). "The robustness of the data is underscored by the fact that statistically superior response rates with ABRAXANE(TM) compared to TAXOL were noted regardless of whether the data was assessed by the blinded, independent radiology review or the investigator assessment," said Joyce O'Shaughnessy, M.D.
Although the ABRAXANE(TM) data and labeling remain subject to FDA review, the Phase III study demonstrated potentially important advantages over TAXOL as a treatment for metastatic breast cancer patients, based on: higher response rates; longer time to tumor progression; absence of severe hypersensitivity reactions without the need for premedication; less neutropenia despite a higher dose infused over a shorter period of 30 minutes; and, a rapid recovery from sensory neuropathy compared with TAXOL, albeit with a somewhat higher incidence consistent with the higher dosage administered.
Specifically, the results reported were as follows:
-- A significantly higher Overall Tumor Response Rate (ORR) was noted in
patients receiving ABRAXANE(TM) (33%) versus TAXOL(R) (19%),
(p=0.001). Similarly, analysis of the Target Lesion Response Rate
(TLRR) showed significantly higher anti-tumor activity (p<0.001) with
ABRAXANE(TM);
-- In patients receiving chemotherapy for metastatic breast cancer for
the first time (first-line patients), a significantly higher tumor
response was also noted, with 42% of ABRAXANE(TM) patients (n=97)
responding to the therapy compared with a 27% response rate in
patients (n=89) receiving TAXOL (p=0.029);
-- Similarly, the response rates with ABRAXANE(TM) were higher, and
statistically significant, when analyzed in those patients who had
failed prior chemotherapy, and in patients with poor prognostic
indicators such as in those with liver metastases (26%, n=92 vs. 13%,
n=97) and lung metastases (43%, n=74 vs. 25%, n=79);
-- A longer time to tumor progression was noted in patients receiving
ABRAXANE(TM), with a median of 21.9 weeks versus a median progression
time of 16.1 weeks after TAXOL, (p=0.030);
-- 98% of cycles of ABRAXANE(TM) were administered without steroid
premedication and no evidence of severe hypersensitivity reactions
were noted in any of these patients thus confirming the ability to
safely administer this solvent-free paclitaxel without the need for
premedication. In contrast, 95% of the doses of TAXOL were
administered with steroids and anti-histamines, and still these
patients showed a significantly higher incidence of flushing than
those patients receiving ABRAXANE without pre-medication;
-- Both treatments were well tolerated with 98% of patients receiving the
planned dose on both arms; the mean total paclitaxel dose delivered
with ABRAXANE(TM) was 1459mg per patient per m2 and 909mg per patient
per m2 with TAXOL;
-- Consistent with this higher dose of paclitaxel delivered with
ABRAXANE(TM), the incidence of Grade 3 sensory neuropathy was 10%
versus 2% in the patients receiving TAXOL (p<0.001). The Grade 3
sensory neuropathy resolved rapidly in the ABRAXANE(TM) patients
within a median of 22 days and was thus easily managed. In contrast,
and consistent with current clinical experience, recovery of the
neuropathy after TAXOL administration was significantly prolonged with
a median of 79 days (p=0.028). This finding suggests that it is
possible, consistent with preclinical studies in the literature, that
the Cremophor component of TAXOL may be responsible for structural
damage (demyelination) to the nerve fibres resulting in prolonged
neuropathy, while neuropathy due to paclitaxel alone is transient with
rapid resolution. There were no reports of Grade 4 sensory neuropathy
or severe motor neuropathy in either arm;
-- Despite the higher dose of paclitaxel delivered, there was
significantly less Grade 4 neutropenia with ABRAXANE(TM) (9%) compared
to TAXOL (22%), providing the first clinical evidence that Cremophor
may contribute to bone marrow damage and loss of white blood cells;
-- Fluid retention was infrequent in both arms and there were no septic
deaths in the study.
"It is clear that the solvent Cremophor is not an innocent bystander," said William Gradishar, M.D., the Principal Investigator of the study. "The findings of this Phase III clinical trial provide the first clinical evidence that Cremophor may be responsible not only for the severe hypersensitvity reactions that necessitate steroid pre-medication, but that the toxic effects of this solvent on patients may be more far-reaching than previously recognized. Data from this trial suggest that Cremophor itself may be responsible for the loss of protective white blood cells, by suppressing the bone marrow, and, furthermore, that the solvent-induced damage to nerve fibres, rather than paclitaxel itself, may account for the prolonged recovery of peripheral neuropathy noted with TAXOL."
"We are extremely pleased that the increase in anti-tumor activity we had seen with ABRAXANE(TM) in preclinical studies was confirmed in this Phase III trial, and further translated into an increased time to tumor progression in patients with metastatic breast cancer," said Michael J. Hawkins, M.D., Chief Medical Officer at American BioScience, Inc., the company responsible for developing ABRAXANE(TM).
"Our preclinical data indicated that higher intratumor concentrations of paclitaxel were achieved following administration of ABRAXANE(TM), compared to equal doses of TAXOL. This effect, coupled with our ability to increase the dose of paclitaxel administered, predicted that ABRAXANE(TM) would have more anti-tumor activity than TAXOL. This is now supported by the results of our randomized Phase III study. We will now expeditiously complete filing of the NDA, which has been granted fast-track designation."
Protosphere(TM) Nanoparticle Albumin-Bound (nab) Technology - The Foundation Technology for ABRAXANE(TM)
American BioScience's Protosphere Nanoparticle Albumin-Bound (nab) technology integrates biocompatible proteins with drugs to create the amorphous, nanoparticle form of the drug. These nanoparticles act as biologic nanotransporters for hydrophobic drugs such as paclitaxel, which may result in increased intracellular availability of the chemotherapeutic agent at the tumor site. At the San Antonio conference, American BioScience presented, for the first time, data that provides evidence of a novel receptor-mediated albumin-bound transporter mechanism for paclitaxel believed to play a role in increased penetration of the active drug into tumor tissue, by a mechanism of "transcytosis." |
