INVESTORS & MEDIA
News Release
Sanofi-aventis and Regeneron Announce Results from Phase 2 Study with Aflibercept (VEGF Trap) in Advanced Ovarian Cancer Patients with Recurrent Symptomatic Malignant Ascites
Mean time to first repeat paracentesis following a baseline procedure was 55 days with aflibercept as compared to 23 days for patients receiving placebo (p=0.0019). Time to first repeat paracentesis was defined as the number of days between study randomization and the first post-randomization paracentesis or, in cases where there was no repeat paracentesis, study withdrawal, death, or six months from randomization.
There was a similar incidence of deaths in both treatment groups (no statistically significant difference; hazard ratio 1.02). In this late-stage patient population with advanced ovarian cancer who were heavily pre-treated (median of four prior courses of chemotherapy), four fatal events were assessed by the investigators as aflibercept treatment related, including one case each of intestinal perforation, dyspnea, pneumonia, and cause unknown.
The types and frequencies of adverse events reported with aflibercept in this study were generally consistent with those reported in clinical studies with other anti-VEGF therapies in advanced ovarian cancer patients.
"The results of this Phase 2, placebo-controlled study demonstrate that
aflibercept is a clinically active agent in patients with advanced
ovarian cancer with symptomatic malignant ascites. However, given the
small number of patients enrolled in this study and the fragile health
status of these advanced ovarian cancer patients, who had a median
survival of only about three to four months, it is difficult to
definitively assess the overall clinical benefit that might be derived
from treatment in the real-world clinical practice setting,” stated
About the Phase 2 Study
This double-blind, placebo-controlled, multi-center Phase 2 trial enrolled 55 patients with symptomatic malignant ascites, related to advanced ovarian cancer, who had failed a prior platinum-based chemotherapy regimen and who had also received chemotherapy treatment with either liposomal doxorubicin or topotecan. All patients had to have undergone between one and four prior paracenteses in the month prior to randomization in addition to a baseline procedure. Twenty-nine patients were randomized to receive aflibercept administered intravenously as 4 milligrams per kilogram of patient body weight (mg/kg) and 26 patients were randomized to placebo. Patients were dosed every two weeks. In this study the double-blind treatment period was defined as the earliest of the date of death, withdrawal from the study, six months, or entry into open-label treatment. All patients were offered the opportunity to receive open-label aflibercept after 60 days of double-blind treatment provided that at least one post-randomization paracentesis had occurred.
There was a statistically significant 2.4-fold lengthening of time to first repeat paracentesis with aflibercept as compared to placebo. Pre-specified secondary endpoint results were consistent with this primary endpoint finding. The frequency of paracentesis over the first 60 days of the study was reduced, on average, by nearly 50 percent in patients receiving aflibercept versus those receiving placebo (p=0.0035). Patient-reported symptoms of ascites, including abdominal discomfort, pain, and bloating, as well as patients’ ability to move, were recorded daily from the time of randomization to the time of first repeat paracentesis. Among those patients for whom baseline and follow-up data were available, the cumulative symptoms score results demonstrated a statistically significant improvement in symptoms with aflibercept as compared to placebo.
Severe (Grade 3 or 4) adverse events (AEs) that occurred at a frequency of at least 10 percent in patients who received either aflibercept or placebo were as follows (aflibercept vs. placebo): fatigue or asthenia (13% vs. 44%), dyspnea (20% vs. 8%), peripheral edema (7% vs. 12%), anorexia (7% vs. 12%), dehydration (10% vs. 12%), and hypocalcemia (10% vs. 0%). Grade 3/4 hypertension and proteinuria occurred at a frequency of 7 percent in the aflibercept group. There were four fatal gastrointestinal events reported in the double-blind period of the study. The events include three intestinal perforations in the aflibercept group (10 percent of aflibercept safety population; only one of which was assessed by the investigators as treatment related) and one intestinal fistula in the placebo group (4 percent of placebo safety population).
The results reported are from a preliminary analysis. A full analysis of the final study results will be presented at a future medical meeting.
About Symptomatic Malignant Ascites
Symptomatic malignant ascites is an abnormal build-up of fluid in the abdominal cavity in patients with advanced cancer. In ovarian cancer patients, malignancies can spread throughout the abdominal cavity. In these patients the accumulation of fluid is the result of increased vascular permeability and blockage of the lymphatic channels that regulate the volume of intraperitoneal fluid. Ascites can cause pain, discomfort, limitations on mobility, interference with normal breathing, and other symptoms that impact patients’ ability to function. Paracentesis, a common surgical procedure used to remove excess fluid from the abdominal cavity in patients with advanced ovarian cancer, can provide immediate symptomatic relief, but its effects are generally short-lived; on average, several liters of fluid need to be withdrawn as often as every one to two weeks. Paracentesis can be associated with hypotension, peritonitis, pulmonary embolism, visceral/vascular injury, and malnourishment.
About Aflibercept (VEGF Trap)
Aflibercept is an antiangiogenesis inhibitor with a unique mechanism of action. This fusion protein binds all forms of Vascular Endothelial Growth Factor-A (VEGF-A), VEGF-B, and placental growth factor (PIGF), another angiogenic growth factor that appears to play a role in tumor angiogenesis and inflammation. Aflibercept has been shown to bind VEGF-A, VEGF-B, and PlGF with higher affinity than their natural receptors.
About the Phase 3
Aflibercept is currently in Phase 3 clinical development in combination with standard chemotherapy in the following indications:
- VELOUR study: 2nd-line metastatic colorectal cancer in combination with fluorouracil, leucovorin, and irinotecan (FOLFIRI)
- VITAL study: 2nd-line non-small cell lung cancer in combination with docetaxel
- VANILLA study: 1st-line pancreatic cancer in combination with gemcitabine
-
VENICE study: 1st-line hormone-refractory metastatic prostate cancer in combination with docetaxel and prednisone
Each study is over 60 percent enrolled. Initial data from the Phase 3 program is expected to begin to be available in 2010.
About sanofi-aventis
About
Regeneron is a fully integrated biopharmaceutical company that discovers, develops, and commercializes medicines for the treatment of serious medical conditions. In addition to ARCALYST® (rilonacept) Injection for Subcutaneous Use, its first commercialized product, Regeneron has therapeutic candidates in clinical trials for the potential treatment of cancer, eye diseases, inflammatory diseases, and pain, and has preclinical programs in other diseases and disorders. Additional information about Regeneron and recent news releases are available on Regeneron's web site at www.regeneron.com.
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Forward-looking statements are statements that are not historical facts.
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beyond the control of sanofi-aventis, that could cause actual results
and developments to differ materially from those expressed in, or
implied or projected by, the forward-looking information and statements.
These risks and uncertainties include among other things, the
uncertainties inherent in research and development, future clinical data
and analysis, including post marketing, decisions by regulatory
authorities, such as the
Forward Looking Statement -
This news release discusses historical information and includes
forward-looking statements about Regeneron and its products, development
programs, finances, and business, all of which involve a number of risks
and uncertainties, such as risks associated with preclinical and
clinical development of aflibercept, determinations by regulatory and
administrative governmental authorities which may delay or restrict
Regeneron’s ability to continue to develop or commercialize aflibercept,
competing drugs that are superior to aflibercept, uncertainty of market
acceptance of aflibercept, the potential for any collaboration
agreement, including Regeneron’s agreements with the sanofi-aventis
Group and
Source:
Regeneron:
Peter Dworkin
Investor Relations
914.345.7640
peter.dworkin@regeneron.com
or
Laura
Lindsay
Media Relations
914.345.7800
laura.lindsay@regeneron.com
or
sanofi-aventis:
Salah
Mahyaoui
Media Relations
+33 1 53 77 40 31
salah.mahyaoui@sanofi-aventis.com
or
Sebastien
Martel
Investor Relations
+33 1 53 77 45 43
sebastien.martel@sanofi-aventis.com
or
Philippe
Zeisser
Investor Relations
+33 1 53 77 41 86
philippe.zeisser@sanofi-aventis.com