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.