MGI PHARMA Provides Update on Aquavan(R) Injection Program
Wednesday December 21, 7:00 am ET
Top Line Results of Successful Phase 2 Dose Ranging Study Summarized
Aquavan(R) Injection Pivotal Program Planned to Begin in Early 2006
MINNEAPOLIS--(BUSINESS WIRE)--Dec. 21, 2005--MGI PHARMA, INC. (Nasdaq:MOGN - News), an oncology and acute care focused biopharmaceutical company, today announced top line results from a randomized, double-blind, multi-center phase 2 dose ranging study of Aquavan® (fospropofol disodium) Injection in patients undergoing colonoscopy. In addition, the Company provided an overview of the pivotal program that is intended to serve as a basis for registration of Aquavan Injection for use as a sedative in patients undergoing procedures requiring minimal to moderate sedation. This pivotal program is planned to begin in early 2006.
Phase 2 Dose Ranging Study
A phase 2 dose ranging study was conducted to determine the dose-response relationship of Aquavan Injection for endpoints of sedation success, patient satisfaction, investigator satisfaction, and safety. A total of 127 adults undergoing colonoscopy were randomized to receive one of four different initial bolus doses of Aquavan Injection (2.0, 5.0, 6.5, or 8.0 mg/kg) or midazolam (0.02 mg/kg) following pretreatment with fentanyl citrate. Following administration of the initial bolus dose of study drug, the design of this trial allowed supplemental doses to be administered to reach and maintain minimal to moderate sedation during the procedure. Study drugs were administered by medical personnel as dictated by local investigative site guidelines; administration by an anesthesiologist was not required.
The results of this dose ranging study show the 6.5 mg/kg and 8.0 mg/kg doses of Aquavan Injection were statistically superior to the 2.0 or 5.0 mg/kg bolus doses of Aquavan Injection with regard to the sedation success endpoint. In a blinded survey, investigators treating 92% of the patients receiving an initial bolus dose of 6.5 mg/kg indicated that they would again choose Aquavan Injection for procedures needing moderate sedation, compared to the responses of investigators administering the 8.0 mg/kg dose of Aquavan Injection (83%) or midazolam (77%).
Data from this study also indicate that patients treated with Aquavan Injection required fewer supplemental doses to achieve initial sedation compared to those who received midazolam. More than 90% of patients who received Aquavan Injection required two or fewer supplemental doses during initiation of sedation, compared to 58% of patients who were treated with midazolam.
Sedation Adequacy of
Initial Dose-Study Drug Success(a) Sedation(b)
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2.0 mg/kg Aquavan Injection 24% 28%
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5.0 mg/kg Aquavan Injection 36% 50%
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6.5 mg/kg Aquavan Injection 75% 89%
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8.0 mg/kg Aquavan Injection 95% 83%
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0.02 mg/kg midazolam 81% 58%
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(a) Sedation success was defined as three consecutive Modified
Observer's Assessment of Alertness/Sedation (MOAA/S) scores
greater than or equal to 4 after administration of sedative
medication, completion of the colonoscopy procedure without the
use of alternative sedative medication, and completion of the
colonoscopy procedure without manual or mechanical ventilation.
(b) Adequacy of sedation prior to initiation of the procedure was
determined by blinded investigator survey.
"The data from this phase 2 study clearly indicate a dose response for Aquavan Injection and describe a promising therapeutic profile," stated Lonnie Moulder, President and CEO of MGI PHARMA. "Aquavan Injection for minimal to moderate procedural sedation represents an excellent market opportunity for MGI PHARMA, as we continue to strengthen our acute care portfolio and advance our pipeline of late stage product candidates. We look forward to initiating a pivotal program for this product candidate in early 2006."
Various measures of patient satisfaction were also analyzed as a part of this study. Patients were surveyed to determine the time needed to resume normal activities and food intake. The time to resumption of normal activities and food intake was shortest for patients who received an initial dose of 6.5 or 8.0 mg/kg Aquavan Injection in comparison to midazolam. Patients treated with an initial bolus of 6.5 or 8.0 mg/kg of Aquavan Injection were able to resume normal activity at least 2 hours (greater than 50%) sooner and eat an hour (greater than 40%) sooner than those treated with midazolam. Of those patients who received an initial dose of 6.5 mg/kg or 8.0 mg/kg Aquavan Injection, 100% and 83%, respectively, indicated that they were adequately sedated during the procedure, compared to 89% of patients treated with midazolam. Overall, 92% of the patients who received the 6.5 mg/kg dose of Aquavan Injection indicated the highest levels of satisfaction with their experience, compared to 79% of patients treated with the 8.0 mg/kg dose of Aquavan injection and 69% of patients treated with midazolam.
No serious adverse events were reported and no adverse events led to procedure or study drug discontinuation during this trial. In addition, no patients in this study required manual or mechanical ventilation. The most common adverse events experienced were burning sensation and paraesthesia.
"We are encouraged that patients and investigators reported high levels of satisfaction with Aquavan Injection. Based on the sedation success outcomes combined with patient and investigator satisfaction survey results, we have decided to advance the 6.5 mg/kg dose of Aquavan Injection into a pivotal development program that will be designed to serve as the basis for FDA registration," said Mary Lynne Hedley, Sr. Vice President and Chief Scientific Officer of MGI PHARMA. "We plan to begin this program in early 2006 and expect that it will be completed within one year."
Pivotal Clinical Development Program
The pivotal development program for Aquavan Injection is expected to begin in early 2006 and will consist of two randomized, double-blind, multi-center phase 3 trials and an open label safety study. The first pivotal trial will enroll a total of 300 patients undergoing colonoscopy. The second pivotal study is planned to enroll 250 patients undergoing bronchoscopy. The endpoints of both pivotal trials include sedation and treatment success (as previously defined), patient satisfaction, investigator satisfaction, and measures of sedation adequacy, recovery, clinical benefit, and safety.
In addition to the two pivotal trials, an open label, multi-center safety study will be conducted in 150 patients undergoing minor procedures, including arthroscopy, bunionectomy, dilation and curettage, endoscopy, hysteroscopy, lithotripsy, shunt placement and trans-esophageal echoes. The goal of this study will be to assess the safety of a single dose of Aquavan Injection in a variety of minor surgical procedures.
MGI PHARMA anticipates that enrollment in these three clinical trials will conclude in approximately one year.
About Aquavan® (Fospropofol Disodium) Injection
Aquavan (fospropofol disodium) Injection, a proprietary water-soluble prodrug of propofol that after intravenous injection is rapidly converted by an enzyme (alkaline phosphatase) in the body into propofol, is a product candidate in development for minimal to moderate sedation. Aquavan Injection has not been approved by the FDA or any other regulatory agencies. MGI PHARMA plans to initiate a pivotal clinical development program for Aquavan Injection in early 2006. |
