Data from the phase 3 bronchoscopy trial, together with the results from a phase 3 trial in patients undergoing colonoscopy and an open-label study in patients undergoing minor surgical procedures, will form the foundation of the Aquavan New Drug Application (NDA). MGI PHARMA plans to submit the Aquavan NDA to the U.S. Food and Drug Administration (FDA) early in the third quarter of 2007. As is consistent with standard medical practice, the three trials comprising the Aquavan pivotal program were conducted without monitored anesthesia care (MAC) sedation, and study drugs were administered by medical personnel as dictated by local investigative site guidelines.
"With more than 40 million procedures per year in the U.S. requiring moderate sedation, Aquavan may address a significant market opportunity," said Lonnie Moulder, President and Chief Executive Officer of MGI PHARMA. "The results of this pivotal program, together with completed pharmacokinetic studies, indicate that Aquavan has a pharmacokinetic and pharmacodynamic profile which may facilitate achievement and maintenance of targeted, controlled sedation by proceduralists. This unique profile may allow pati ents to recover more quickly following short surgical and diagnostic procedures and could improve facility and physician practice efficiency."
Bronchoscopy Pivotal Trial Results
A randomized, double-blind, multi-center phase 3 study was conducted to determine the safety and efficacy of Aquavan for the sedation of patients undergoing flexible bronchoscopies. Patients enrolled in this trial had medical histories that included respiratory disorders (88%), vascular disorders (55%), metabolism and nutrition disorders (55%), and infections (52%). Of all patients enrolled in the trial, 62% were found to have a pulmonary or respiratory abnormality at screening including 52% with chronic obstructive pulmonary disease (COPD) and 20% with a lung mass.
A total of 252 patients were randomized and received either a control dose of 2.0 mg/kg Aquavan or a 6.5 mg/kg dose of Aquavan. Following administration of the initial bolus dose of the study drug, the design of this trial allowed a limited number of supplemental doses to be administered to maintain sedation during the procedure.
The primary endpoint of this trial was sedation success, defined as a patient having achieved three consecutive Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scores of less than or equal to 4 after administration of sedative medication and completion of the bronchoscopy procedure without the use of alternative sedative medication and without manual or mechanical ventilation. The secondary endpoint of treatment success was defined as completion of the procedure without the use of alternative sedative medication and without manual or mechanical ventilation. Additional endpoints included measures of patient satisfaction.
Among patients treated with an initial bolus dose of 6.5 mg/kg (n=150) of Aquavan, the sedation success rate was 88.7% compared to 27.5% of patients in the control arm (n=102) (p less than 0.001). The treatment success rate among patients t reated with the initial bolus dose of 6.5 mg/kg Aquavan was 91.3% compared to 41.2% for control (p less than 0.001). Of those patients in the 6.5 mg/kg Aquavan arm, 94.6% indicated that they would be willing to be treated again with the same sedative dose, compared to 78.2% of those in the control arm (p less than 0.001). Additionally, 83.3% of patients in the 6.5 mg/kg Aquavan arm reported that they did not recall being awake during the procedure, compared to 55.4% for control (p less than 0.001).
The nature and frequency of sedation-related adverse events were similar between patients who received the Aquavan 6.5 mg/kg dose and those in the control arm, and were predictable for this patient population. Based upon the American Society of Anesthesiologists (ASA) Physical Status Classification System, 52% of patients in this study were classified as P2 (having mild systemic disease such as asthma, obesity or diabetes mellitus), 37% were P3 (having severe systemic disease such as cardiovascular disease that limits activity or severe diabetes with systemic complications), and 6% were P4 (having systemic disease that is a constant threat to life, such as unstable angina pectoris, myocardial infarction, or cerebrovascular accident within the past six months). The most frequently observed sedation-related adverse event in the two study arms was transient hypoxemia (defined as blood oxygen saturation levels less than or equal to 90% for more than 30 seconds at any point, as measured by pulse oximetry), which was observed in 15% of patients who received an initial bolus dose of 6.5 mg/kg of Aquavan compared to 13% of patients who received control. Eight patients (5%) who received 6.5 mg/kg Aquavan experienced hypotension. A single patient with ongoing severe hypoxemia and pneumonia, and a history of COPD, congestive heart failure, anemia and other severe comorbidities received manual ventilation support.
"The collective results of this pivotal program demonstr ate consistent results for the 6.5 mg/kg initial bolus dose of Aquavan and describe a predictable and effective therapeutic sedation profile in patients with a wide range of heath status and comorbidities who are undergoing a variety of common procedures," said Mary Lynne Hedley, Ph.D., Executive Vice President and Chief Scientific Officer of MGI PHARMA. "We remain on track to submit the Aquavan NDA to the FDA early in the third quarter of this year."
Bronchoscopy Results Consistent with Previously-Reported Colonoscopy Data
The results of this study are consistent with the data previously reported from a pivotal phase 3 study of Aquavan in 312 patients undergoing colonoscopy. The primary endpoint of the colonoscopy trial was also sedation success, and additional endpoints included treatment success and measures of physician and patient satisfaction. In the colonoscopy trial, among patients treated with an initial bolus dose of 6.5 mg/kg of Aquavan, the sedation success rate was 86.7% compared to 25.5% among patients treated with an initial bolus control dose of 2.0 mg/kg of Aquavan (p less than 0.001). Based upon the ASA Physical Status Classification System, 31% of patients in this study were classified as P1 (having no known systemic disease), 65% were classified as P2, 4% were classified as P3, and none were classified as P4. One patient in this study experienced hypoxia after receiving midazolam subsequent to administration of a bolus dose of 6.5 mg/kg Aquavan, which resolved following verbal stimulation.
Minor Surgery Safety Study Results
A single arm, open label study was conducted in 123 patients undergoing a variety of minor surgical procedures to assess the safety and tolerability of Aquavan at a dose of 6.5 mg/kg in a variety of settings including arthroscopy, bunionectomy, dilation and curettage, endoscopy, hysteroscopy, lithroscopy, shunt placement and trans-esophageal echoes. Results of this study also describe a predictable safety profile. The most frequently observed sedation-related adverse event in this study was transient hypotension (3%). No adverse events led to procedure or study drug discontinuation.
About Aquavan(R) (fospropofol disodium) Injection
Aquavan(R) (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 sedation of patients undergoing short surgical or diagnostic procedures. Aquavan has not been approved for marketing by the U.S. Food and Drug Administration (U.S. FDA) or any other regulatory agencies.
About MGI PHARMA
MGI PHARMA, INC. is a biopharmaceutical company focused in oncology and acute care that acquires, researches, develops and commercializes proprietary products that address the unmet needs of patients. MGI PHARMA markets Aloxi(R) (palonosetron hydrochloride) Injection, Dacogen(R) (decitabine) for Injection, and Gliadel(R) Wafer (polifeprosan 20 with carmustine implant) in the United States. The Company directly markets its products in the U.S. and collaborates with partners to reach international markets. For more information about MGI PHARMA, please visit www.mgipharma.com.
This news release contains certain "forward-looking" statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements are typically preceded by words such as "believes," "expects," "anticipates," "intends," "will," "may," "should," or similar expressions. These forward-looking statements are not guarantees of MGI PHARMA's future performance and involve a number of risks and uncertainties that may cause actual results to differ materially from the results discussed in these statements. Factors that might cause MGI PHARMA's results to differ materially from those expressed or implied by such forward-looking statements include, bu t are not limited to, the ability of MGI PHARMA's product candidates to be proven safe and effective in humans, to receive marketing authorization from regulatory authorities, and to ultimately compete successfully with other therapies; continued sales of MGI PHARMA's marketed products; development or acquisition of additional products; reliance on contract manufacturing; changes in strategic alliances; continued access to capital; ability of MGI PHARMA to successfully complete the integration of Guilford with its existing operations; the risk that the perceived advantages of the Guilford transaction may not be achieved; and other risks and uncertainties detailed from time to time in MGI PHARMA's filings with the Securities and Exchange Commission including its most recently filed Form 10-Q or 10-K. MGI PHARMA undertakes no duty to update any of these forward-looking statements.
For MGI PHARMA, INC.
Jennifer Davis, 212-332-4381
Susan Silao, 212-332-4364