As expected, MGI Pharma Inc. filed a new drug application for Aquavan, its sedative-hypnotic agent in patients undergoing minor surgical or diagnostic procedures, and pending approval, anticipates launching the product in the third quarter of 2008.

"It's a great milestone for us," said Tim Smith, senior director of investor relations for the Minneapolis-based firm. "It's another step as we continue expanding our product portfolio," which already boasts five marketed products, including Aloxi (palonosetron hydrochloride) injection for the prevention of chemotherapy-induced nausea and vomiting, Dacogen (decitabine) for myelodysplastic syndromes and Gliadel Wafer (polifeprosan 20 with carmustine implant) for treating high-grade malignant gliomas as an adjunct to surgery and radiation.

MGI is seeking a broad label for Aquavan (fospropofol disodium). A prodrug of propofol, Aquavan is designed to provide quick onset of sedation, allow for fast, clear-headed recovery and be easily administered, all of which MGI hopes will give the drug an edge over the leading generics such as propofol and midazolam in the sedation market. More than 40 million short diagnostic and therapeutic procedures are performed in the U.S. annually, and about half of those involve gastrointestinal procedures. The company intends to focus on that GI market initially, Smith said, and later expand into other areas, such as cardiovascular and emergency room procedures and other minor surgeries.

The drug's commercial potential likely will depend on whether it gets the FDA's blessing for use without monitored anesthesia care (MAC) sedation. MAC requires the added presence of an anesthesiologist and, therefore, would limit Aquavan's market uptake. Though MGI successfully completed four trials in patients undergoing colonoscopies, bronchoscopies and minor surgical procedures without MAC sedation, analyst Christopher Raymond, of Chicago-based Robert W. Baird & Co., remains cautious. He wrote in a research note that "approval without a MAC label may not be completely straight forward, given a more safety conscious FDA."

MGI, however, is not anticipating MAC restrictions. "We had extensive discussions with the FDA" when designing the pivotal Phase III studies, none of which included oversight by anesthesiologists, Smith said.

Data from the NDA included results from a Phase III bronchoscopy trial, reported in March, showing a 88.7 percent sedation rate among patients who received an initial bolus dose of 6.5 mg/kg of Aquavan compared to 27.5 percent of patients in the control arm who received 2 mg/kg of Aquavan, as determined by three consecutive scores of 4 or less on the Modified Observer's Assessment of Alertness/Sedation scale. Secondary endpoints from the 252-patient study showed that, of those receiving the 6.5 mg/kg Aquavan arm, 94.6 percent indicated that they would be willing to be treated again with the same sedative dose, compared to 78.2 percent in the control arm, and that 83.3 percent of patients in the 6.5 mg/kg arm said they did not recall being awake during the procedure vs. 55.4 percent in the control group. (See BioWorld Today, March 21, 2007.)

Those data mirrored similar Phase III results from patients undergoing colonoscopy, as well as results from an open-label study in minor surgical procedures. The colonoscopy trial showed a sedation rate of 86.7 percent for patients receiving 6.5 mg/kg of Aquavan compared to 25.5 percent in the control arm, and the open-label trial demonstrated the product's safety and tolerability in several different settings, such as arthroscopy, dilation and curettage, hysteroscopy, lithroscopy, shunt placement and transesophageal echocardiograms.

Upon Aquavan's approval by the FDA, MGI anticipates marketing the drug to the acute care market, and plans to start building a new sales force at the end of this year or early next year. Smith told BioWorld Today that a team will be in place to market Aloxi.

MGI and partner Helsinn Healthcare SA, of Lugano, Switzerland, filed a supplemental NDA for Aloxi that includes the removal of a dosing restriction for prevention of chemotherapy-induced nausea and vomiting. The PDUFA date for that application is March 4, 2008, "so we'll have [the sales team] in place by then," he said.

MGI is projecting that Aquavan could be a $400 million opportunity for the company, Smith said, if the drug can gain a 35 percent share of the GI procedure market and a 30 percent share of the remaining minor surgery and diagnostic procedure sedation space.

The company expects to be notified by the FDA within 60 days on the acceptability of its application, which would be given the standard review of 10 months from filing.

While awaiting the FDA's decision on Aquavan, MGI will continue focusing on its development pipeline, which includes late-stage studies of Dacogen in acute myeloid leukemia and for alternate dosing in myelodysplastic syndromes, as well as a mid-stage thrombocytopenic drug, AKR-501, recently picked up from Paramus, N.J.-based AkaRx Inc. That deal called for MGI to pay $45 million up front, with an option to acquire AkaRx for $255 million at any time before Jan. 8, 2010. (See BioWorld Today, Aug. 30, 2007.)