Washington Editor

MGI Pharma Inc. remains on schedule to file for FDA approval of Aquavan (fospropofol disodium) later this year after a pivotal study of the sedative product in patients undergoing bronchoscopy met its primary endpoint, corroborating previously reported findings in colonoscopy patients.

As a result, there's "not a lot of surprise" in the latest data, said Dhesh Govender, an analyst with Monness, Crespi, Hardt & Co. Inc. in New York. "The drug works the same way, whether it's in the colon or the bronchial tubes," he told BioWorld Today, anesthetizing nerve endings like existing standards of care in that setting.

But the principal differences for Aquavan are its quick onset of action, fast recovery period for patients following short surgical and diagnostic procedures, and ease of administration compared to the older products, namely the generic drugs propofol and midazolam, according to a research note from Joel Sendek, of Lazard Capital Markets LLC in New York, and those improvements "should provide a competitive advantage" over the currently marketed options.

A note from Chris Raymond, of Robert W. Baird & Co. in Chicago, revealed consensus sales estimates of $31 million for next year and $68 million in 2009.

Govender predicted peak sales of $120 million in three years, assuming Minneapolis-based MGI's small hospital sales force gets the FDA's OK to operate with a broad label in terms of touting Aquavan's aforementioned improvements over existing standards of care in that setting, as well as its better-tolerated profile. "Labeling is the key," he said.

But Raymond expressed a measure of caution, given FDA conservatism these days, noting that question marks linger on the potential label that could affect the drug's market uptake. In particular, it's important for the product to have a label that doesn't mandate monitored anesthesiology care, or MAC, which would limit uptake because an anesthesiologist's presence would be required in any procedure using Aquavan.

However, Govender indicated a minimal likelihood of that kind of restrictive labeling, given that it's a prodrug of propofol. He said he's "almost 100 percent certain" that a MAC label wouldn't get slapped on Aquavan, noting its minor differences from propofol.

The most recent Phase III trial produced an 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 who received a control bolus dose of 2 mg/kg of Aquavan (p<0.001). Sedation success was defined by patients achieving three consecutive scores of less than or equal to 4 on the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale after administering the sedative, and completion of the bronchoscopy procedure without the use of alternative sedatives and without manual or mechanical ventilation. The study allowed a limited number of supplemental doses of midazolam to be administered to maintain sedation during the procedure.

The primary endpoint success was mirrored by success in all the study's secondary endpoints. The treatment success rate among patients treated with the higher Aquavan bolus dose was 91.3 percent compared to 41.2 percent for control (p<0.001), and of those patients in the 6.5 mg/kg arm, 94.6 percent indicated that they would be willing to be treated again with the same sedative dose, compared to 78.2 percent of those in the control arm (p<.001 additionally percent of patients in the mg arm said they did not recall being awake during procedure compared to control group class="text">A total of 252 patients were randomized to the double-blind study's two arms. In addition to the efficacy findings, the results also showed that the 6.5 mg/kg dose's safety profile was predictable and similar to the 2 mg/kg dose.

Those bronchoscopy data, together with similar Phase III results in patients undergoing colonoscopy and an open-label study in patients undergoing minor surgical procedures, will serve as the basis of a new drug application to be filed early in the third quarter. The colonoscopy trial produced an 86.7 percent sedation rate in those in the 6.5 mg/kg group compared to 25.5 percent among those who received 2 mg/kg (p<0.001), and the open-label study demonstrated Aquavan's safety and tolerability at 6.5 mg/kg in a variety of settings such as arthroscopy, bunionectomy, dilation and curettage, endoscopy, hysteroscopy, lithroscopy, shunt placement and trans-esophageal echoes.

More than 40 million such procedures require moderate sedation every year in the U.S., according to a release by the company, whose management did not return calls seeking comment.

On Tuesday, MGI's stock (NASDAQ:MOGN) gained 9 cents to close at $21.09.