Impax To Ramp Up Sales Team, Diversify From Generics After Positive IPX066 Data

Impax plans to file an NDA for IPX066 for Parkinson's disease in the fourth quarter; the drug is partnered with GlaxoSmithKline outside the U.S.

Impax Laboratories Inc. is gearing up to launch its first brand product -an extended-release carbidopa-levodopa product for Parkinson's disease known as IPX066 - after releasing positive top-line data from a second Phase III trial.

IPX066 is the lynchpin of the Hayward, Calif. company's strategy to expand its branded pharmaceuticals unit, Impax Pharmaceuticals, and diversify its business mix beyond generic drugs, for which Impax is better known.

Impax plans to file an NDA for IPX066 through the 505(b)(2) regulatory pathway in the fourth quarter and launch the drug in the U.S. in 2012 using its own sales team. The firm recently signed GlaxoSmithKline PLC as a partner for IPX066, giving the U.K. drug maker rights to the product outside the U.S. and Taiwan in exchange for $11.5 million upfront, $175 million in potential milestones and tiered, double-digit royalties on sales (Also see "GSK Seeks Re-Entry To Parkinson's Market In Deal With Impax" - Pink Sheet, 16 Dec, 2010.).

"Our vision is that in about six years, operating profit from our generic and the brand business will be more evenly weighted," CEO Larry Hsu said during a March 15 conference call, outlining the Phase III data results. The company's strategy calls for advancing its internal R&D pipeline, but also buying an additional product to market through an acquisition or in-licensing arrangement, he added. Many generics firms, large and small, have adopted similar strategies by seeking to diversify their portfolios into branded drugs to protect against fluctuations inherent in their industry, some more successfully than others.

While IPX066, if approved, would be the first brand drug Impax has developed and brought to market, the company does market Pfizer's Lyrica (pregabalin) to neurologists through a co-promotion agreement. The company's CNS sales force currently is about 66 people strong and will be expanded to support the new drug launch. Impax Pharmaceuticals President Michael Nestor estimated the company will need a force of about 110 reps to sufficiently reach high-prescribing neurologists in the U.S.

Ahead of the conference call on March 14, Impax released positive top-line data from a Phase III trial, ADVANCE-Parkinson's Disease, showing that IPX066 significantly improved motor symptoms compared to immediate-release CD-LD in advanced Parkinson's patients experiencing motor fluctuations on multiple clinical measures. It is the second of two pivotal studies intended to support the NDA filing.

The company already released positive data from the APEX-PD trial in early Parkinson's disease, comparing IPX066 to placebo. A third trial, comparing the drug to CD-LD and entacapone, a combination currently marketed as Stalevo by Orion Corporation and Novartis AG, is currently enrolling patients.

Positive Comparative Data Relative To The Gold Standard

In the ADVANCE-PD study, IPX066 demonstrated a 37% improvement from baseline in "off time" during waking hours, the primary endpoint of the study, compared to a 17% improvement from baseline with the immediate-release version. "Off time" is the time when a patient's medication effect has worn off and there is a return of Parkinson's symptoms.

The study enrolled 471 patients on a stable regimen of IR CD-LD who were entered into a dose-adjustment phase of their medication, followed by a conversion to IP066 after which they were then randomized to either IPX066 or IR CD-LD. Those who converted to IPX066 experienced a reduction from baseline of more than two hours in total "off time" during waking hours. In comparison, patients in the IR group achieved similar improvement during their conversion to IPX066, but "off time" worsened by one hour during the double-blind treatment with IR CD-LD.

IPX066 was generally well-tolerated, with an adverse event rate of 43% during the double-blind portion of the study compared to 40% for IR CD-LD.

Given Generics, A Challenging Marketing Proposition

Despite the efficacy benefit, the marketing proposition for IPX066 won't be straightforward. Generic versions of the gold standard IR CD-LD and a controlled-release formula, widely known under the brand names Sinemet and Sinemet CR, are available, which will make selling IPX066 at a "premium price" as management said it intends to, more challenging.

Nonetheless, Robert Hauser, MD, the director of the Parkinson's Disease & Movement Disorders Center at the University of South Florida, said during the conference call that there is an opportunity for IPX066. One of the challenges with the existing IR formula is that the duration of benefit becomes shorter and shorter over time, so that patients' progress from taking three doses a day to many more.

"We're increasing levodopa IR from four times a day to five times a day, we're adding adjunctive medication and yet many patients still are experiencing a very substantial amount of 'off time' through the day," Hauser maintained. He suggested IP066 likely would be used most frequently by patients who are on the IR formula and start fluctuating, roughly about 30% of Parkinson's disease patients.

"I think that will be a commonly adopted practice, rather than going to four or five times a day of the levodopa IR and starting to add on a number of adjunctive medications," he said. As for the CD-LD controlled-release version, Hauser said, that is generally used at night rather than during the day because it takes about 40 minutes to start working as opposed to 20 minutes for the IR formula.

Collins Stewart analyst Louise Chen called the data "great news for Impax since IPX-66 diversifies the company's revenue away from solely generics." She estimates the drug could generate peak annual sales of $200 million to $400 million in the U.S., with a similar market opportunity ex-U.S. However, she cautiously forecast sales of just $90 million for IPX066 in 2016.

-Jessica Merrill ([email protected])