SangStat Medical Corp. has launched its long-awaited assault against Novartis Pharmaceutical Corp.'s cyclosporine franchise, pitting its SangCya product against Novartis's Sandimmune and newer Neoral formulations in the estimated $550 million U.S. market for the immunosuppressive agent.

SANG (Menlo Park, Calif.) last week began selling SangCya through its own sales force of 16 reps targeted at transplant physicians. The primary hurdles to adoption of SangCya, which is bioequivalent to Neoral, include its liquid formulation (versus Neoral's dominant capsule formulation) and physician resistance to changing drugs for stable patients.

But conversations with transplant physicians also indicate that SangCya's lower price and the potential for improved compliance with its CycloTech delivery device will assure the product a place in the transplant armamentarium.

SANG's strategy for enticing transplant physicians to switch patients to SangCya includes pricing 20 percent below Neoral; the CycloTech dispensing device; and data from clinical trials in a variety of patient populations that demonstrate SangCya's bioequivalence to Neoral.

The company also is conducting a clinical trial of SangCya and CycloTech designed to demonstrate a clinical benefit of using the device to improve patient compliance (see BioCentury Extra, Nov. 3). Initial results are expected at the end of 1999.

One challenge that SangCya will face is the unpopularity of liquid medication versus capsules. Indeed, Novartis spokesperson Mark Hill argued that SangCya's liquid form will blunt any challenge to the Novartis franchise. Thus, although a liquid formulation of Neoral exists, "liquid formulations only account for 5 to 7 percent of the market - the vast majority of patients take capsules," he said.

Although 5 percent of the U.S. market is not trivial at some $27 million, SANG Chairman and CEO Philippe Pouletty said the company is developing a capsule version of SangCya that it expects to put on the market by mid-2000. In the meantime, he said, SangCya will be able to compete against capsules because it is not an oily formulation like liquid Neoral, and because CycloTech makes dispensing a dose easier and more accurate than dosing of liquid Neoral.

Neoral is a microemulsion, a mixture of oil and water that is stabilized with surfactants. The cyclosporine is contained in oil droplets 10 to 100 millimicrons in diameter, which allows it to be absorbed more quickly with less dependence on diet and bile flow than a macroemulsion such as its first generation Sandimmune product.

SangCya is a microdispersion, which does not use oils to form droplets but instead forms nanoparticles in solution that are readily absorbed in the gut, Pouletty said. SANG has two patents covering its formulation.

Novartis also plans to reinforce the reluctance of physicians to switch the drugs for patients who are thriving with Neoral. The pharma company will argue in its sales pitches that cyclosporine is a critically dosed drug - meaning it has a very narrow therapeutic window. Too small a dose and the transplanted organ may be rejected, while too high a dose can result in adverse drug reactions such as nephrotoxicity and hypertension.

Despite the FDA's determination that SangCya is bioequivalent, Hill said the pharma company is "concerned that this new product is not 100 percent bioequivalent and that it may create problems for patients. We believe that patients should be informed of any switch in medication."

Chasing new patients

Novartis may face a tougher challenge from SANG in the market for new patients. Because SangCya has an AB rating from the FDA, pharmacists are able to substitute it for Neoral without a physician's permission.