The regulatory approval horizon appears closer than ever for the kidney disease drug Fosrenol.

AnorMED Inc. said its licensee, Shire Pharmaceuticals Group plc, received an FDA approvable letter for Fosrenol (lanthanum carbonate). Shire, which continues to forecast a U.S. launch before the end of this year, said it would provide further updates on the time line down the road. Shire is initiating discussions with the agency to determine what needs to be clarified pre-approval as opposed to post-approval.

"They are not changing their guidance, so I have to take that as being relatively positive," AnorMED President and CEO Michael Abrams told BioWorld Today. "We're very excited about this. To us, it's not a matter of if, it's now a matter of when for this drug."

According to Vancouver, British Columbia-based AnorMED, the approvable letter asks for additional data and analysis to address a number of undisclosed questions. Abrams said further clarification on such issues could also be a boon for European approval of the drug, which has been delayed. Shire, which in 1996 gained an exclusive worldwide license to develop, manufacture, use and sell the drug, had expected European marketing approval in the second quarter of last year before long-term safety questions were raised.

"They are expecting the European review to last into the second half of this year, but they feel that the issues can be addressed with the existing data set," Adams said.

In May Shire submitted its U.S. new drug application for the drug, previously called Foznol, which is designed to treat high phosphate levels in the blood that occur in patients undergoing dialysis as a result of chronic kidney failure. Its Phase III program began in January 1999.

Andover, UK-based Shire assumed all responsibility and costs for Fosrenol's development and commercialization after licensing it from AnorMED. In all clinical trials to date, Abrams said the drug has been tested in more than 1,700 patients, among whom 154 have used it for more than two years and 46 have taken it for more than three years. Upon approval, AnorMED would receive a single-digit royalty on the net sales of the compound. Shire also has applied for regulatory approval in Canada, while development continues in Japan.

The company estimates up to 269,000 U.S. dialysis patients, among whom as many as 80 percent develop hyperphosphatemia and need treatment with a phosphate binder such as Fosrenol. Left untreated, hyperphosphataemia can lead to renal osteodystrophy, which causes bone pain, skeletal deformities and can result in fractures, while other research links the condition with the development of cardiovascular disease.

AnorMED reported at the American Society of Nephrology meeting in November that Fosrenol is effective in reducing high phosphate levels associated with end-stage renal disease and also reduces hypercalcemia. More specific results were released more than a year before, at the 2001 World Congress of Nephrology in San Francisco. Data demonstrated that 59 percent of treated patients achieved serum phosphate control vs. 23 percent of placebo patients (p=0.001). (See BioWorld Today, Oct. 17, 2001.)

"Fosrenol is a chewable, tasteless tablet that can be taken without water," Abrams said. "Dialysis patients are on limited fluid intake, so you don't have to use up part of your fluid allotment by swallowing your phosphate binder pills."

Fosrenol would operate in a market that already contains calcium- and aluminum-based therapies, as well as Renagel, a drug that belongs to Cambridge, Mass.-based Genzyme Corp. Abrams said lanthanum, Fosrenol's active ingredient, possesses a high affinity for phosphate and is minimally absorbed into the body. At the same time, the drug is devoid of calcium and aluminum, so it does not pose the threat of elevated calcium levels in the blood or the danger of dialysis dementia, which is associated with aluminum products.

On its own, AnorMED is developing chemokine receptor inhibitors that block CXCR4. Its lead molecule, AMD 3100, is in Phase II trials for stem cell transplantations in cancer patients. Abrams said AnorMED is working to file during the first half of this year an investigational new drug application for an oral CXCR4 inhibitor, AMD 070, an anti-HIV drug that blocks viral entry.

He said the company expects to partner both AMD 070 and AMD 473, a cancer drug originally partnered with London-based AstraZeneca plc. In November 2001, the pharmaceutical firm returned the compound to AnorMED after advancing the drug through Phase II trials. Two months before, AstraZeneca's news that it planned to re-evaluate its further development of the platinum-based anticancer agent dropped AnorMED's stock by C$5.90, or about 55 percent. (See BioWorld Today, Sept. 4, 2001.)

AnorMED's shares (TSX:AOM) rose C56 cents on Monday, or 23.5 percent, to close at C$2.94.