Hoping to expand its presence in the global marketplace, Nabi Biopharmaceuticals Inc. initiated a Phase IV study of a hyperphosphatemia product acquired last year.
The trial, called PRECISE, will evaluate the phosphate binder PhosLo (calcium acetate) with the statin Lipitor (atorvastatin calcium) in about 150 patients. The goal is to demonstrate the significance of using PhosLo plus Lipitor as a combination therapy to optimize cardiovascular health in end-stage renal disease patients.
"I think this is just one of several studies that we'll be initiating this year into early next year, which are going to position us to maximize opportunities for PhosLo, not only in the U.S. market, but to position it to be a significant product on a global basis," said Thomas McLain, chairman, CEO and president of Boca Raton, Fla.-based Nabi.
The double-blind, placebo-controlled study will randomize end-stage renal disease patients to receive PhosLo plus Lipitor, or PhosLo plus placebo. Lipitor, marketed by New York-based Pfizer Inc., is the world's most prescribed agent for reducing low-density lipoprotein.
The 150 patients will be spread throughout 15 study sites. The primary endpoint will be the measurement of cardiovascular calcification by electron beam computer tomography. Secondary endpoints include serum phosphate, calcium-phosphate product, lipid levels and how well the combination therapy is tolerated.
What researchers hope to find is evidence that PhosLo's control of hyperphosphatemia combined with the reduction of cholesterol levels produces a significant benefit by reducing the risk of developing cardiovascular complications. The trial also will determine the optimal treatment regimen for the combination therapy.
Nabi expects it will take six months to enroll all of the patients. They will be followed for 12 months, and preliminary data should be available by the end of this year. Cardiovascular calcification data are expected to be available at the end of 2005.
The company hopes that positive data from the trial will be presented at a number of scientific sessions, raising the awareness of physicians who would be more likely to prescribe PhosLo and Lipitor together.
"It will provide the clinical evidence that can be published and be part of how we market the product," McLain said.
Nabi does not have a regulatory strategy in conducting the Phase IV trial.
"We always would be able to submit the data as a supplement to the NDA and ask the FDA if we could get it on our label," said Henrik Rasmussen, senior vice president of clinical, medical and regulatory affairs at Nabi. "It's a possibility, but we didn't plan the study as a label supplement."
Nabi bought PhosLo last summer from Braintree Laboratories Inc., of Braintree, Mass., for $90 million in cash plus 1.5 million shares of stock. An article published last month in Kidney International highlighted clinical results that showed PhosLo is a superior regulator of serum phosphorus levels and the calcium-phosphorus product. The product was first approved in 1991 and is sold in tablet and gel-cap form for hyperphosphatemia - elevated levels of phosphate in the blood - in patients with end-stage renal disease. (See BioWorld Today, June 25, 2003, and July 15, 2003.)
McLain told BioWorld Today that PhosLo is expected to bring in U.S. sales of between $32 million and $35 million this year. The product also is approved, but not marketed, in Canada. Nabi will file for regulatory approval in Europe by the end of this year, starting a comparison trial early next year of calcium acetate and calcium carbonate, which is commonly used in Europe.
Cardiovascular disease is responsible for more than 50 percent of all deaths in end-stage renal disease patients. Researchers have found three important factors in improving the cardiac health of those patients: the level of phosphate in their blood, the calcium-phosphate balance and cholesterol levels. Nabi's PRECISE trial will provide new data on the combination of PhosLo plus a statin, and it could show that the combination therapy offers a lower cost than that of competitor Renagel, a product marketed by Genzyme Corp., of Cambridge, Mass.
McLain believes PhosLo will gain a greater market share as a result of conducting the Phase IV trials. In addition to the trial with Lipitor, which will evaluate patients on hemodialysis, PhosLo will enter another study later this year in chronic kidney disease patients pre-dialysis.
McLain said there are about 300,000 end-stage renal disease patients in the U.S., another 240,000 in Europe and 240,000 in Japan.
"As you can see, as we expand into new geographies the opportunities are very significant," he said.
Nabi's purchase of PhosLo complements its Phase III StaphVax product, which is designed to prevent the most dangerous and prevalent strains of Staph aureus bacterial infections.
PhosLo is one of four products the company markets. The others are Nabi-HB for hepatitis B, WinRho SDF for immune thrombocytopenic purpura and suppression of RH isoimmunization, and Aloprim for the management of patients with leukemia, lymphoma and solid-tumor malignancies. In addition to StaphVax, Nabi has other products in development, including the antibody Altastaph to prevent S. aureus infections, a nicotine vaccine NicVax, and Civacir, an antibody for preventing hepatitis C virus re-infection in liver transplant patients.