BioWorld International Correspondent
Shares in Speedel were down by 14.4 percent Tuesday on news that the company had halted a pivotal Phase III trial of the selective endothelin receptor antagonist (ERA) SPP301 (avosentan) in diabetic nephropathy, following the development of excessive fluid retention in patients receiving the drug.
The stock on Tuesday closed at CHF165.30 on the Swiss Stock Exchange in Zurich.
Jessica Mann, medical director at Basel, Switzerland-based Speedel, told BioWorld International that the patients need to be followed up for four weeks before the study can be closed and its findings analyzed in greater detail.
"Fluid overload is a manifestation of either cardiac, pulmonary or renal dysfunction," she said. Its seriousness can vary. "It depends a little on what the context is."
The so-called ASCENT (Avosentan on Doubling of Serum Creatinine, End Stage Renal Disease and Death in Diabetic Nephropathy) trial, which began July 2005, was to have examined the impact of SPP301 on morbidity and mortality in more than 2,000 patients. (See BioWorld International, July 13, 2005.)
The company recently said it was on track to have recruited between 55 percent and 60 percent of the total by the end of this year, and it had aimed to launch the compound in 2010.
Fluid retention rates ranging from 6.9 percent to 12.1 percent were detected in a Phase II trial of the compound, said Speedel's director of communications and investor relations, Nick Miles. "It's a well known class effect but it wasn't at a level that gave us a cause for concern."
Two other ERAs, Tracleer (bosentan), which is marketed by Allschwil, Switzerland based Actelion Ltd. for pulmonary arterial hypertension, and darusentan, which Foster City, Calif.-based Gilead Sciences Inc. is developing for the same indication, have higher rates of edema, he said.
The company has several avenues to explore concerning the elevated fluid retention effect seen in the ASCENT trial. "Concomitant medication is certainly something we will look into," Mann said. Some of the patients participating in the trial also had more severe illness than those in the earlier study, and the treatment duration was considerably longer. Diuretics can potentially be used to control edema, but their use "varies a lot from country to country," Mann said.
However, Speedel is by no means halting the development program. It plans to spend six months examining the study data and developing plans for a new study design in diabetic nephropathy, as well as pursuing possible alternative indications. "The data safety monitoring board and the steering committee have both emphasized their confidence in the potential of the drug," Miles said. "This is not a dead compound."
Around 80 percent of diabetic nephropathy patients die before they reach end-stage renal disease, Mann said. In the Phase II trial, SPP301 caused an additional 30 percent reduction in proteinuria (excessive protein in the urine), a predictor of kidney damage, which prompted the FDA to grant the drug fast-track status. "It would be a pity to let it go to waste and not use it in the appropriate patient population," Mann said.