Final Phase IIb results of Speedel AG's endothelin-A receptor antagonist, SPP301, showed that the compound reduces proteinuria when administered on top of standard therapy for the treatment of diabetic nephropathy, confirming top-line results reported earlier this year.

Data presented at the 38th annual meeting of the American Society of Nephrology (ASN) in Philadelphia demonstrated that at all doses SPP301 decreased the rate of proteinuria, also known as urinary albumin, excretion compared to placebo, with the two highest doses of 25 mg and 50 mg recording the greatest reduction. SPP301 also cut total cholesterol over placebo.

"Most importantly, in about 55 percent of our patients, the proteinuria reduction was over 30 percent, which is the magic number as far the National Kidney Foundation is concerned," said Nick Miles, director of communications and investor relations at Basel, Switzerland-based Speedel.

That 30 percent is on top of the standard therapy involving angiotensin converting enzyme (ACE) inhibitor, he added. "To achieve that is very encouraging. It demonstrates that [the drug] could have a potential impact on morbidity and mortality."

A total of 286 patients were enrolled in the 12-week study. Speedel initially reported top-line results in March, and Miles said further analysis of the overall data showed "the same sort of message in terms of efficacy and safety."

In fact, the Phase II results were so promising that Speedel opted to move into pivotal trials without seeking a development partner to share the costs.

"We decided to take it into Phase III on our own," Miles told BioWorld Today, partly because "the data were so encouraging" and partly because of "the strong feedback we got from both the FDA and the [European Medicines Evaluation Agency] about the unmet medical need."

Diabetic nephropathy, which refers to any harmful effect on kidney structure or function due to diabetes mellitus that ultimately can progress to end-stage renal disease, is estimated to affect about 8 million people diagnosed with diabetes in the U.S., Europe and Japan.

After securing a special protocol assessment from the FDA, Speedel starting recruiting patients for its Phase III study in July. Miles said the target is to enroll more than 2,000 patients at 250 sites, and "our goal is to have 75 percent of recruitment completed by the end of 2006." (See BioWorld Today, July 8, 2005.)

Speedel anticipates the trial taking about three and a half years, with data being presented in the first half of 2009. Since the compound has received fast-track designation by the FDA, approval and launch of the drug could occur during the second half of 2009.

The once-daily, oral SPP301 is a second-generation endothelin-A receptor antagonist (ERA) licensed from Basel, Switzerland-based F. Hoffmann-La Roche Ltd. Speedel holds exclusive worldwide development and commercialization rights.

Though the ERA mode of action has been successful against other diseases, such as pulmonary arterial hypertension, Speedel's drug is the first ERA to be developed specifically for diabetic nephropathy. It also is one of only a few drugs in late-stage development for treating that indication.

Another is Keryx Pharmaceuticals Inc.'s KRX-101 (sulodexide gelcaps), in a Phase III study to treat Type II diabetic nephropathy patients with persistent microalbuminaria. The New York-based company also presented its final Phase II results at the ASN meeting, showing that 200 mg of KRX-101 demonstrated statistically significant advantages over placebo. The primary endpoint for the Phase III trial is the percentage of patients at the end of the trial who achieve "therapeutic success," defined as either a 50 percent reduction in albumin to creatinine (ACR) ratio or normalization of ACR, with a least a 25 percent reduction in ACR. (See BioWorld Today, March 17, 2005.)

Shares of Keryx (NASDAQ:KERX) lost 8 cents Monday to close at $14.86.

Earlier-stage products to treat diabetic nephropathy are in development by South San Francisco-based Exelixis Inc., which is nearing Phase II with XL784, an inhibitor of ADAM-10 metalloprotease enzyme, and FibroGen Inc., also of South San Francisco, which is in Phase Ib testing with its fully human monoclonal antibody, FG-3019, designed to mediate connective tissue growth factor. That drug also is in development to treat idiopathic pulmonary fibrosis and pancreatic cancer.

In other news from ASN:

Acologix Inc., of Hayward, Calif., presented recent study results of Phosphatonin, its product candidate for the treatment of hyperphosphatemia associated with renal disease, characterizing the in vitro and in vivo activities of the molecule, also known as MEPE and AC-2000) in phosphate regulation. The company said this is the first reported expression of recombinant human MEPE (rhMEPE) in a mammalian expression system, and it suggests significant differences in posttranslational modifications compared to those observed in rhMEPE expressed by E. coli or baculovirus systems.

Anadys Pharmaceuticals Inc., of San Diego, presented Phase I results of its isatoribine prodrug, ANA975, showing it to be well tolerated at all doses investigated, with no serious adverse events. In the trial, 38 healthy subjects received a single, oral dose administered as a 5 mg/mL solution in the fasted states at doses of either 400 mg, 800 mg or 1,200 mg. ANA975 was converted rapidly and extensively to isatoribine, with maximum concentration typically occurring within one hour after dosing. The company reported that definitive conclusions regarding product safety and tolerability will be determined following future trials of longer duration. Anadys is developing ANA975, a small molecule Toll-like receptor agonist, in collaboration with Basel, Switzerland-based Novartis AG for chronic hepatitis C virus, and other potential infectious disease indications.

FibroGen Inc., of South San Francisco, presented data from ongoing dose-escalation studies of FG-2216 in anemic patients with chronic kidney disease showing that patients not previously treated with recombinant erythropoietin (EPO) therapy on average exhibit significantly increased levels of hemoglobin in response to the low dose of GF-2216 administered orally three times a week for four weeks. Early results from the 10 mg/kg dose group demonstrate a mean increase of 2.7 g/dL Hb in patients dosed twice a week for four weeks. A second study is evaluating the ability of GF-2216 therapy to maintain Hb levels in patients following discontinuation of recombinant EPO therapy. The company also presented data on FG-4592, designed for treatment of anemia of chronic disease, showing that the drug reduced abnormally high levels of hepcidin back to normal levels, and restored the natural balance of iron regulation in an experimental model of inflammation-induced anemia. FG-4592 is in Phase I testing.

RenaMed Biologics Inc., of Lincoln, R.I., reported positive preliminary findings from a Phase II study of its Renal Bio-Replacement Therapy to treat patients with acute renal failure. The study of 58 patients found that RenaMed's therapy at 28 days increased survival rate by 72 percent, and the trend in improved survival was sustained through 90 and 180 days. Renal Bio-Replacement Therapy is designed to replace lost kidney functions in patients with acute renal failure, using physiologically active human renal epithelial cells incorporated in a hollow fiber cartridge and administered outside of the body.